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    Clinical Trial Results:
    A multicenter, randomized, double-blind, parallel group, active-controlled study to evaluate the efficacy and safety of LCZ696 compared to valsartan, on morbidity and mortality in heart failure patients (NYHA Class II-IV) with preserved ejection fraction

    Summary
    EudraCT number
    		 2013-001747-31
    Trial protocol
    		 SK   HU   AT   BG   DE   ES   NO   GB   NL   CZ   IT   SE   BE   DK   GR   FI   HR   PL   SI  
    Global end of trial date
    07 Jun 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Jun 2020
    First version publication date
    21 Jun 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CLCZ696D2301
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01920711
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Clinical Disclosure Office, 41 613241111, Novartis.email@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Jun 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jun 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to compare sacubitril/valsartan to valsartan in reducing the rate of the composite endpoint of cardiovascular (CV) death and total (first and recurrent) heart failure (HF) hospitalizations, in HF patients (NYHA Class II-IV) with preserved ejection fraction (LVEF ≥ 45%).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Jul 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 110
    Country: Number of subjects enrolled
    Australia: 24
    Country: Number of subjects enrolled
    Austria: 42
    Country: Number of subjects enrolled
    Belgium: 65
    Country: Number of subjects enrolled
    Brazil: 109
    Country: Number of subjects enrolled
    Bulgaria: 363
    Country: Number of subjects enrolled
    Canada: 79
    Country: Number of subjects enrolled
    China: 265
    Country: Number of subjects enrolled
    Colombia: 12
    Country: Number of subjects enrolled
    Croatia: 60
    Country: Number of subjects enrolled
    Czech Republic: 241
    Country: Number of subjects enrolled
    Denmark: 36
    Country: Number of subjects enrolled
    Finland: 8
    Country: Number of subjects enrolled
    France: 38
    Country: Number of subjects enrolled
    Germany: 388
    Country: Number of subjects enrolled
    Greece: 63
    Country: Number of subjects enrolled
    Guatemala: 47
    Country: Number of subjects enrolled
    Hungary: 252
    Country: Number of subjects enrolled
    India: 79
    Country: Number of subjects enrolled
    Israel: 83
    Country: Number of subjects enrolled
    Italy: 204
    Country: Number of subjects enrolled
    Japan: 79
    Country: Number of subjects enrolled
    Korea, Republic of: 48
    Country: Number of subjects enrolled
    Mexico: 60
    Country: Number of subjects enrolled
    Netherlands: 102
    Country: Number of subjects enrolled
    Norway: 14
    Country: Number of subjects enrolled
    Peru: 32
    Country: Number of subjects enrolled
    Philippines: 33
    Country: Number of subjects enrolled
    Poland: 180
    Country: Number of subjects enrolled
    Romania: 110
    Country: Number of subjects enrolled
    Russian Federation: 170
    Country: Number of subjects enrolled
    Serbia: 19
    Country: Number of subjects enrolled
    Singapore: 20
    Country: Number of subjects enrolled
    Slovakia: 310
    Country: Number of subjects enrolled
    Slovenia: 13
    Country: Number of subjects enrolled
    South Africa: 70
    Country: Number of subjects enrolled
    Spain: 254
    Country: Number of subjects enrolled
    Sweden: 41
    Country: Number of subjects enrolled
    Switzerland: 12
    Country: Number of subjects enrolled
    Taiwan: 61
    Country: Number of subjects enrolled
    Turkey: 23
    Country: Number of subjects enrolled
    United Kingdom: 123
    Country: Number of subjects enrolled
    United States: 480
    Worldwide total number of subjects
    4822
    EEA total number of subjects
    2907
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    830
    From 65 to 84 years
    3992
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 10, 359 patients were screened. 5747 patients were in the Enrolled set. 5746 patients entered valsartan run-in epoch, 5205 patients entered LCZ696 run-in epoch. 4822 patients who completed run-in were randomized at 755 sites in 43 countries. 2419 into the LCZ696 treatment group and 2403 into the valsartan treatment group.

    Pre-assignment
    Screening details
    		 10, 359 patients were screened. 5747 patients were in the Enrolled set. 5746 patients entered valsartan run-in epoch, 5205 patients entered LCZ696 run-in epoch. 4822 patients who completed run-in were randomized at 755 sites in 43 countries. 2419 into the LCZ696 treatment group and 2403 into the valsartan treatment group.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 LCZ696
    Arm description
    		 Single Blind Run-in Period (3-8 weeks): Prior optional valsartan run-in 40 mg bid for 1-2 weeks for some patients. followed by Valsartan 80 mg bid for 1-2 weeks followed by LCZ696 100 mg bid for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients could only be randomized from the run-in period if they met all of the run-in safety criteria. Target dose of LCZ696 during the double blind period was 200 mg bid
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sacubitirl/Valsartan
    Investigational medicinal product code
    LCZ696
    Other name
    Entresto
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg

    Investigational medicinal product name
    Sacubitirl/Valsartan
    Investigational medicinal product code
    LCZ696
    Other name
    Entresto
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg

    Investigational medicinal product name
    Sacubitirl/Valsartan
    Investigational medicinal product code
    LCZ696
    Other name
    Entresto
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg

    Investigational medicinal product name
    Sacubitril/Valsartan
    Investigational medicinal product code
    LCZ696
    Other name
    Entresto
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to match 50 mg, 100mg, 200 mg

    Arm title
    		 Valsartan
    Arm description
    		 Single Blind Run-in Period (3-8 weeks): Prior optional valsartan run-in 40 mg bid for 1-2 weeks for some patients, followed by Valsartan 80 mg bid. for 1-2 weeks followed by LCZ696 100 mg bid for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients could only be randomized from the run-in period if they met all of the run-in safety criteria. Target dose of Valsartan during the double blind period was 160 mg bid
    Arm type
    		 Experimental

    Investigational medicinal product name
    Valsartan
    Investigational medicinal product code
    Other name
    Diovan
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    40 mg

    Investigational medicinal product name
    Valsartan
    Investigational medicinal product code
    Other name
    Diovan
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    80 mg

    Investigational medicinal product name
    Valsartan
    Investigational medicinal product code
    Other name
    Diovan
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    160 mg

    Investigational medicinal product name
    Valsartan
    Investigational medicinal product code
    Other name
    Diovan
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to match 40 mg, 80 mg, 160 mg

    Number of subjects in period 1
    		LCZ696 Valsartan
    Started
    2419
    2403
    Completed
    2055
    2030
    Not completed
    364
    373
         Adverse event, serious fatal
    347
    356
         Consent withdrawn by subject
    4
    3
         Lost to follow-up
    13
    14

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    LCZ696
    Reporting group description
    		 Single Blind Run-in Period (3-8 weeks): Prior optional valsartan run-in 40 mg bid for 1-2 weeks for some patients. followed by Valsartan 80 mg bid for 1-2 weeks followed by LCZ696 100 mg bid for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients could only be randomized from the run-in period if they met all of the run-in safety criteria. Target dose of LCZ696 during the double blind period was 200 mg bid

    Reporting group title
    Valsartan
    Reporting group description
    		 Single Blind Run-in Period (3-8 weeks): Prior optional valsartan run-in 40 mg bid for 1-2 weeks for some patients, followed by Valsartan 80 mg bid. for 1-2 weeks followed by LCZ696 100 mg bid for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients could only be randomized from the run-in period if they met all of the run-in safety criteria. Target dose of Valsartan during the double blind period was 160 mg bid

    Reporting group values
    		 LCZ696 Valsartan Total
    Number of subjects
    		 2419 2403 4822
    Age Categorical
    Units:
        <=18 years
    		 0 0 0
        Between 18 and 65 years
    		 415 415 830
        >=65 years
    		 2004 1988 3992
    Sex: Female, Male
    Units: Participants
        Female
    		 1247 1244 2491
        Male
    		 1172 1159 2331
    Race/Ethnicity, Customized
    Units: Subjects
        Caucasian
    		 1975 1958 3933
        Black
    		 52 50 102
        Asian
    		 297 310 607
        Native American
    		 28 23 51
        Pacific Islander
    		 0 1 1
        Other
    		 67 61 128

    End points

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    End points reporting groups
    Reporting group title
    LCZ696
    Reporting group description
    		 Single Blind Run-in Period (3-8 weeks): Prior optional valsartan run-in 40 mg bid for 1-2 weeks for some patients. followed by Valsartan 80 mg bid for 1-2 weeks followed by LCZ696 100 mg bid for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients could only be randomized from the run-in period if they met all of the run-in safety criteria. Target dose of LCZ696 during the double blind period was 200 mg bid

    Reporting group title
    Valsartan
    Reporting group description
    		 Single Blind Run-in Period (3-8 weeks): Prior optional valsartan run-in 40 mg bid for 1-2 weeks for some patients, followed by Valsartan 80 mg bid. for 1-2 weeks followed by LCZ696 100 mg bid for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients could only be randomized from the run-in period if they met all of the run-in safety criteria. Target dose of Valsartan during the double blind period was 160 mg bid

    Primary: Cumulative number of primary composite events of cardiovascular (CV) death and total (first and recurrent) HF hospitalizations.

