PALbociclib CoLlaborative Adjuvant Study (PALLAS)

• ClinicalTrials.gov Identifier: NCT02513394
• Recruitment Status: Active, not recruiting
• First Posted: July 31, 2015
• Results First Posted: April 13, 2022
• Last Update Posted: January 24, 2024
• Sponsor: Alliance Foundation Trials, LLC.
• Collaborators: Austrian Breast & Colorectal Cancer Study Group; NSABP Foundation Inc; PrECOG, LLC.; Breast International Group; Pfizer
• Information provided by (Responsible Party): Alliance Foundation Trials, LLC.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer
• Interventions: Drug: Palbociclib; Drug: Standard Adjuvant Endocrine Therapy
• Enrollment: 5796

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Period Title: Overall Study
Started	2896	2900
Completed	2884	2877
Not Completed	12	23
Reason Not Completed
Withdrawal by Subject	11	23
Ineligible	1	0

Baseline Characteristics

Arm/Group Title		Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)	Total
Arm/Group Description		Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.	Total of all reporting groups
Overall Number of Baseline Participants		2884	2877	5761
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	2884 participants	2877 participants	5761 participants
		52; (25 to 90)	52; (22 to 85)	52; (22 to 90)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2884 participants	2877 participants	5761 participants
	Female	2867 99.4%	2858 99.3%	5725 99.4%
	Male	17 0.6%	19 0.7%	36 0.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2884 participants	2877 participants	5761 participants
	Hispanic or Latino	138 4.8%	127 4.4%	265 4.6%
	Not Hispanic or Latino	2504 86.8%	2532 88.0%	5036 87.4%
	Unknown or Not Reported	242 8.4%	218 7.6%	460 8.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	2884 participants	2877 participants	5761 participants
	Asain	138 4.8%	141 4.9%	279 4.8%
	Black or African American/African Heritage	74 2.6%	75 2.6%	149 2.6%
	White	2521 87.4%	2498 86.8%	5019 87.1%
	Native Hawaiian or other Pacific Islander	4 0.1%	8 0.3%	12 0.2%
	American Indian or Alaska Native	14 0.5%	22 0.8%	36 0.6%
	Other	37 1.3%	36 1.3%	73 1.3%
	Unknown	96 3.3%	97 3.4%	193 3.4%

Outcome Measures

1. Primary Outcome

Title	Invasive Disease Free Survival (iDFS)
Description	Invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description:	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Overall Number of Participants Analyzed	2884	2877
Measure Type: Number; Unit of Measure: percentage of participants
	84.2	84.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib Plus Endocrine Therapy (Arm A), Endocrine Therapy Alone (Arm B)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.65
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.14
	Estimation Comments	This two sided p value was stratified by (neo)adjuvant chemotherapy (yes vs no) and age (<=50 vs >50).

2. Secondary Outcome

Title	Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin.
Description	Invasive disease-free survival (iDFS, excluding second primary invasive cancers of non-breast origin) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS excluding second primary invasive cancers of non-breast origin is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. Second primary invasive cancers of non-breast origin will not be considered as events for this endpoint. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description:	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Overall Number of Participants Analyzed	2884	2877
Measure Type: Number; Unit of Measure: percentage of patients
	85.4	86.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib Plus Endocrine Therapy (Arm A), Endocrine Therapy Alone (Arm B)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.19
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Distant Recurrence-free Survival (DRFS)
Description	Compare time to distant recurrence-free survival (DRFS). Distant recurrence is defined according to STEEP criteria as the time from randomization to the date of the first event: distant recurrence or death from any cause. Patients with a locoregional recurrence will continue to be followed for DRFS. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, or death whichever came first. Direct comparison between arms used time to DRFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered DRFS at 4 years is reported.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description:	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Overall Number of Participants Analyzed	2884	2877
Measure Type: Number; Unit of Measure: percentage of patients
	86.2	87.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib Plus Endocrine Therapy (Arm A), Endocrine Therapy Alone (Arm B)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.28
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Compare overall survival (OS). Overall survival is defined as the time period between randomization and death. Surviving patients classified as lost-to-follow up or having withdrawn consent to be followed will be censored at their date of last contact or withdrawal of consent to be followed, whichever occurs first.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description:	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Overall Number of Participants Analyzed	2884	2877
Measure Type: Number; Unit of Measure: percentage of patients
	93.8	95.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib Plus Endocrine Therapy (Arm A), Endocrine Therapy Alone (Arm B)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.78
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Locoregional Recurrences-free Survival (LRRFS)
Description	Compare locoregional recurrence-free survival (LRRFS). LRRFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, or death from any cause. Patients with second primary invasive cancers of non-breast origin or distant recurrence will be censored at the date of diagnosis. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description:	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Overall Number of Participants Analyzed	2884	2877
Measure Type: Number; Unit of Measure: percentage of patients
	96.8	95.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib Plus Endocrine Therapy (Arm A), Endocrine Therapy Alone (Arm B)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.23
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	4 years
Adverse Event Reporting Description	The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)		Endocrine Therapy Alone (Arm B)
Arm/Group Description	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.		Standard adjuvant endocrine therapy for a duration of at least 5 years.