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    End point title
    		 Cumulative number of primary composite events of cardiovascular (CV) death and total (first and recurrent) HF hospitalizations.
    End point description
    The primary objective of this study is to compare LCZ696 to valsartan in reducing the rate of the composite endpoint of CV death and total (first and recurrent) HF hospitalizations, in HF patients (New York Heart Association [NYHA] Class II-IV) with preserved ejection fraction (left ventricular ejection fraction [LVEF] ≥45%). The treatment arm with the lower rate of events will be deemed as having a successful response.
    End point type
    Primary
    End point timeframe
    Total follow up time (up to 57 months)
    End point values
    		 LCZ696 Valsartan
    Number of subjects analysed
    2407
    2389
    Units: Number of Events
        Primary Composite Events
    894
    1009
        Total Hospitalizations for heart failure
    690
    797
        Cardiovascular death
    204
    212
    Statistical analysis title
    		 Primary Composite Events
    Statistical analysis description
    Primary Composite Events
    Comparison groups
    LCZ696 v Valsartan
    Number of subjects included in analysis
    4796
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0587 [1]
    Method
    		 Proportional Rates Model (LWYY)
    Parameter type
    		 Rate Ratio
    Point estimate
    0.8698
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7526
         upper limit
    		 1.0052
    Notes
    [1] - 1-sided p-value 0.0294
    Statistical analysis title
    		 Total Hospitalizations for heart failure
    Statistical analysis description
    Total Hospitalizations for heart failure
    Comparison groups
    LCZ696 v Valsartan
    Number of subjects included in analysis
    4796
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0556 [2]
    Method
    		 Joint Frality Model
    Parameter type
    		 Rate Ratio
    Point estimate
    0.8511
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7216
         upper limit
    		 1.0039
    Notes
    [2] - 1-sided p-value 0.0278
    Statistical analysis title
    		 Cardiovascular Death
    Statistical analysis description
    Cardiovascular Death
    Comparison groups
    LCZ696 v Valsartan
    Number of subjects included in analysis
    4796
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6241 [3]
    Method
    		 Cox's proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.9531
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7863
         upper limit
    		 1.1551
    Notes
    [3] - 1-sided p-value 0.3120

    Secondary: Change in the clinical summary score from baseline to Month 8 by Kansas City Cardiomyopathy Questionnaire (KCCQ)

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    End point title
    		 Change in the clinical summary score from baseline to Month 8 by Kansas City Cardiomyopathy Questionnaire (KCCQ)
    End point description
    The KCCQ is a validated instrument for self-assessment of quality of life and health status in heart failure (HF) patients. The clinical summary score, which is derived from the physical limitations and heart failure (HF) symptoms domains of the KCCQ is a valid measure for assessing the patient’s health aspects that may be influenced by CV medications.Evaluation of change from baseline to month 8 in KCCQ a most sensitive, specific, and responsive health-related quality of life measure for heart failure symptoms and physical limitations.
    End point type
    Secondary
    End point timeframe
    Baseline, 8 months
    End point values
    		 LCZ696 Valsartan
    Number of subjects analysed
    2407
    2389
    Units: Points on a scale
        least squares mean (standard error)
    -1.5073 ( 0.3709 )
    -2.5338 ( 0.3729 )
    Statistical analysis title
    		 Clinical Summary Score
    Statistical analysis description
    Clinical Summary Score
    Comparison groups
    LCZ696 v Valsartan
    Number of subjects included in analysis
    4796
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.051
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean of Difference
    Point estimate
    1.0264
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0047
         upper limit
    		 2.0576

    Secondary: Change from baseline to Month 8 in New York Heart Association (NYHA) functional class

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    End point title
    		 Change from baseline to Month 8 in New York Heart Association (NYHA) functional class
    End point description
    Evaluation of change from baseline to Month 8 in NYHA functional class, a well established grading scale used to classify a heart failure's (HF) patients' level of functionality based on the signs and symptoms of HF exhibited by the patient.
    End point type
    Secondary
    End point timeframe
    Baseline, 8 months
    End point values
    		 LCZ696 Valsartan
    Number of subjects analysed
    2407
    2389
    Units: Number of Participants
        Improved (n=2316, 2302)
    347
    289
        Unchanged (n=2316, 2302)
    1767
    1792
        Worsened (n=2316, 2302)
    202
    221
    Statistical analysis title
    		 NYHA Class Change
    Statistical analysis description
    NYHA Class Change
    Comparison groups
    LCZ696 v Valsartan
    Number of subjects included in analysis
    4796
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0035
    Method
    		 Repeated measures cumulative odds model
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.4475
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.1294
         upper limit
    		 1.8552

    Secondary: Time to first occurance of a composite renal endpoint

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    End point title
    		 Time to first occurance of a composite renal endpoint
    End point description
    Analyis of composite renal endpoint defined as renal death, or reaching ESRD, or ≥50% decline in eGFR relative to baseline, using Cox's proportional hazards model.
    End point type
    Secondary
    End point timeframe
    Randomization to total follow-up time (up to 57 months)
    End point values
    		 LCZ696 Valsartan
    Number of subjects analysed
    2407
    2389
    Units: Participants with first event
        Composite renal endpoint
    33
    64
        Renal Death
    1
    1
        Reaching ESRD
    7
    12
        >=50% decline in eGFR from baseline
    27
    60
    Statistical analysis title
    		 Composite renal endpoint
    Statistical analysis description
    Composite renal endpoint
    Comparison groups
    LCZ696 v Valsartan
    Number of subjects included in analysis
    4796
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0014
    Method
    		 Cox's proportional hazards model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.5041
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3312
         upper limit
    		 0.7673
    Statistical analysis title
    		 Renal Death
    Statistical analysis description
    Renal Death
    Comparison groups
    LCZ696 v Valsartan
    Number of subjects included in analysis
    4796
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9588
    Method
    		 Cox's proportional hazards model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.9295
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.0581
         upper limit
    		 14.861
    Statistical analysis title
    		 Reaching ESRD
    Statistical analysis description
    Reaching ESRD
    Comparison groups
    LCZ696 v Valsartan
    Number of subjects included in analysis
    4796
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2484
    Method
    		 Cox's proportional hazards model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.5774
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2272
         upper limit
    		 1.4672
    Statistical analysis title
    		 >=50% decline in eGFR from baseline
    Statistical analysis description
    >=50% decline in eGFR from baseline
    Comparison groups
    LCZ696 v Valsartan
    Number of subjects included in analysis
    4796
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0004
    Method
    		 Cox's proportional hazards model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.4407
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2798
         upper limit
    		 0.6942

    Secondary: Time to all-cause mortality

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    End point title
    		 Time to all-cause mortality
    End point description
    Analysis for all-cause mortality using Cox's proportional hazards model.
    End point type
    Secondary
    End point timeframe
    Randomization to total follow up time (up to 57 months)
    End point values
    		 LCZ696 Valsartan
    Number of subjects analysed
    2407
    2389
    Units: Participants with 1st event
    342
    349
    Statistical analysis title
    		 All-cause mortality
    Statistical analysis description
    All-cause mortality
    Comparison groups
    LCZ696 v Valsartan
    Number of subjects included in analysis
    4796
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6846
    Method
    		 Cox's proportional hazards model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.9696
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8352
         upper limit
    		 1.1255

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of approx. 5 years.
    Adverse event reporting additional description
    Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. Safety set included all randomized patients minus 1 patient who did not receive study drug: 4821 patients.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Valsartan
    Reporting group description
    		 Valsartan

    Reporting group title
    LCZ696
    Reporting group description
    		 LCZ696

    Reporting group title
    All patients
    Reporting group description
    		 All patients

    Serious adverse events
    		 Valsartan LCZ696 All patients
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1416 / 2402 (58.95%)
    1424 / 2419 (58.87%)
    2840 / 4821 (58.91%)
         number of deaths (all causes)
    357
    347
    704
         number of deaths resulting from adverse events
    5
    5
    10
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Acute myeloid leukaemia
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute promyelocytic leukaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Adenocarcinoma
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    Adenocarcinoma gastric
         subjects affected / exposed
    1 / 2402 (0.04%)
    3 / 2419 (0.12%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Adenocarcinoma of colon
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal cancer stage 0
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    11 / 2402 (0.46%)
    11 / 2419 (0.45%)
    22 / 4821 (0.46%)
         occurrences causally related to treatment / all
    0 / 12
    1 / 14
    1 / 26
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Benign gastrointestinal neoplasm
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Benign lung neoplasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Benign pancreatic neoplasm
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Bile duct cancer
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    Bladder cancer
         subjects affected / exposed
    5 / 2402 (0.21%)
    2 / 2419 (0.08%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Bladder neoplasm
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone cancer
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Bowen's disease
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Brain neoplasm malignant
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Breast angiosarcoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Breast cancer
         subjects affected / exposed
    8 / 2402 (0.33%)
    6 / 2419 (0.25%)
    14 / 4821 (0.29%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 6
    0 / 15
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Breast neoplasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    4 / 2419 (0.17%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Carcinoma in situ of skin
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Central nervous system lymphoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic myeloid leukaemia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colon adenoma
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    4 / 2402 (0.17%)
    5 / 2419 (0.21%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 5
    1 / 9
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Colon cancer metastatic
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Colon neoplasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Colorectal cancer
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Diffuse large B-cell lymphoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Endometrial adenocarcinoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endometrial cancer
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Fibroma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gallbladder cancer
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Gallbladder neoplasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
    Gastric neoplasm
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal neoplasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stromal tumour
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Gastrointestinal tract adenoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glioblastoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemangioma of liver
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic cancer
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    Hepatic cancer metastatic
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hepatic neoplasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hepatocellular carcinoma
         subjects affected / exposed
    2 / 2402 (0.08%)
    5 / 2419 (0.21%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    Hormone-refractory prostate cancer
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal adenocarcinoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Invasive breast carcinoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Invasive lobular breast carcinoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Invasive papillary breast carcinoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Kaposi's sarcoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal squamous cell carcinoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leiomyoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lip and/or oral cavity cancer
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lip squamous cell carcinoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lipoma
         subjects affected / exposed
    2 / 2402 (0.08%)
    3 / 2419 (0.12%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Lung carcinoma cell type unspecified stage II
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Lung neoplasm malignant
         subjects affected / exposed
    10 / 2402 (0.42%)
    8 / 2419 (0.33%)
    18 / 4821 (0.37%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 8
    0 / 18
         deaths causally related to treatment / all
    0 / 3
    0 / 4
    0 / 7
    Lymphoma
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphoproliferative disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant mediastinal neoplasm
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Malignant melanoma
         subjects affected / exposed
    6 / 2402 (0.25%)
    7 / 2419 (0.29%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 7
    1 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Malignant neoplasm of unknown primary site
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Malignant pleural effusion
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Mantle cell lymphoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mediastinum neoplasm
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Meningioma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mesothelioma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Metastases to bone
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Metastases to central nervous system
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Metastases to liver
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Metastases to lung
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Metastases to lymph nodes
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Metastasis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Metastatic carcinoma of the bladder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastatic lymphoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Metastatic malignant melanoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Metastatic squamous cell carcinoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Monoclonal gammopathy
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Myeloid leukaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Myeloproliferative neoplasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Neoplasm skin
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Oesophageal adenocarcinoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oncologic complication
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Oral haemangioma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal cancer
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Oropharyngeal squamous cell carcinoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Ovarian cancer
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Ovarian epithelial cancer
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    2 / 2402 (0.08%)
    4 / 2419 (0.17%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
    Pancreatic neoplasm
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Papilloma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Penile cancer
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Prostate cancer
         subjects affected / exposed
    8 / 2402 (0.33%)
    7 / 2419 (0.29%)
    15 / 4821 (0.31%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 7
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer metastatic
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatic adenoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    3 / 2402 (0.12%)
    2 / 2419 (0.08%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    4 / 2402 (0.17%)
    6 / 2419 (0.25%)
    10 / 4821 (0.21%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Rectal cancer metastatic
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Rectal cancer recurrent
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal neoplasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal neoplasm
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sarcoma uterus
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Schwannoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seborrhoeic keratosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin cancer
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin neoplasm bleeding
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Squamous cell carcinoma
         subjects affected / exposed
    8 / 2402 (0.33%)
    6 / 2419 (0.25%)
    14 / 4821 (0.29%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 7
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    1 / 2402 (0.04%)
    4 / 2419 (0.17%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Transitional cell carcinoma
         subjects affected / exposed
    4 / 2402 (0.17%)
    0 / 2419 (0.00%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma recurrent
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour compression
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour embolism
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Ureteral neoplasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureteric cancer
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine cancer
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal adenocarcinoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal cancer
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Waldenstrom's macroglobulinaemia
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Accelerated hypertension
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angiopathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    8 / 2402 (0.33%)
    2 / 2419 (0.08%)
    10 / 4821 (0.21%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic aneurysm rupture
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    Aortic dissection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic rupture
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    12 / 2402 (0.50%)
    13 / 2419 (0.54%)
    25 / 4821 (0.52%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 13
    0 / 25
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Aortic thrombosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arterial occlusive disease
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bleeding varicose vein
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood pressure fluctuation
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    2 / 2402 (0.08%)
    3 / 2419 (0.12%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    7 / 2402 (0.29%)
    4 / 2419 (0.17%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 4
    1 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dry gangrene
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Essential hypertension
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    8 / 2402 (0.33%)
    7 / 2419 (0.29%)
    15 / 4821 (0.31%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 7
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic infarction
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    25 / 2402 (1.04%)
    16 / 2419 (0.66%)
    41 / 4821 (0.85%)
         occurrences causally related to treatment / all
    0 / 30
    0 / 16
    0 / 46
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    8 / 2402 (0.33%)
    4 / 2419 (0.17%)
    12 / 4821 (0.25%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 6
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Hypertensive urgency
         subjects affected / exposed
    1 / 2402 (0.04%)
    6 / 2419 (0.25%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    47 / 2402 (1.96%)
    52 / 2419 (2.15%)
    99 / 4821 (2.05%)
         occurrences causally related to treatment / all
    22 / 52
    24 / 60
    46 / 112
         deaths causally related to treatment / all
    0 / 1
    1 / 3
    1 / 4
    Hypovolaemic shock
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Iliac artery embolism
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leriche syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphoedema
         subjects affected / exposed
    4 / 2402 (0.17%)
    0 / 2419 (0.00%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Orthostatic hypertension
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    9 / 2402 (0.37%)
    5 / 2419 (0.21%)
    14 / 4821 (0.29%)
         occurrences causally related to treatment / all
    3 / 9
    1 / 5
    4 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    7 / 2402 (0.29%)
    18 / 2419 (0.74%)
    25 / 4821 (0.52%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 19
    0 / 28
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral coldness
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral embolism
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 3
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    7 / 2402 (0.29%)
    8 / 2419 (0.33%)
    15 / 4821 (0.31%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Peripheral vascular disorder
         subjects affected / exposed
    2 / 2402 (0.08%)
    5 / 2419 (0.21%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral venous disease
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post thrombotic syndrome
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    5 / 2402 (0.21%)
    2 / 2419 (0.08%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Subclavian artery stenosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subclavian artery thrombosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Temporal arteritis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Varicose ulceration
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    21 / 2402 (0.87%)
    12 / 2419 (0.50%)
    33 / 4821 (0.68%)
         occurrences causally related to treatment / all
    3 / 23
    0 / 12
    3 / 35
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cardiac death
         subjects affected / exposed
    6 / 2402 (0.25%)
    3 / 2419 (0.12%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 3
    1 / 9
         deaths causally related to treatment / all
    1 / 6
    0 / 3
    1 / 9
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    1 / 2402 (0.04%)
    4 / 2419 (0.17%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Concomitant disease progression
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Condition aggravated
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    23 / 2402 (0.96%)
    34 / 2419 (1.41%)
    57 / 4821 (1.18%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 34
    0 / 57
         deaths causally related to treatment / all
    0 / 23
    0 / 34
    0 / 57
    Disuse syndrome
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Euthanasia
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Fatigue
         subjects affected / exposed
    4 / 2402 (0.17%)
    4 / 2419 (0.17%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 8
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    5 / 2402 (0.21%)
    9 / 2419 (0.37%)
    14 / 4821 (0.29%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 9
    1 / 15
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
    Hyperthermia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ill-defined disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 2402 (0.00%)
    3 / 2419 (0.12%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impaired self-care
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Implant site haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated hernia
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lithiasis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mass
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Medical device discomfort
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    7 / 2402 (0.29%)
    10 / 2419 (0.41%)
    17 / 4821 (0.35%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 10
    0 / 17
         deaths causally related to treatment / all
    0 / 7
    0 / 9
    0 / 16
    Necrosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    37 / 2402 (1.54%)
    42 / 2419 (1.74%)
    79 / 4821 (1.64%)
         occurrences causally related to treatment / all
    0 / 51
    0 / 51
    0 / 102
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    12 / 2402 (0.50%)
    6 / 2419 (0.25%)
    18 / 4821 (0.37%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 6
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Peripheral swelling
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    13 / 2402 (0.54%)
    8 / 2419 (0.33%)
    21 / 4821 (0.44%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 10
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Stenosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    16 / 2402 (0.67%)
    15 / 2419 (0.62%)
    31 / 4821 (0.64%)
         occurrences causally related to treatment / all
    1 / 16
    0 / 15
    1 / 31
         deaths causally related to treatment / all
    1 / 16
    0 / 15
    1 / 31
    Sudden death
         subjects affected / exposed
    22 / 2402 (0.92%)
    21 / 2419 (0.87%)
    43 / 4821 (0.89%)
         occurrences causally related to treatment / all
    1 / 22
    0 / 21
    1 / 43
         deaths causally related to treatment / all
    1 / 22
    0 / 21
    1 / 43
    Surgical failure
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Swelling
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    5 / 2402 (0.21%)
    1 / 2419 (0.04%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Treatment noncompliance
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulcer haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Unevaluable event
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular stent stenosis
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Food allergy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sarcoidosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    Immobile
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Living in residential institution
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Adenomyosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Benign prostatic hyperplasia
         subjects affected / exposed
    5 / 2402 (0.21%)
    8 / 2419 (0.33%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 8
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast calcifications
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast cyst
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast mass
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervical dysplasia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervical polyp
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endometrial thickening
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erectile dysfunction
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metrorrhagia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postmenopausal haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatic haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatic obstruction
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Scrotal inflammation
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spermatocele
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    14 / 2402 (0.58%)
    12 / 2419 (0.50%)
    26 / 4821 (0.54%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 13
    0 / 28
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    24 / 2402 (1.00%)
    20 / 2419 (0.83%)
    44 / 4821 (0.91%)
         occurrences causally related to treatment / all
    0 / 28
    0 / 22
    0 / 50
         deaths causally related to treatment / all
    0 / 9
    0 / 7
    0 / 16
    Aspiration
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Asthma
         subjects affected / exposed
    10 / 2402 (0.42%)
    9 / 2419 (0.37%)
    19 / 4821 (0.39%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 10
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Bronchial obstruction
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Bronchitis chronic