All-Cause Mortality
	Palbociclib Plus Endocrine Therapy (Arm A)		Endocrine Therapy Alone (Arm B)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	99/2841 (3.48%)		76/2902 (2.62%)
Serious Adverse Events
	Palbociclib Plus Endocrine Therapy (Arm A)		Endocrine Therapy Alone (Arm B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	369/2841 (12.99%)		229/2902 (7.89%)
Blood and lymphatic system disorders
Anaemia † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Anaemia macrocytic † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Febrile neutropenia † 1	13/2841 (0.46%)	13	0/2902 (0.00%)	0
Leukocytosis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Lymphadenitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Neutropenia † 1	4/2841 (0.14%)	5	0/2902 (0.00%)	0
Pancytopenia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Splenic infarction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cardiac disorders
Acute coronary syndrome † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Acute myocardial infarction † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Angina pectoris † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Arteriospasm coronary † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Atrial fibrillation † 1	2/2841 (0.07%)	2	4/2902 (0.14%)	4
Atrioventricular block † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Atrioventricular block complete † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cardiac arrest † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cardiac failure † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Cardiac failure acute † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cardiac failure congestive † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Cardiac ventricular thrombosis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cardiomyopathy † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Coronary artery disease † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Extrasystoles † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Left ventricular failure † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Myocardial ischaemia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Palpitations † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Sinus bradycardia † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Stress cardiomyopathy † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Supraventricular tachycardia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Congenital, familial and genetic disorders
Atrial septal defect † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Gene mutation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ear and labyrinth disorders
Deafness unilateral † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vertigo † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Vertigo positional † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Endocrine disorders
Goitre † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Hyperparathyroidism † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hypothyroidism † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Eye disorders
Cataract † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Diplopia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Eyelid function disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Maculopathy † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gastrointestinal disorders
Abdominal hernia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Abdominal pain † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Abdominal pain upper † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Colitis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Colitis ischaemic † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Diarrhoea † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Duodenal ulcer † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Duodenitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Enteritis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gastrooesophageal reflux disease † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Ileus † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Intestinal obstruction † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Intestinal perforation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Intussusception † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Large intestine perforation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Large intestine polyp † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nausea † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Neutropenic colitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oedematous pancreatitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oesophagitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pancreatitis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Peritoneal perforation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Small intestinal obstruction † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Volvulus of small bowel † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vomiting † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
General disorders
Capsular contracture associated with breast implant † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Chest discomfort † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Chest pain † 1	3/2841 (0.11%)	5	1/2902 (0.03%)	1
Death † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Disease progression † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	4
Disease recurrence † 1	1/2841 (0.04%)	2	1/2902 (0.03%)	1
Dysplasia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Fatigue † 1	2/2841 (0.07%)	3	0/2902 (0.00%)	0
Hypothermia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Impaired healing † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Implant site fibrosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Influenza like illness † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Infusion site extravasation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Non-cardiac chest pain † 1	4/2841 (0.14%)	4	0/2902 (0.00%)	0
Pyrexia † 1	3/2841 (0.11%)	4	1/2902 (0.03%)	1
Hepatobiliary disorders
Acute hepatic failure † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bile duct stone † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cholangitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cholecystitis † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Cholecystitis acute † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cholelithiasis † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	2