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    67 / 2402 (2.79%)
    42 / 2419 (1.74%)
    109 / 4821 (2.26%)
         occurrences causally related to treatment / all
    1 / 92
    0 / 65
    1 / 157
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    0 / 5
    Chronic respiratory failure
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Cough
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Dyspnoea
         subjects affected / exposed
    64 / 2402 (2.66%)
    42 / 2419 (1.74%)
    106 / 4821 (2.20%)
         occurrences causally related to treatment / all
    2 / 75
    0 / 50
    2 / 125
         deaths causally related to treatment / all
    0 / 6
    0 / 1
    0 / 7
    Dyspnoea at rest
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    5 / 2402 (0.21%)
    4 / 2419 (0.17%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    4 / 2402 (0.17%)
    4 / 2419 (0.17%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    5 / 2402 (0.21%)
    2 / 2419 (0.08%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Haemothorax
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydrothorax
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercapnia
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Hypoventilation
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    6 / 2402 (0.25%)
    2 / 2419 (0.08%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Interstitial lung disease
         subjects affected / exposed
    3 / 2402 (0.12%)
    4 / 2419 (0.17%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Laryngeal haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal oedema
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngospasm
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mediastinal mass
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nasal septum deviation
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obstructive airways disorder
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthopnoea
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngeal haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pickwickian syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    15 / 2402 (0.62%)
    17 / 2419 (0.70%)
    32 / 4821 (0.66%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 23
    0 / 40
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Pleurisy
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Pneumonia aspiration
         subjects affected / exposed
    11 / 2402 (0.46%)
    7 / 2419 (0.29%)
    18 / 4821 (0.37%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 8
    0 / 19
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
    Pneumonitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 2402 (0.04%)
    4 / 2419 (0.17%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presbyphonia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary alveolar haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary arterial hypertension
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    5 / 2402 (0.21%)
    0 / 2419 (0.00%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    17 / 2402 (0.71%)
    16 / 2419 (0.66%)
    33 / 4821 (0.68%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 17
    0 / 34
         deaths causally related to treatment / all
    0 / 4
    0 / 4
    0 / 8
    Pulmonary eosinophilia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    3 / 2419 (0.12%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Pulmonary hypertension
         subjects affected / exposed
    9 / 2402 (0.37%)
    4 / 2419 (0.17%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 5
    0 / 15
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Pulmonary mass
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    16 / 2402 (0.67%)
    7 / 2419 (0.29%)
    23 / 4821 (0.48%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 7
    0 / 24
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Respiratory acidosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Respiratory depression
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Respiratory failure
         subjects affected / exposed
    32 / 2402 (1.33%)
    29 / 2419 (1.20%)
    61 / 4821 (1.27%)
         occurrences causally related to treatment / all
    0 / 39
    0 / 32
    0 / 71
         deaths causally related to treatment / all
    0 / 13
    0 / 13
    0 / 26
    Respiratory tract congestion
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    5 / 2402 (0.21%)
    4 / 2419 (0.17%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Status asthmaticus
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tracheal stenosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vocal cord polyp
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wheezing
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Acute stress disorder
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adjustment disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adjustment disorder with mixed anxiety and depressed mood
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Agitation
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Alcoholism
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Anxiety disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Behaviour disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    2 / 2402 (0.08%)
    4 / 2419 (0.17%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 4
    0 / 6
    Confusional state
         subjects affected / exposed
    7 / 2402 (0.29%)
    6 / 2419 (0.25%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    1 / 7
    2 / 8
    3 / 15
         deaths causally related to treatment / all
    0 / 1
    1 / 1
    1 / 2
    Delirium
         subjects affected / exposed
    11 / 2402 (0.46%)
    7 / 2419 (0.29%)
    18 / 4821 (0.37%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 8
    0 / 19
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Delirium febrile
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Delusion
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depressed mood
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Depression
         subjects affected / exposed
    7 / 2402 (0.29%)
    6 / 2419 (0.25%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 7
    1 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Hallucination
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental disorder due to a general medical condition
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    5 / 2402 (0.21%)
    3 / 2419 (0.12%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 3
    1 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Organic brain syndrome
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paranoia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Personality disorder
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Somatic symptom disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device battery issue
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device breakage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device damage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device defective
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 3
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device failure
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device leakage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device loosening
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device occlusion
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lead dislodgement
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bile duct stenosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    4 / 2402 (0.17%)
    5 / 2419 (0.21%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary dyskinesia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    4 / 2402 (0.17%)
    4 / 2419 (0.17%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cholecystitis
         subjects affected / exposed
    11 / 2402 (0.46%)
    14 / 2419 (0.58%)
    25 / 4821 (0.52%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 15
    1 / 26
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    9 / 2402 (0.37%)
    8 / 2419 (0.33%)
    17 / 4821 (0.35%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 8
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Cholecystitis chronic
         subjects affected / exposed
    2 / 2402 (0.08%)
    5 / 2419 (0.21%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    19 / 2402 (0.79%)
    17 / 2419 (0.70%)
    36 / 4821 (0.75%)
         occurrences causally related to treatment / all
    2 / 19
    0 / 19
    2 / 38
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cholelithiasis migration
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic hepatic failure
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cirrhosis alcoholic
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cryptogenic cirrhosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gallbladder disorder
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Gallbladder rupture
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemobilia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    6 / 2402 (0.25%)
    4 / 2419 (0.17%)
    10 / 4821 (0.21%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 4
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Hepatic cyst
         subjects affected / exposed
    6 / 2402 (0.25%)
    5 / 2419 (0.21%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    Hepatic function abnormal
         subjects affected / exposed
    5 / 2402 (0.21%)
    5 / 2419 (0.21%)
    10 / 4821 (0.21%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Hepatic lesion
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic mass
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic steatosis
         subjects affected / exposed
    10 / 2402 (0.42%)
    10 / 2419 (0.41%)
    20 / 4821 (0.41%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 10
    0 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disease
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatomegaly
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hepatorenal syndrome
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Hepatosplenomegaly
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    5 / 2402 (0.21%)
    8 / 2419 (0.33%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 8
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Liver disorder
         subjects affected / exposed
    4 / 2402 (0.17%)
    1 / 2419 (0.04%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nonalcoholic fatty liver disease
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Portal hypertension
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Portal vein thrombosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Primary biliary cholangitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Steatohepatitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anticoagulation drug level above therapeutic
         subjects affected / exposed
    4 / 2402 (0.17%)
    2 / 2419 (0.08%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 2402 (0.08%)
    4 / 2419 (0.17%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 4
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bleeding time abnormal
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    4 / 2402 (0.17%)
    1 / 2419 (0.04%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 1
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood glucose abnormal
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood glucose decreased
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood glucose fluctuation
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood glucose increased
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood osmolarity decreased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood pressure decreased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood sodium decreased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain natriuretic peptide increased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac output decreased
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coagulation time prolonged
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram repolarisation abnormality
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical condition abnormal
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glomerular filtration rate decreased
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Heart rate decreased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Heart rate irregular
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    6 / 2402 (0.25%)
    7 / 2419 (0.29%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 7
    1 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inflammatory marker increased
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Influenza virus test positive
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    2 / 2402 (0.08%)
    3 / 2419 (0.12%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Lipase increased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial necrosis marker increased
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Precancerous cells present
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatic specific antigen increased
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulse absent
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory rate increased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Troponin I increased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Troponin T increased
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    4 / 2402 (0.17%)
    0 / 2419 (0.00%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urine output decreased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventilation/perfusion scan abnormal
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Visual field tests abnormal
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Abdominal injury
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Accident
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Accidental overdose
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acetabulum fracture
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia postoperative
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anastomotic leak
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anastomotic ulcer
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Animal bite
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    4 / 2402 (0.17%)
    7 / 2419 (0.29%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arterial bypass occlusion
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Avulsion fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone contusion
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain herniation
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Carbon monoxide poisoning
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac function disturbance postoperative
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest injury
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Comminuted fracture
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Complications of transplanted kidney
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    3 / 2402 (0.12%)
    4 / 2419 (0.17%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary bypass stenosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Cystitis radiation
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Extra dose administered
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Extradural haematoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye injury
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    26 / 2402 (1.08%)
    33 / 2419 (1.36%)
    59 / 4821 (1.22%)
         occurrences causally related to treatment / all
    2 / 29
    3 / 37
    5 / 66
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    Femoral neck fracture
         subjects affected / exposed
    8 / 2402 (0.33%)
    5 / 2419 (0.21%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Femur fracture
         subjects affected / exposed
    20 / 2402 (0.83%)
    11 / 2419 (0.45%)
    31 / 4821 (0.64%)
         occurrences causally related to treatment / all
    0 / 21
    0 / 11
    0 / 32
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Foot fracture
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fractured coccyx
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stoma complication
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    6 / 2402 (0.25%)
    5 / 2419 (0.21%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hip fracture
         subjects affected / exposed
    14 / 2402 (0.58%)
    13 / 2419 (0.54%)
    27 / 4821 (0.56%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 14
    0 / 28
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Humerus fracture
         subjects affected / exposed
    7 / 2402 (0.29%)
    5 / 2419 (0.21%)
    12 / 4821 (0.25%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypobarism
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incision site haematoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Joint dislocation
         subjects affected / exposed
    3 / 2402 (0.12%)
    2 / 2419 (0.08%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ligament injury
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Limb crushing injury
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    1 / 2402 (0.04%)
    4 / 2419 (0.17%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    2 / 2402 (0.08%)
    3 / 2419 (0.12%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Meniscus injury
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Muscle strain
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nerve root injury cervical
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Overdose
         subjects affected / exposed
    2 / 2402 (0.08%)
    4 / 2419 (0.17%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Patella fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Periprosthetic fracture
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural myocardial infarction
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post-traumatic pain
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative hypotension
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative respiratory failure
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Postoperative wound complication
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural pneumothorax
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural vomiting
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radiation proctitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    7 / 2419 (0.29%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory fume inhalation disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Rib fracture
         subjects affected / exposed
    6 / 2402 (0.25%)
    11 / 2419 (0.45%)
    17 / 4821 (0.35%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 11
    0 / 17
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Road traffic accident
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sedation complication
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Skin abrasion
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    2 / 2402 (0.08%)
    6 / 2419 (0.25%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    8 / 2402 (0.33%)
    3 / 2419 (0.12%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    2 / 2402 (0.08%)
    6 / 2419 (0.25%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Splenic rupture
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomal hernia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    8 / 2402 (0.33%)
    7 / 2419 (0.29%)
    15 / 4821 (0.31%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 10
    1 / 18
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
    Subdural haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    8 / 2402 (0.33%)
    2 / 2419 (0.08%)
    10 / 4821 (0.21%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic haematoma
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic liver injury
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Vascular graft occlusion
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular pseudoaneurysm ruptured
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound complication
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital coronary artery malformation
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital megaureter
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal arteriovenous malformation
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUMBAR syndrome
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Phimosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertebral artery hypoplasia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    13 / 2402 (0.54%)
    11 / 2419 (0.45%)
    24 / 4821 (0.50%)
         occurrences causally related to treatment / all
    0 / 15
    1 / 11
    1 / 26
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Acute left ventricular failure
         subjects affected / exposed
    15 / 2402 (0.62%)
    14 / 2419 (0.58%)
    29 / 4821 (0.60%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 22
    0 / 41
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    Acute myocardial infarction
         subjects affected / exposed
    54 / 2402 (2.25%)
    60 / 2419 (2.48%)
    114 / 4821 (2.36%)
         occurrences causally related to treatment / all
    0 / 61
    0 / 69
    0 / 130
         deaths causally related to treatment / all
    0 / 9
    0 / 8
    0 / 17
    Adams-Stokes syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    50 / 2402 (2.08%)
    42 / 2419 (1.74%)
    92 / 4821 (1.91%)
         occurrences causally related to treatment / all
    1 / 57
    1 / 49
    2 / 106
         deaths causally related to treatment / all
    0 / 0
    0 / 4
    0 / 4
    Angina unstable
         subjects affected / exposed
    43 / 2402 (1.79%)
    50 / 2419 (2.07%)
    93 / 4821 (1.93%)
         occurrences causally related to treatment / all
    0 / 52
    0 / 61
    0 / 113
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Aortic valve stenosis
         subjects affected / exposed
    3 / 2402 (0.12%)
    4 / 2419 (0.17%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    4 / 2402 (0.17%)
    4 / 2419 (0.17%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 4
    1 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Arrhythmia supraventricular
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    4 / 2402 (0.17%)
    4 / 2419 (0.17%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    145 / 2402 (6.04%)
    162 / 2419 (6.70%)
    307 / 4821 (6.37%)
         occurrences causally related to treatment / all
    4 / 196
    8 / 220
    12 / 416
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Atrial flutter
         subjects affected / exposed
    23 / 2402 (0.96%)
    31 / 2419 (1.28%)
    54 / 4821 (1.12%)
         occurrences causally related to treatment / all
    1 / 27
    2 / 38
    3 / 65
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Atrial tachycardia
         subjects affected / exposed
    2 / 2402 (0.08%)
    7 / 2419 (0.29%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 9
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    4 / 2402 (0.17%)
    6 / 2419 (0.25%)
    10 / 4821 (0.21%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    11 / 2402 (0.46%)
    8 / 2419 (0.33%)
    19 / 4821 (0.39%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 8
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    3 / 2402 (0.12%)
    4 / 2419 (0.17%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradyarrhythmia
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Bradycardia
         subjects affected / exposed
    24 / 2402 (1.00%)
    27 / 2419 (1.12%)
    51 / 4821 (1.06%)
         occurrences causally related to treatment / all
    1 / 26
    0 / 27
    1 / 53
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Bundle branch block left
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac amyloidosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Cardiac arrest
         subjects affected / exposed
    30 / 2402 (1.25%)
    17 / 2419 (0.70%)
    47 / 4821 (0.97%)
         occurrences causally related to treatment / all
    0 / 30
    1 / 17
    1 / 47
         deaths causally related to treatment / all
    0 / 21
    1 / 13
    1 / 34
    Cardiac asthma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Cardiac discomfort
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    380 / 2402 (15.82%)
    340 / 2419 (14.06%)
    720 / 4821 (14.93%)
         occurrences causally related to treatment / all
    15 / 652
    5 / 529
    20 / 1181
         deaths causally related to treatment / all
    1 / 49
    0 / 41
    1 / 90
    Cardiac failure acute
         subjects affected / exposed
    77 / 2402 (3.21%)
    85 / 2419 (3.51%)
    162 / 4821 (3.36%)
         occurrences causally related to treatment / all
    1 / 109
    1 / 113
    2 / 222
         deaths causally related to treatment / all
    0 / 7
    0 / 10
    0 / 17
    Cardiac failure chronic
         subjects affected / exposed
    30 / 2402 (1.25%)
    26 / 2419 (1.07%)
    56 / 4821 (1.16%)
         occurrences causally related to treatment / all
    1 / 47
    4 / 38
    5 / 85
         deaths causally related to treatment / all
    0 / 4
    1 / 5
    1 / 9
    Cardiac failure congestive
         subjects affected / exposed
    83 / 2402 (3.46%)
    86 / 2419 (3.56%)
    169 / 4821 (3.51%)
         occurrences causally related to treatment / all
    0 / 155
    5 / 146
    5 / 301
         deaths causally related to treatment / all
    0 / 5
    0 / 13
    0 / 18
    Cardiac fibrillation
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac flutter
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac ventricular disorder
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    13 / 2402 (0.54%)
    15 / 2419 (0.62%)
    28 / 4821 (0.58%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 15
    0 / 28
         deaths causally related to treatment / all
    0 / 11
    0 / 12
    0 / 23
    Cardiogenic shock
         subjects affected / exposed
    6 / 2402 (0.25%)
    12 / 2419 (0.50%)
    18 / 4821 (0.37%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 12
    1 / 18
         deaths causally related to treatment / all
    0 / 4
    0 / 6
    0 / 10
    Cardiomegaly
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 2402 (0.04%)
    4 / 2419 (0.17%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    0 / 5
    Cardiorenal syndrome
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiovascular disorder
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Cardiovascular insufficiency
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    Chronic left ventricular failure
         subjects affected / exposed
    1 / 2402 (0.04%)
    3 / 2419 (0.12%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    27 / 2402 (1.12%)
    24 / 2419 (0.99%)
    51 / 4821 (1.06%)
         occurrences causally related to treatment / all
    0 / 30
    1 / 25
    1 / 55
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Coronary artery occlusion
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    2 / 2402 (0.08%)
    5 / 2419 (0.21%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive heart disease
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Intracardiac mass
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    4 / 2419 (0.17%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    5 / 2402 (0.21%)
    6 / 2419 (0.25%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Microvascular coronary artery disease
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mitral valve calcification
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    8 / 2402 (0.33%)
    7 / 2419 (0.29%)
    15 / 4821 (0.31%)
         occurrences causally related to treatment / all
    0 / 10
    1 / 7
    1 / 17
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Mitral valve prolapse
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    35 / 2402 (1.46%)
    32 / 2419 (1.32%)
    67 / 4821 (1.39%)
         occurrences causally related to treatment / all
    1 / 38
    1 / 36
    2 / 74
         deaths causally related to treatment / all
    1 / 13
    0 / 11
    1 / 24
    Myocardial ischaemia
         subjects affected / exposed
    11 / 2402 (0.46%)
    7 / 2419 (0.29%)
    18 / 4821 (0.37%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 7
    0 / 18
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Myocardial rupture
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Myocarditis
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Nodal rhythm
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericarditis constrictive
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulseless electrical activity
         subjects affected / exposed
    1 / 2402 (0.04%)
    3 / 2419 (0.12%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Right ventricular dysfunction
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Right ventricular failure
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinoatrial block
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus arrest
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    8 / 2402 (0.33%)
    1 / 2419 (0.04%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 1
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    12 / 2402 (0.50%)
    18 / 2419 (0.74%)
    30 / 4821 (0.62%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 30
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    3 / 2402 (0.12%)
    6 / 2419 (0.25%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 11
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systolic dysfunction
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    0 / 2402 (0.00%)
    3 / 2419 (0.12%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 2402 (0.04%)
    3 / 2419 (0.12%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Torsade de pointes
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Trifascicular block
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular dyssynchrony
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    5 / 2402 (0.21%)
    4 / 2419 (0.17%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
    0 / 10
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Ventricular tachycardia
         subjects affected / exposed
    4 / 2402 (0.17%)
    9 / 2419 (0.37%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 9
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Nervous system disorders
    Altered state of consciousness
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Amyotrophic lateral sclerosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    4 / 2402 (0.17%)
    1 / 2419 (0.04%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain hypoxia
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain injury
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Brain oedema
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Brain stem stroke
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carotid artery aneurysm
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carotid artery disease
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    7 / 2402 (0.29%)
    9 / 2419 (0.37%)
    16 / 4821 (0.33%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 10
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Central nervous system lesion
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebellar haematoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cerebellar infarction
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebellar ischaemia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral arteriosclerosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral artery embolism
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral cyst
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cerebral haemorrhage
         subjects affected / exposed
    6 / 2402 (0.25%)
    5 / 2419 (0.21%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 11
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
    Cerebral infarction
         subjects affected / exposed
    18 / 2402 (0.75%)
    17 / 2419 (0.70%)
    35 / 4821 (0.73%)
         occurrences causally related to treatment / all
    0 / 20
    1 / 20
    1 / 40
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Cerebral ischaemia
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    2 / 3
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral thrombosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrospinal fluid leakage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    42 / 2402 (1.75%)
    39 / 2419 (1.61%)
    81 / 4821 (1.68%)
         occurrences causally related to treatment / all
    0 / 48
    2 / 46
    2 / 94
         deaths causally related to treatment / all
    0 / 8
    1 / 10
    1 / 18
    Cerebrovascular disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular insufficiency
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervicobrachial syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    2 / 2402 (0.08%)
    7 / 2419 (0.29%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 7
    2 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Coma
         subjects affected / exposed
    4 / 2402 (0.17%)
    1 / 2419 (0.04%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Dementia
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Dementia Alzheimer's type
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Dementia with Lewy bodies
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidotic hyperglycaemic coma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic neuropathy
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    11 / 2402 (0.46%)
    17 / 2419 (0.70%)
    28 / 4821 (0.58%)
         occurrences causally related to treatment / all
    2 / 11
    4 / 19
    6 / 30
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    4 / 2402 (0.17%)
    5 / 2419 (0.21%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Encephalopathy
         subjects affected / exposed
    6 / 2402 (0.25%)
    1 / 2419 (0.04%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Epilepsy
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Facial paralysis
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Haemorrhagic cerebral infarction
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Haemorrhagic stroke
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Haemorrhagic transformation stroke
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    10 / 2402 (0.42%)
    3 / 2419 (0.12%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 3
    0 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hemiparesis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hemiplegia
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Hepatic encephalopathy
         subjects affected / exposed
    5 / 2402 (0.21%)
    1 / 2419 (0.04%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 1
    1 / 9
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Hydrocephalus
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 2402 (0.00%)
    3 / 2419 (0.12%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemic coma
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    IIIrd nerve paralysis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intracranial haematoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intracranial pressure increased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Ischaemic stroke
         subjects affected / exposed
    29 / 2402 (1.21%)
    32 / 2419 (1.32%)
    61 / 4821 (1.27%)
         occurrences causally related to treatment / all
    0 / 29
    0 / 36
    0 / 65
         deaths causally related to treatment / all
    0 / 5
    0 / 4
    0 / 9
    Lacunar infarction
         subjects affected / exposed
    2 / 2402 (0.08%)
    4 / 2419 (0.17%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 3
    1 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Lumbar radiculopathy
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbosacral radiculopathy
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    3 / 2402 (0.12%)
    6 / 2419 (0.25%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mixed dementia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Motor dysfunction
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Movement disorder
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple system atrophy
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myasthenic syndrome
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myelopathy
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myoclonus
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Neuralgia
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parkinsonism
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post herpetic neuralgia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post stroke epilepsy
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudoradicular syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Resting tremor
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    4 / 2402 (0.17%)
    4 / 2419 (0.17%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 2402 (0.08%)
    6 / 2419 (0.25%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sensory disturbance
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Somnolence
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Speech disorder
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spondylitic myelopathy
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stroke in evolution
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Syncope
         subjects affected / exposed
    57 / 2402 (2.37%)
    41 / 2419 (1.69%)
    98 / 4821 (2.03%)
         occurrences causally related to treatment / all
    9 / 67
    12 / 44
    21 / 111
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Thalamus haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombotic cerebral infarction
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombotic stroke
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Toxic encephalopathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    26 / 2402 (1.08%)
    34 / 2419 (1.41%)
    60 / 4821 (1.24%)
         occurrences causally related to treatment / all
    1 / 26
    2 / 37
    3 / 63
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
    Tremor
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Unresponsive to stimuli
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Uraemic encephalopathy
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VIth nerve paresis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular dementia
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular parkinsonism
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    2 / 2402 (0.08%)
    4 / 2419 (0.17%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo CNS origin
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Acquired haemophilia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    67 / 2402 (2.79%)
    68 / 2419 (2.81%)
    135 / 4821 (2.80%)
         occurrences causally related to treatment / all
    1 / 77
    1 / 83
    2 / 160
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Anaemia macrocytic
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia megaloblastic
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia vitamin B12 deficiency
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    7 / 2402 (0.29%)
    2 / 2419 (0.08%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Coagulopathy
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hypercoagulation
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypersplenism
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune thrombocytopenic purpura
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    6 / 2402 (0.25%)
    5 / 2419 (0.21%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    6 / 2402 (0.25%)
    1 / 2419 (0.04%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Leukopenia
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy mediastinal
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    3 / 2419 (0.12%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrogenic anaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Splenic infarction
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Splenitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 2402 (0.04%)
    6 / 2419 (0.25%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Thrombocytosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness unilateral
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden hearing loss
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tinnitus
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    3 / 2402 (0.12%)
    6 / 2419 (0.25%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    1 / 2402 (0.04%)
    5 / 2419 (0.21%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vestibular ischaemia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Amaurosis fugax
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blindness unilateral
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    12 / 2402 (0.50%)
    14 / 2419 (0.58%)
    26 / 4821 (0.54%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 14
    0 / 28
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cataract diabetic
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Conjunctival haemorrhage
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Entropion