Drug-induced liver injury † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hepatic failure † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hepatitis acute † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Immune system disorders
Anaphylactic reaction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Infections and infestations
Anal abscess † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Anorectal infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Appendiceal abscess † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Appendicitis † 1	3/2841 (0.11%)	3	5/2902 (0.17%)	5
Appendicitis perforated † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Bacterial infection † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Breast abscess † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Breast cellulitis † 1	16/2841 (0.56%)	17	10/2902 (0.34%)	10
Bronchitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
COVID-19 pneumonia † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	2
Campylobacter infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cellulitis † 1	24/2841 (0.84%)	26	9/2902 (0.31%)	10
Cystitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Device related infection † 1	2/2841 (0.07%)	2	4/2902 (0.14%)	4
Disseminated varicella zoster virus infection † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Diverticulitis † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Erysipelas † 1	5/2841 (0.18%)	5	0/2902 (0.00%)	0
Erysipelothrix sepsis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Escherichia pyelonephritis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Escherichia sepsis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gastroenteritis † 1	4/2841 (0.14%)	4	3/2902 (0.10%)	3
Gastroenteritis norovirus † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Gastroenteritis viral † 1	4/2841 (0.14%)	4	0/2902 (0.00%)	0
Herpes zoster † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Infected seroma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Infection † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	4
Influenza † 1	16/2841 (0.56%)	16	2/2902 (0.07%)	2
Laryngitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Listeria sepsis † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Localised infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lower respiratory tract infection † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Mastitis † 1	13/2841 (0.46%)	14	10/2902 (0.34%)	11
Paronychia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pelvic inflammatory disease † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Peritonitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pneumonia † 1	16/2841 (0.56%)	18	7/2902 (0.24%)	8
Postoperative wound infection † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Pyelonephritis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Pyelonephritis acute † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Respiratory tract infection † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Sepsis † 1	8/2841 (0.28%)	9	3/2902 (0.10%)	3
Septic shock † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Sinusitis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Skin infection † 1	8/2841 (0.28%)	8	0/2902 (0.00%)	0
Soft tissue infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Staphylococcal bacteraemia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Staphylococcal infection † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Upper respiratory tract infection † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	3
Urinary tract infection † 1	8/2841 (0.28%)	8	3/2902 (0.10%)	3
Urosepsis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vascular device infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vestibular neuronitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Viral infection † 1	4/2841 (0.14%)	4	0/2902 (0.00%)	0
Viral labyrinthitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Viral pericarditis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vulvovaginal candidiasis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Wound abscess † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Wound infection † 1	3/2841 (0.11%)	4	4/2902 (0.14%)	4
Injury, poisoning and procedural complications
Abdominal wound dehiscence † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Alcohol poisoning † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Animal bite † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Ankle fracture † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Brain contusion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Breast procedural complication † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Clavicle fracture † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Concussion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Craniocerebral injury † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Fall † 1	3/2841 (0.11%)	3	3/2902 (0.10%)	4
Head injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hip fracture † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Humerus fracture † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Limb injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lower limb fracture † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Meniscus injury † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Open fracture † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Post procedural haematoma † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Postoperative wound complication † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Procedural complication † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Radiation pneumonitis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Radius fracture † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Rib fracture † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Seroma † 1	3/2841 (0.11%)	4	4/2902 (0.14%)	4
Skin flap necrosis † 1	1/2841 (0.04%)	3	0/2902 (0.00%)	0
Spinal fracture † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	3
Sternal fracture † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Subdural haematoma † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Thermal burn † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Thoracic vertebral fracture † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Upper limb fracture † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vaginal cuff dehiscence † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vascular access site thrombosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Wound complication † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Wound dehiscence † 1	9/2841 (0.32%)	9	5/2902 (0.17%)	5