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye pain
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Macular degeneration
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Macular fibrosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Maculopathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Narrow anterior chamber angle
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neovascular age-related macular degeneration
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pterygium
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal haemorrhage
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal vein occlusion
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Visual acuity reduced
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    1 / 2402 (0.04%)
    3 / 2419 (0.12%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    8 / 2402 (0.33%)
    6 / 2419 (0.25%)
    14 / 4821 (0.29%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 6
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Abdominal wall haematoma
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal incontinence
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendiceal mucocoele
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    9 / 2402 (0.37%)
    8 / 2419 (0.33%)
    17 / 4821 (0.35%)
         occurrences causally related to treatment / all
    1 / 12
    0 / 13
    1 / 25
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Chronic gastritis
         subjects affected / exposed
    3 / 2402 (0.12%)
    2 / 2419 (0.08%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    3 / 2402 (0.12%)
    5 / 2419 (0.21%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Colitis microscopic
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 2402 (0.00%)
    3 / 2419 (0.12%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    6 / 2402 (0.25%)
    2 / 2419 (0.08%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic gastroenteropathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diaphragmatic hernia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    14 / 2402 (0.58%)
    13 / 2419 (0.54%)
    27 / 4821 (0.56%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 13
    0 / 28
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dieulafoy's vascular malformation
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Diverticular perforation
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Diverticulum
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal polyp
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    2 / 2402 (0.08%)
    3 / 2419 (0.12%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    3 / 2402 (0.12%)
    2 / 2419 (0.08%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 2402 (0.04%)
    3 / 2419 (0.12%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erosive oesophagitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Faeces discoloured
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral hernia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    3 / 2402 (0.12%)
    8 / 2419 (0.33%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    4 / 2402 (0.17%)
    2 / 2419 (0.08%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    7 / 2402 (0.29%)
    3 / 2419 (0.12%)
    10 / 4821 (0.21%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    7 / 2402 (0.29%)
    1 / 2419 (0.04%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    32 / 2402 (1.33%)
    29 / 2419 (1.20%)
    61 / 4821 (1.27%)
         occurrences causally related to treatment / all
    1 / 36
    0 / 31
    1 / 67
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
    Gastrointestinal perforation
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Gastrointestinal polyp haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal ulcer
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal ulcer haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal wall thickening
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 2402 (0.12%)
    4 / 2419 (0.17%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Haematochezia
         subjects affected / exposed
    3 / 2402 (0.12%)
    4 / 2419 (0.17%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic erosive gastritis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    3 / 2402 (0.12%)
    5 / 2419 (0.21%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    3 / 2402 (0.12%)
    2 / 2419 (0.08%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Ileus paralytic
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Impaired gastric emptying
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    13 / 2402 (0.54%)
    10 / 2419 (0.41%)
    23 / 4821 (0.48%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 10
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia, obstructive
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal infarction
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Intestinal ischaemia
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Intestinal obstruction
         subjects affected / exposed
    5 / 2402 (0.21%)
    5 / 2419 (0.21%)
    10 / 4821 (0.21%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Intestinal perforation
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Intestinal polyp
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal strangulation
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intra-abdominal haematoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intra-abdominal haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Large intestine polyp
         subjects affected / exposed
    4 / 2402 (0.17%)
    5 / 2419 (0.21%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    6 / 2402 (0.25%)
    1 / 2419 (0.04%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mallory-Weiss syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    6 / 2402 (0.25%)
    7 / 2419 (0.29%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 8
    0 / 16
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Mouth haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    5 / 2402 (0.21%)
    12 / 2419 (0.50%)
    17 / 4821 (0.35%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 15
    0 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obstructive pancreatitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal perforation
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Oesophageal ulcer
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    3 / 2402 (0.12%)
    2 / 2419 (0.08%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    9 / 2402 (0.37%)
    5 / 2419 (0.21%)
    14 / 4821 (0.29%)
         occurrences causally related to treatment / all
    1 / 10
    0 / 6
    1 / 16
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    Pancreatitis chronic
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis necrotising
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis relapsing
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritoneal haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Portal hypertensive gastropathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    4 / 2402 (0.17%)
    9 / 2419 (0.37%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 11
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal polyp
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal prolapse
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Salivary gland calculus
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal haemorrhage
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    5 / 2402 (0.21%)
    7 / 2419 (0.29%)
    12 / 4821 (0.25%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 7
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toothache
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    11 / 2402 (0.46%)
    7 / 2419 (0.29%)
    18 / 4821 (0.37%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 8
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Varices oesophageal
         subjects affected / exposed
    2 / 2402 (0.08%)
    3 / 2419 (0.12%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    11 / 2402 (0.46%)
    9 / 2419 (0.37%)
    20 / 4821 (0.41%)
         occurrences causally related to treatment / all
    1 / 12
    0 / 9
    1 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    1 / 2402 (0.04%)
    5 / 2419 (0.21%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    4 / 5
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blister
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Butterfly rash
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Decubitus ulcer
         subjects affected / exposed
    1 / 2402 (0.04%)
    3 / 2419 (0.12%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Dermatitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dermatitis exfoliative generalised
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    5 / 2402 (0.21%)
    2 / 2419 (0.08%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic wound
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eczema
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eczema asteatotic
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erythema
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage subcutaneous
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperhidrosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intertrigo
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic skin ulcer
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neurodermatitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Purpura
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash pruritic
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rhinophyma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin lesion
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    3 / 2402 (0.12%)
    5 / 2419 (0.21%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous emphysema
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Urticaria
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vasculitic ulcer
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    110 / 2402 (4.58%)
    90 / 2419 (3.72%)
    200 / 4821 (4.15%)
         occurrences causally related to treatment / all
    47 / 142
    29 / 110
    76 / 252
         deaths causally related to treatment / all
    2 / 12
    2 / 9
    4 / 21
    Anuria
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Azotaemia
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Bladder diverticulum
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder neck obstruction
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder prolapse
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus bladder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus urethral
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    14 / 2402 (0.58%)
    13 / 2419 (0.54%)
    27 / 4821 (0.56%)
         occurrences causally related to treatment / all
    5 / 16
    3 / 13
    8 / 29
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    End stage renal disease
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Glomerulonephritis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glomerulonephropathy
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    8 / 2402 (0.33%)
    5 / 2419 (0.21%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 5
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage urinary tract
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    3 / 2402 (0.12%)
    2 / 2419 (0.08%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    5 / 2402 (0.21%)
    3 / 2419 (0.12%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephropathy toxic
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Nephrotic syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oliguria
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prerenal failure
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal artery stenosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cyst
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal disorder
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    29 / 2402 (1.21%)
    31 / 2419 (1.28%)
    60 / 4821 (1.24%)
         occurrences causally related to treatment / all
    5 / 33
    10 / 36
    15 / 69
         deaths causally related to treatment / all
    0 / 5
    0 / 5
    0 / 10
    Renal impairment
         subjects affected / exposed
    48 / 2402 (2.00%)
    24 / 2419 (0.99%)
    72 / 4821 (1.49%)
         occurrences causally related to treatment / all
    17 / 53
    11 / 25
    28 / 78
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Renal infarct
         subjects affected / exposed
    0 / 2402 (0.00%)
    3 / 2419 (0.12%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Renal injury
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal mass
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal pain
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal vein stenosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Ureterolithiasis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    8 / 2402 (0.33%)
    8 / 2419 (0.33%)
    16 / 4821 (0.33%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercorticoidism
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperparathyroidism
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parathyroid hyperplasia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Acquired claw toe
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    7 / 2402 (0.29%)
    4 / 2419 (0.17%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    3 / 2402 (0.12%)
    5 / 2419 (0.21%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    11 / 2402 (0.46%)
    11 / 2419 (0.45%)
    22 / 4821 (0.46%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 12
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CREST syndrome
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest wall haematoma
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chondrocalcinosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dactylitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dupuytren's contracture
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Exostosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fibromyalgia
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 2402 (0.00%)
    3 / 2419 (0.12%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 2402 (0.04%)
    3 / 2419 (0.12%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gouty arthritis
         subjects affected / exposed
    1 / 2402 (0.04%)
    3 / 2419 (0.12%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    5 / 2402 (0.21%)
    9 / 2419 (0.37%)
    14 / 4821 (0.29%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 11
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Kyphosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    5 / 2402 (0.21%)
    4 / 2419 (0.17%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mobility decreased
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscle spasms
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    4 / 2402 (0.17%)
    3 / 2419 (0.12%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myositis ossificans
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteitis deformans
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    28 / 2402 (1.17%)
    31 / 2419 (1.28%)
    59 / 4821 (1.22%)
         occurrences causally related to treatment / all
    0 / 31
    0 / 39
    0 / 70
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    6 / 2402 (0.25%)
    2 / 2419 (0.08%)
    8 / 4821 (0.17%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periarthritis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periostitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudarthrosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    3 / 2402 (0.12%)
    6 / 2419 (0.25%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Scleroderma
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Spinal osteoarthritis
         subjects affected / exposed
    4 / 2402 (0.17%)
    6 / 2419 (0.25%)
    10 / 4821 (0.21%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    6 / 2402 (0.25%)
    3 / 2419 (0.12%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    6 / 2402 (0.25%)
    5 / 2419 (0.21%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tenosynovitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal sepsis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal wall abscess
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess jaw
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Abscess oral
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acinetobacter bacteraemia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute endocarditis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Amoebiasis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    4 / 2402 (0.17%)
    2 / 2419 (0.08%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Arthritis bacterial
         subjects affected / exposed
    6 / 2402 (0.25%)
    3 / 2419 (0.12%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspergillus infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Bacteraemia
         subjects affected / exposed
    7 / 2402 (0.29%)
    6 / 2419 (0.25%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 7
    0 / 16
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Bacterial disease carrier
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial rhinitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Beta haemolytic streptococcal infection
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary sepsis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone abscess
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    41 / 2402 (1.71%)
    32 / 2419 (1.32%)
    73 / 4821 (1.51%)
         occurrences causally related to treatment / all
    0 / 50
    0 / 39
    0 / 89
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Bronchitis viral
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Campylobacter infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    25 / 2402 (1.04%)
    30 / 2419 (1.24%)
    55 / 4821 (1.14%)
         occurrences causally related to treatment / all
    0 / 35
    0 / 38
    0 / 73
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Chest wall abscess
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis infective
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Chronic sinusitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium colitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    3 / 2402 (0.12%)
    6 / 2419 (0.25%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Clostridium difficile infection
         subjects affected / exposed
    2 / 2402 (0.08%)
    3 / 2419 (0.12%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colonic abscess
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Complicated appendicitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis bacterial
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis escherichia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic gangrene
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    9 / 2402 (0.37%)
    3 / 2419 (0.12%)
    12 / 4821 (0.25%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 3
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Eczema infected
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolic pneumonia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    3 / 2402 (0.12%)
    2 / 2419 (0.08%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    Enteritis infectious
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterococcal sepsis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epiglottitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    7 / 2402 (0.29%)
    11 / 2419 (0.45%)
    18 / 4821 (0.37%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 15
    0 / 23
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Gastroenteritis
         subjects affected / exposed
    16 / 2402 (0.67%)
    21 / 2419 (0.87%)
    37 / 4821 (0.77%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 21
    0 / 37
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Gastroenteritis bacterial
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis clostridial
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal viral infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Genital herpes zoster
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma infection
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Helicobacter infection
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis E
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    4 / 2402 (0.17%)
    2 / 2419 (0.08%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hordeolum
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Human anaplasmosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    4 / 2402 (0.17%)
    2 / 2419 (0.08%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    3 / 2402 (0.12%)
    1 / 2419 (0.04%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of bronchiectasis
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    3 / 2402 (0.12%)
    2 / 2419 (0.08%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Influenza
         subjects affected / exposed
    11 / 2402 (0.46%)
    16 / 2419 (0.66%)
    27 / 4821 (0.56%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 16
    0 / 27
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Intervertebral discitis
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal sepsis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intracranial infection
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Labyrinthitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    5 / 2402 (0.21%)
    4 / 2419 (0.17%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Lower respiratory tract infection
         subjects affected / exposed
    12 / 2402 (0.50%)
    11 / 2419 (0.45%)
    23 / 4821 (0.48%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 11
    0 / 25
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Lower respiratory tract infection viral
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    11 / 2402 (0.46%)
    12 / 2419 (0.50%)
    23 / 4821 (0.48%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 13
    0 / 25
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Lymphangitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mediastinitis
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Medical device site infection
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis enterococcal
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nosocomial infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    0 / 2402 (0.00%)
    2 / 2419 (0.08%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    3 / 2402 (0.12%)
    7 / 2419 (0.29%)
    10 / 4821 (0.21%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 9
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periodontitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis bacterial
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal sepsis
         subjects affected / exposed
    0 / 2402 (0.00%)
    3 / 2419 (0.12%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Pneumonia
         subjects affected / exposed
    178 / 2402 (7.41%)
    162 / 2419 (6.70%)
    340 / 4821 (7.05%)
         occurrences causally related to treatment / all
    0 / 212
    0 / 197
    0 / 409
         deaths causally related to treatment / all
    0 / 24
    0 / 23
    0 / 47
    Pneumonia bacterial
         subjects affected / exposed
    5 / 2402 (0.21%)
    4 / 2419 (0.17%)
    9 / 4821 (0.19%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Pneumonia mycoplasmal
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 3
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Pyelonephritis
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    3 / 2402 (0.12%)
    4 / 2419 (0.17%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal abscess
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory moniliasis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchitis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    21 / 2402 (0.87%)
    19 / 2419 (0.79%)
    40 / 4821 (0.83%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 21
    0 / 46
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
    Respiratory tract infection bacterial
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    2 / 2402 (0.08%)
    1 / 2419 (0.04%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Salmonellosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    37 / 2402 (1.54%)
    34 / 2419 (1.41%)
    71 / 4821 (1.47%)
         occurrences causally related to treatment / all
    1 / 44
    0 / 41
    1 / 85
         deaths causally related to treatment / all
    0 / 9
    0 / 12
    0 / 21
    Septic encephalopathy
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic necrosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    16 / 2402 (0.67%)
    21 / 2419 (0.87%)
    37 / 4821 (0.77%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 23
    0 / 40
         deaths causally related to treatment / all
    0 / 10
    0 / 10
    0 / 20
    Severe acute respiratory syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Shunt infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin bacterial infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Staphylococcal infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syphilis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Tuberculous pleurisy
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tubo-ovarian abscess
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 2402 (0.25%)
    5 / 2419 (0.21%)
    11 / 4821 (0.23%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urethritis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    68 / 2402 (2.83%)
    54 / 2419 (2.23%)
    122 / 4821 (2.53%)
         occurrences causally related to treatment / all
    0 / 76
    0 / 68
    0 / 144
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Urosepsis
         subjects affected / exposed
    14 / 2402 (0.58%)
    11 / 2419 (0.45%)
    25 / 4821 (0.52%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 12
    0 / 26
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
    Vestibular neuronitis
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound abscess
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    3 / 2402 (0.12%)
    2 / 2419 (0.08%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    Cardiometabolic syndrome
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Decreased appetite
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Dehydration
         subjects affected / exposed
    26 / 2402 (1.08%)
    18 / 2419 (0.74%)
    44 / 4821 (0.91%)
         occurrences causally related to treatment / all
    1 / 30
    1 / 18
    2 / 48
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    Diabetes mellitus
         subjects affected / exposed
    8 / 2402 (0.33%)
    9 / 2419 (0.37%)
    17 / 4821 (0.35%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 9
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Diabetes mellitus inadequate control
         subjects affected / exposed
    3 / 2402 (0.12%)
    4 / 2419 (0.17%)
    7 / 4821 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic complication
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    9 / 2402 (0.37%)
    3 / 2419 (0.12%)
    12 / 4821 (0.25%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 3
    1 / 14
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    Electrolyte imbalance
         subjects affected / exposed
    2 / 2402 (0.08%)
    0 / 2419 (0.00%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    8 / 2402 (0.33%)
    8 / 2419 (0.33%)
    16 / 4821 (0.33%)
         occurrences causally related to treatment / all
    1 / 8
    1 / 11
    2 / 19
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Fluid retention
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Folate deficiency
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    11 / 2402 (0.46%)
    5 / 2419 (0.21%)
    16 / 4821 (0.33%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 5
    1 / 16
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Haemochromatosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperammonaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    2 / 2402 (0.08%)
    2 / 2419 (0.08%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    0 / 2419 (0.00%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    16 / 2402 (0.67%)
    10 / 2419 (0.41%)
    26 / 4821 (0.54%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 15
    0 / 33
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Hyperglycaemic hyperosmolar nonketotic syndrome
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    42 / 2402 (1.75%)
    19 / 2419 (0.79%)
    61 / 4821 (1.27%)
         occurrences causally related to treatment / all
    28 / 51
    6 / 21
    34 / 72
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    Hypernatraemia
         subjects affected / exposed
    0 / 2402 (0.00%)
    3 / 2419 (0.12%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperuricaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    6 / 2402 (0.25%)
    20 / 2419 (0.83%)
    26 / 4821 (0.54%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 20
    0 / 26
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Hypokalaemia
         subjects affected / exposed
    14 / 2402 (0.58%)
    8 / 2419 (0.33%)
    22 / 4821 (0.46%)
         occurrences causally related to treatment / all
    1 / 15
    0 / 9
    1 / 24
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hypomagnesaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    2 / 2419 (0.08%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    17 / 2402 (0.71%)
    17 / 2419 (0.70%)
    34 / 4821 (0.71%)
         occurrences causally related to treatment / all
    1 / 21
    1 / 19
    2 / 40
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoosmolar state
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    1 / 2402 (0.04%)
    4 / 2419 (0.17%)
    5 / 4821 (0.10%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 5
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency
         subjects affected / exposed
    4 / 2402 (0.17%)
    0 / 2419 (0.00%)
    4 / 4821 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Ketoacidosis
         subjects affected / exposed
    0 / 2402 (0.00%)
    1 / 2419 (0.04%)
    1 / 4821 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    3 / 2402 (0.12%)
    0 / 2419 (0.00%)
    3 / 4821 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Marasmus
         subjects affected / exposed
    1 / 2402 (0.04%)
    1 / 2419 (0.04%)
    2 / 4821 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Metabolic acidosis
         subjects affected / exposed
    3 / 2402 (0.12%)
    3 / 2419 (0.12%)
    6 / 4821 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Type 2 diabetes mellitus
         subjects affected / exposed
    8 / 2402 (0.33%)
    5 / 2419 (0.21%)
    13 / 4821 (0.27%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Valsartan LCZ696 All patients
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1995 / 2402 (83.06%)
    2005 / 2419 (82.89%)
    4000 / 4821 (82.97%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    314 / 2402 (13.07%)
    225 / 2419 (9.30%)
    539 / 4821 (11.18%)
         occurrences all number
    403
    264
    667
    Hypotension
         subjects affected / exposed
    379 / 2402 (15.78%)
    529 / 2419 (21.87%)
    908 / 4821 (18.83%)
         occurrences all number
    505
    749
    1254
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    58 / 2402 (2.41%)
    60 / 2419 (2.48%)
    118 / 4821 (2.45%)
         occurrences all number
    62
    71
    133
    Fatigue
         subjects affected / exposed
    107 / 2402 (4.45%)
    98 / 2419 (4.05%)
    205 / 4821 (4.25%)
         occurrences all number
    118
    115
    233
    Non-cardiac chest pain
         subjects affected / exposed
    92 / 2402 (3.83%)
    98 / 2419 (4.05%)
    190 / 4821 (3.94%)
         occurrences all number
    103
    115
    218
    Oedema peripheral
         subjects affected / exposed
    183 / 2402 (7.62%)
    166 / 2419 (6.86%)
    349 / 4821 (7.24%)
         occurrences all number
    221
    202
    423
    Pyrexia
         subjects affected / exposed
    54 / 2402 (2.25%)
    59 / 2419 (2.44%)
    113 / 4821 (2.34%)
         occurrences all number
    65
    76
    141
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    68 / 2402 (2.83%)
    57 / 2419 (2.36%)
    125 / 4821 (2.59%)
         occurrences all number
    86
    69
    155
    Cough
         subjects affected / exposed
    146 / 2402 (6.08%)
    188 / 2419 (7.77%)
    334 / 4821 (6.93%)
         occurrences all number
    174
    234
    408
    Dyspnoea
         subjects affected / exposed
    236 / 2402 (9.83%)
    217 / 2419 (8.97%)
    453 / 4821 (9.40%)
         occurrences all number
    291
    262
    553
    Epistaxis
         subjects affected / exposed
    71 / 2402 (2.96%)
    42 / 2419 (1.74%)
    113 / 4821 (2.34%)
         occurrences all number
    85
    46
    131
    Psychiatric disorders
    Depression
         subjects affected / exposed
    70 / 2402 (2.91%)
    68 / 2419 (2.81%)
    138 / 4821 (2.86%)
         occurrences all number
    71
    69
    140
    Insomnia
         subjects affected / exposed
    54 / 2402 (2.25%)
    75 / 2419 (3.10%)
    129 / 4821 (2.68%)
         occurrences all number
    56
    85
    141
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    65 / 2402 (2.71%)
    63 / 2419 (2.60%)
    128 / 4821 (2.66%)
         occurrences all number
    77
    70
    147
    Glomerular filtration rate decreased
         subjects affected / exposed
    93 / 2402 (3.87%)
    85 / 2419 (3.51%)
    178 / 4821 (3.69%)
         occurrences all number
    116
    101
    217
    Weight decreased
         subjects affected / exposed
    82 / 2402 (3.41%)
    71 / 2419 (2.94%)
    153 / 4821 (3.17%)
         occurrences all number
    90
    74
    164
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    72 / 2402 (3.00%)
    57 / 2419 (2.36%)
    129 / 4821 (2.68%)
         occurrences all number
    83
    62
    145
    Fall
         subjects affected / exposed
    90 / 2402 (3.75%)
    106 / 2419 (4.38%)
    196 / 4821 (4.07%)
         occurrences all number
    127
    128
    255
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    82 / 2402 (3.41%)
    87 / 2419 (3.60%)
    169 / 4821 (3.51%)
         occurrences all number
    104
    105
    209
    Atrial fibrillation
         subjects affected / exposed
    239 / 2402 (9.95%)
    248 / 2419 (10.25%)
    487 / 4821 (10.10%)
         occurrences all number
    297
    318
    615
    Bradycardia
         subjects affected / exposed
    85 / 2402 (3.54%)
    53 / 2419 (2.19%)
    138 / 4821 (2.86%)
         occurrences all number
    90
    57
    147
    Cardiac failure
         subjects affected / exposed
    269 / 2402 (11.20%)
    225 / 2419 (9.30%)
    494 / 4821 (10.25%)
         occurrences all number
    376
    304
    680
    Palpitations
         subjects affected / exposed
    56 / 2402 (2.33%)
    62 / 2419 (2.56%)
    118 / 4821 (2.45%)
         occurrences all number
    66
    70
    136
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    192 / 2402 (7.99%)
    229 / 2419 (9.47%)
    421 / 4821 (8.73%)
         occurrences all number
    213
    298
    511
    Headache
         subjects affected / exposed
    126 / 2402 (5.25%)
    114 / 2419 (4.71%)
    240 / 4821 (4.98%)
         occurrences all number
    139
    131
    270
    Syncope
         subjects affected / exposed
    62 / 2402 (2.58%)
    42 / 2419 (1.74%)
    104 / 4821 (2.16%)
         occurrences all number
    73
    50
    123
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    214 / 2402 (8.91%)
    166 / 2419 (6.86%)
    380 / 4821 (7.88%)
         occurrences all number
    242
    182
    424
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    60 / 2402 (2.50%)
    77 / 2419 (3.18%)
    137 / 4821 (2.84%)
         occurrences all number
    64
    83
    147
    Eye disorders
    Cataract
         subjects affected / exposed
    70 / 2402 (2.91%)
    84 / 2419 (3.47%)
    154 / 4821 (3.19%)
         occurrences all number
    83
    105
    188
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    54 / 2402 (2.25%)
    53 / 2419 (2.19%)
    107 / 4821 (2.22%)
         occurrences all number
    58
    57
    115
    Constipation
         subjects affected / exposed
    86 / 2402 (3.58%)
    100 / 2419 (4.13%)
    186 / 4821 (3.86%)
         occurrences all number
    93
    108
    201
    Diarrhoea
         subjects affected / exposed
    180 / 2402 (7.49%)
    177 / 2419 (7.32%)
    357 / 4821 (7.41%)
         occurrences all number
    212
    214
    426
    Nausea
         subjects affected / exposed
    87 / 2402 (3.62%)
    93 / 2419 (3.84%)
    180 / 4821 (3.73%)
         occurrences all number
    106
    100
    206
    Vomiting
         subjects affected / exposed
    58 / 2402 (2.41%)
    70 / 2419 (2.89%)
    128 / 4821 (2.66%)
         occurrences all number
    65
    78
    143
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    51 / 2402 (2.12%)
    46 / 2419 (1.90%)
    97 / 4821 (2.01%)
         occurrences all number
    55
    56
    111
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    65 / 2402 (2.71%)
    64 / 2419 (2.65%)
    129 / 4821 (2.68%)
         occurrences all number
    85
    83
    168
    Chronic kidney disease
         subjects affected / exposed
    50 / 2402 (2.08%)
    33 / 2419 (1.36%)
    83 / 4821 (1.72%)
         occurrences all number
    56
    36
    92
    Haematuria
         subjects affected / exposed
    77 / 2402 (3.21%)
    71 / 2419 (2.94%)
    148 / 4821 (3.07%)
         occurrences all number
    84
    79
    163
    Renal failure
         subjects affected / exposed
    108 / 2402 (4.50%)
    85 / 2419 (3.51%)
    193 / 4821 (4.00%)
         occurrences all number
    138
    94
    232
    Renal impairment
         subjects affected / exposed
    331 / 2402 (13.78%)
    287 / 2419 (11.86%)
    618 / 4821 (12.82%)
         occurrences all number
    414
    347
    761
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    153 / 2402 (6.37%)
    152 / 2419 (6.28%)
    305 / 4821 (6.33%)
         occurrences all number
    186
    178
    364
    Back pain
         subjects affected / exposed
    170 / 2402 (7.08%)
    149 / 2419 (6.16%)
    319 / 4821 (6.62%)
         occurrences all number
    191
    166
    357
    Muscle spasms
         subjects affected / exposed
    49 / 2402 (2.04%)
    36 / 2419 (1.49%)
    85 / 4821 (1.76%)
         occurrences all number
    56
    39
    95
    Musculoskeletal pain
         subjects affected / exposed
    58 / 2402 (2.41%)
    63 / 2419 (2.60%)
    121 / 4821 (2.51%)
         occurrences all number
    63
    69
    132
    Osteoarthritis
         subjects affected / exposed
    92 / 2402 (3.83%)
    92 / 2419 (3.80%)
    184 / 4821 (3.82%)
         occurrences all number
    105
    112
    217
    Pain in extremity
         subjects affected / exposed
    75 / 2402 (3.12%)
    81 / 2419 (3.35%)
    156 / 4821 (3.24%)
         occurrences all number
    84
    87
    171
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    197 / 2402 (8.20%)
    177 / 2419 (7.32%)
    374 / 4821 (7.76%)
         occurrences all number
    234
    217
    451
    Cellulitis
         subjects affected / exposed
    41 / 2402 (1.71%)
    61 / 2419 (2.52%)
    102 / 4821 (2.12%)
         occurrences all number
    50
    68
    118
    Influenza
         subjects affected / exposed
    109 / 2402 (4.54%)
    110 / 2419 (4.55%)
    219 / 4821 (4.54%)
         occurrences all number
    120
    130
    250
    Nasopharyngitis
         subjects affected / exposed
    177 / 2402 (7.37%)
    207 / 2419 (8.56%)
    384 / 4821 (7.97%)
         occurrences all number
    243
    272
    515
    Pneumonia
         subjects affected / exposed
    97 / 2402 (4.04%)
    100 / 2419 (4.13%)
    197 / 4821 (4.09%)
         occurrences all number
    114
    105
    219
    Respiratory tract infection
         subjects affected / exposed
    60 / 2402 (2.50%)
    48 / 2419 (1.98%)
    108 / 4821 (2.24%)
         occurrences all number
    74
    54
    128
    Upper respiratory tract infection
         subjects affected / exposed
    139 / 2402 (5.79%)
    145 / 2419 (5.99%)
    284 / 4821 (5.89%)
         occurrences all number
    185
    197
    382
    Urinary tract infection
         subjects affected / exposed
    268 / 2402 (11.16%)
    243 / 2419 (10.05%)
    511 / 4821 (10.60%)
         occurrences all number
    382
    328
    710
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    62 / 2402 (2.58%)
    52 / 2419 (2.15%)
    114 / 4821 (2.36%)
         occurrences all number
    65
    57
    122
    Gout
         subjects affected / exposed
    88 / 2402 (3.66%)
    76 / 2419 (3.14%)
    164 / 4821 (3.40%)
         occurrences all number
    106
    100
    206
    Hyperkalaemia
         subjects affected / exposed
    298 / 2402 (12.41%)
    238 / 2419 (9.84%)
    536 / 4821 (11.12%)
         occurrences all number
    423
    325
    748
    Hyperuricaemia
         subjects affected / exposed
    75 / 2402 (3.12%)
    62 / 2419 (2.56%)
    137 / 4821 (2.84%)
         occurrences all number
    83
    65
    148
    Hypokalaemia
         subjects affected / exposed
    100 / 2402 (4.16%)
    110 / 2419 (4.55%)
    210 / 4821 (4.36%)
         occurrences all number
    128
    134
    262