Wrist fracture † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Investigations
Alanine aminotransferase increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Blood bilirubin increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Liver function test increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Neutrophil count decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Troponin increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
White blood cell count decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Metabolism and nutrition disorders
Dehydration † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hypercalcaemia † 1	1/2841 (0.04%)	2	1/2902 (0.03%)	1
Hypoglycaemia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hypokalaemia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hyponatraemia † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/2841 (0.04%)	1	4/2902 (0.14%)	5
Arthritis † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Back pain † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Flank pain † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Foot deformity † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	3
Haemarthrosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Intervertebral disc protrusion † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Joint range of motion decreased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Osteoarthritis † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	4
Pain in extremity † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Rotator cuff syndrome † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Soft tissue necrosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Spinal synovial cyst † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Tendonitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Acute promyelocytic leukaemia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Adenocarcinoma pancreas † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
B-cell small lymphocytic lymphoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Basal cell carcinoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Benign breast neoplasm † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bladder neoplasm † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Breast cancer metastatic † 1	2/2841 (0.07%)	3	1/2902 (0.03%)	1
Breast cancer recurrent † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cervix carcinoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cervix carcinoma stage 0 † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Colon cancer † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Endometrial adenocarcinoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Intraductal papillary-mucinous carcinoma of pancreas † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lung neoplasm malignant † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Lymphoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lymphoplasmacytoid lymphoma/immunocytoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Malignant melanoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Malignant melanoma in situ † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Metastatic malignant melanoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Ovarian adenoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Renal cell carcinoma † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Salivary gland adenoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Second primary malignancy † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Small cell carcinoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Squamous cell carcinoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Squamous cell carcinoma of the tongue † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Thyroid adenoma † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Uterine leiomyoma † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Uterine leiomyosarcoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Uveal melanoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Nervous system disorders
Ageusia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Aphasia † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Carotid artery stenosis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Carpal tunnel syndrome † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cerebral infarction † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cerebral ischaemia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cerebrovascular accident † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Dizziness † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Encephalopathy † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Epilepsy † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Facial paralysis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Haemorrhage intracranial † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Headache † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
IIIrd nerve disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Intercostal neuralgia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Ischaemic stroke † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Myasthenia gravis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Paraesthesia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Presyncope † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Ruptured cerebral aneurysm † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Subarachnoid haemorrhage † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Syncope † 1	2/2841 (0.07%)	2	4/2902 (0.14%)	4
Transient ischaemic attack † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
VIth nerve paralysis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vertigo CNS origin † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Product Issues
Device breakage † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Device dislocation † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	3
Device leakage † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Psychiatric disorders
Alcohol abuse † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Alcohol use disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Alcohol withdrawal syndrome † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Anxiety † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Confusional state † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Delusion † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Depression † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Drug abuse † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Mania † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mental disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Mental status changes † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Panic attack † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Paranoia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Psychotic disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Suicidal ideation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Suicide attempt † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	4