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Jun 2014
    The main purpose of this amendment was to increase the contraception period for women of child-bearing potential after being taken off study medication from 4 days to 7 days in exclusion criterion 33 in order to be consistent with the other study protocols from the LCZ696 clinical program and with the LCZ696 Investigators’ Brochure. Updated TOPCAT study results and DMC’s decision to stop PARADIGM study ahead of schedule in March 2014 based on the positive efficacy findings are included in the background of the study in Introduction.
    06 May 2015
    Modified several study objectives and endpoints (secondary and exploratory endpoints) and their associated analysis plans, included cognitive function assessments using the Mini-Mental State Examination (MMSE) instrument at baseline and annually thereafter, modified several entry criteria, moved the interim efficacy analysis to occur when approximately two-thirds of the primary composite events, rather than half as previously defined and eliminated the futility analysis.
    04 Dec 2015
    Administered KCCQ at the start of the run-in (i.e., Visit 101 or 102), whichever occurs first. Included a process for conducting a medical review of medical history of enrolled patients by a Novartis central review group to assess adherence to the inclusion/exclusion criteria. Adjust sample size from 4300 to 4600 to increase the statistical power from 81% to 85% to detect a 25% reduction in recurrent heart failure hospitalizations.
    09 Dec 2015
    The purpose of this amendment was to include changes required by the Japanese Health Authority (PMDA) and the Indian Health Authority. Changes made were only applicable to Japan and India.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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