Renal and urinary disorders
Acute kidney injury † 1	4/2841 (0.14%)	5	1/2902 (0.03%)	1
Chronic kidney disease † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nephrolithiasis † 1	1/2841 (0.04%)	1	4/2902 (0.14%)	4
Renal colic † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Subcapsular renal haematoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Ureteric obstruction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ureteric stenosis † 1	1/2841 (0.04%)	4	0/2902 (0.00%)	0
Ureterolithiasis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Reproductive system and breast disorders
Adnexa uteri cyst † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Breast calcifications † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Breast cyst † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Breast haematoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Breast necrosis † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Breast swelling † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cervical cyst † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Endometrial disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Endometrial hyperplasia † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Endometrial hypertrophy † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Endometrial thickening † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Endometriosis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ovarian cyst † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Uterine polyp † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Uterine prolapse † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Vaginal haematoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vaginal prolapse † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Acute respiratory failure † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Asthma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Asthma-chronic obstructive pulmonary disease overlap syndrome † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bronchospasm † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Chronic obstructive pulmonary disease † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Dyspnoea † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Hypoxia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Laryngeal stenosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pleural effusion † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Pleurisy † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Pneumonitis † 1	4/2841 (0.14%)	4	0/2902 (0.00%)	0
Pulmonary embolism † 1	13/2841 (0.46%)	13	5/2902 (0.17%)	5
Pulmonary fibrosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pulmonary haemorrhage † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pulmonary oedema † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pulmonary sarcoidosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Respiratory disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Respiratory failure † 1	1/2841 (0.04%)	2	1/2902 (0.03%)	2
Vocal cord dysfunction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vocal cord polyp † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Skin and subcutaneous tissue disorders
Keloid scar † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Skin necrosis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Urticaria † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vascular disorders
Axillary vein thrombosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Deep vein thrombosis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Embolism † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	2
Hypertensive crisis † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Hypotension † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Lymphoedema † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Peripheral ischaemia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Palbociclib Plus Endocrine Therapy (Arm A)		Endocrine Therapy Alone (Arm B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2824/2841 (99.40%)		2600/2902 (89.59%)
Blood and lymphatic system disorders
Agranulocytosis † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Anaemia † 1	634/2841 (22.32%)	1161	147/2902 (5.07%)	211
Anaemia macrocytic † 1	4/2841 (0.14%)	6	0/2902 (0.00%)	0
Anaemia vitamin B12 deficiency † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Blood disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Bone marrow oedema † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Eosinophilia † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Febrile neutropenia † 1	16/2841 (0.56%)	16	0/2902 (0.00%)	0
Haematotoxicity † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Haemorrhagic diathesis † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Increased tendency to bruise † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Iron deficiency anaemia † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Leukocytosis † 1	2/2841 (0.07%)	6	1/2902 (0.03%)	1
Leukopenia † 1	397/2841 (13.97%)	1798	64/2902 (2.21%)	98
Lymph node pain † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Lymphadenitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lymphadenopathy † 1	6/2841 (0.21%)	6	10/2902 (0.34%)	12
Lymphadenopathy mediastinal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lymphatic disorder † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Lymphopenia † 1	58/2841 (2.04%)	184	24/2902 (0.83%)	40
Macrocytosis † 1	7/2841 (0.25%)	7	0/2902 (0.00%)	0
Microcytosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Monocytopenia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Myelosuppression † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Neutropenia † 1	1125/2841 (39.60%)	5381	76/2902 (2.62%)	112
Pancytopenia † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Polycythaemia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Thrombocytopenia † 1	195/2841 (6.86%)	403	15/2902 (0.52%)	18
Thrombocytosis † 1	4/2841 (0.14%)	4	0/2902 (0.00%)	0
White blood cell disorder † 1	2/2841 (0.07%)	4	0/2902 (0.00%)	0
Cardiac disorders
Acute left ventricular failure † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Angina pectoris † 1	4/2841 (0.14%)	4	0/2902 (0.00%)	0
Arrhythmia † 1	2/2841 (0.07%)	4	2/2902 (0.07%)	2
Atrial fibrillation † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Atrial thrombosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Bradycardia † 1	2/2841 (0.07%)	2	5/2902 (0.17%)	5
Bundle branch block right † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Cardiac failure † 1	3/2841 (0.11%)	3	3/2902 (0.10%)	3
Cardiac failure chronic † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cardiac failure congestive † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Cardiac flutter † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cardiac ventricular thrombosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cardiomyopathy † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Cardiovascular disorder † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Chronic left ventricular failure † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Coronary artery disease † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Extrasystoles † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Left ventricular dysfunction † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Left ventricular failure † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mitral valve disease † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Palpitations † 1	46/2841 (1.62%)	52	38/2902 (1.31%)	39
Pericarditis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Sinus arrhythmia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Sinus bradycardia † 1	4/2841 (0.14%)	4	4/2902 (0.14%)	5
Sinus tachycardia † 1	13/2841 (0.46%)	14	12/2902 (0.41%)	17
Supraventricular tachycardia † 1	5/2841 (0.18%)	5	1/2902 (0.03%)	1
Systolic dysfunction † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Tachyarrhythmia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Tachycardia † 1	17/2841 (0.60%)	19	29/2902 (1.00%)	31
Tachycardia induced cardiomyopathy † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ventricular arrhythmia † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Ventricular extrasystoles † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Congenital, familial and genetic disorders
Developmental hip dysplasia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Gilbert's syndrome † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hereditary haemochromatosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hyper IgM syndrome † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ear and labyrinth disorders
Veritgo † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cerumen impaction † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Deafness † 1	4/2841 (0.14%)	4	7/2902 (0.24%)	8
Deafness unilateral † 1	2/2841 (0.07%)	3	2/2902 (0.07%)	2
Ear congestion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Ear discomfort † 1	5/2841 (0.18%)	5	4/2902 (0.14%)	4
Ear disorder † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Ear pain † 1	40/2841 (1.41%)	43	11/2902 (0.38%)	11
Ear pruritus † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Eustachian tube patulous † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Excessive cerumen production † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
External ear inflammation † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
External ear pain † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hyperacusis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Hypoacusis † 1	9/2841 (0.32%)	10	1/2902 (0.03%)	1
Middle ear inflammation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Motion sickness † 1	1/2841 (0.04%)	2	2/2902 (0.07%)	2
Otorrhoea † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Tinnitus † 1	23/2841 (0.81%)	24	20/2902 (0.69%)	20
Tympanic membrane perforation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vertigo † 1	74/2841 (2.60%)	84	38/2902 (1.31%)	40
Vertigo positional † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Vestibular disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Endocrine disorders
Autoimmune thyroiditis † 1	2/2841 (0.07%)	2	4/2902 (0.14%)	5
Goitre † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Hyperparathyroidism † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Hyperthyroidism † 1	5/2841 (0.18%)	5	3/2902 (0.10%)	3
Hypothyroidism † 1	21/2841 (0.74%)	22	41/2902 (1.41%)	44
Thyroid mass † 1	4/2841 (0.14%)	4	7/2902 (0.24%)	7
Thyroid pain † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Eye disorders
Asthenopia † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Blepharitis † 1	5/2841 (0.18%)	5	2/2902 (0.07%)	2
Blepharospasm † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Blindness † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Blindness transient † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Cataract † 1	16/2841 (0.56%)	20	19/2902 (0.65%)	22
Cataract nuclear † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Chalazion † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Choroidal effusion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Conjunctival disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Conjunctival haemorrhage † 1	6/2841 (0.21%)	6	4/2902 (0.14%)	4
Conjunctivitis allergic † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Corneal thickening † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Dacryostenosis acquired † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Diplopia † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Dry eye † 1	68/2841 (2.39%)	75	42/2902 (1.45%)	48
Eye disorder † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Eye haemorrhage † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Eye inflammation † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Eye irritation † 1	5/2841 (0.18%)	5	2/2902 (0.07%)	2
Eye oedema † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Eye pain † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Eye pruritus † 1	10/2841 (0.35%)	11	5/2902 (0.17%)	6
Eye swelling † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Eyelid cyst † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Eyelid disorder † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Eyelid function disorder † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Eyelid oedema † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Eyelid ptosis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Eyelids pruritus † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Glaucoma † 1	3/2841 (0.11%)	3	3/2902 (0.10%)	3
Iritis † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Keratitis † 1	4/2841 (0.14%)	8	0/2902 (0.00%)	0
Keratopathy † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Lacrimal cyst † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lacrimation increased † 1	96/2841 (3.38%)	105	6/2902 (0.21%)	6
Macular degeneration † 1	3/2841 (0.11%)	4	3/2902 (0.10%)	3
Macular fibrosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mydriasis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Neovascular age-related macular degeneration † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Ocular hyperaemia † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Orbital haemorrhage † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Orbital oedema † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pars plana cyst † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Periorbital oedema † 1	2/2841 (0.07%)	4	0/2902 (0.00%)	0
Periorbital swelling † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Photophobia † 1	4/2841 (0.14%)	4	3/2902 (0.10%)	3
Photopsia † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Presbyopia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Punctate keratitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Retinal detachment † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Retinal dystrophy † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Retinal haemorrhage † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Retinal tear † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	3
Retinoschisis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Scleral cyst † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Swelling of eyelid † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Ulcerative keratitis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Uveitis † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	2
Vision blurred † 1	69/2841 (2.43%)	75	36/2902 (1.24%)	40
Visual acuity reduced † 1	6/2841 (0.21%)	6	4/2902 (0.14%)	4
Visual impairment † 1	19/2841 (0.67%)	19	11/2902 (0.38%)	11
Visual snow syndrome † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vitreous detachment † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Vitreous floaters † 1	6/2841 (0.21%)	6	10/2902 (0.34%)	10
Xerophthalmia † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	2
Gastrointestinal disorders
Abdominal discomfort † 1	22/2841 (0.77%)	27	16/2902 (0.55%)	16
Abdominal distension † 1	30/2841 (1.06%)	36	33/2902 (1.14%)	35
Abdominal mass † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Abdominal pain † 1	153/2841 (5.39%)	190	110/2902 (3.79%)	134
Abdominal pain lower † 1	14/2841 (0.49%)	14	16/2902 (0.55%)	17
Abdominal pain upper † 1	84/2841 (2.96%)	103	53/2902 (1.83%)	61
Abdominal rigidity † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Abdominal tenderness † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Abdominal wall haematoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Anal fissure † 1	12/2841 (0.42%)	16	3/2902 (0.10%)	3
Anal fistula † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Anal haemorrhage † 1	11/2841 (0.39%)	12	1/2902 (0.03%)	1
Anal incontinence † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Anal inflammation † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Anal pruritus † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Anal skin tags † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Angular cheilitis † 1	4/2841 (0.14%)	6	2/2902 (0.07%)	2
Aphthous ulcer † 1	16/2841 (0.56%)	17	3/2902 (0.10%)	3
Apical granuloma † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Ascites † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Barrett's oesophagus † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Bowel movement irregularity † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Change of bowel habit † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Cheilitis † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Chronic gastritis † 1	2/2841 (0.07%)	3	2/2902 (0.07%)	2
Colitis † 1	5/2841 (0.18%)	5	3/2902 (0.10%)	3
Colitis ischaemic † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Colitis ulcerative † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Constipation † 1	395/2841 (13.90%)	485	172/2902 (5.93%)	190
Crohn's disease † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Dental caries † 1	16/2841 (0.56%)	17	5/2902 (0.17%)	7
Diarrhoea † 1	475/2841 (16.72%)	682	150/2902 (5.17%)	194
Diarrhoea haemorrhagic † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Diverticulum † 1	5/2841 (0.18%)	5	1/2902 (0.03%)	1
Diverticulum intestinal † 1	2/2841 (0.07%)	2	4/2902 (0.14%)	4
Dry mouth † 1	81/2841 (2.85%)	92	46/2902 (1.59%)	49
Duodenitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Dyschezia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Dyspepsia † 1	137/2841 (4.82%)	162	64/2902 (2.21%)	67
Dysphagia † 1	28/2841 (0.99%)	34	15/2902 (0.52%)	16
Enteritis † 1	3/2841 (0.11%)	4	0/2902 (0.00%)	0
Enterocolitis † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	3
Epigastric discomfort † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Epiploic appendagitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Erosive oesophagitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Eructation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Faeces discoloured † 1	4/2841 (0.14%)	4	0/2902 (0.00%)	0
Faeces hard † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Faeces soft † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Flatulence † 1	27/2841 (0.95%)	31	14/2902 (0.48%)	15
Food poisoning † 1	3/2841 (0.11%)	4	1/2902 (0.03%)	1
Frequent bowel movements † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gastric disorder † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Gastric polyps † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Gastric ulcer † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Gastritis † 1	29/2841 (1.02%)	32	9/2902 (0.31%)	9
Gastritis erosive † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Gastrointestinal disorder † 1	6/2841 (0.21%)	7	3/2902 (0.10%)	3
Gastrointestinal haemorrhage † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gastrointestinal inflammation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gastrointestinal pain † 1	6/2841 (0.21%)	7	3/2902 (0.10%)	3
Gastrointestinal sounds abnormal † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gastrointestinal wall thickening † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gastrooesophageal reflux disease † 1	90/2841 (3.17%)	106	55/2902 (1.90%)	59
Gingival bleeding † 1	10/2841 (0.35%)	12	1/2902 (0.03%)	1
Gingival discomfort † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Gingival oedema † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gingival pain † 1	11/2841 (0.39%)	15	3/2902 (0.10%)	3
Gingival recession † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Gingival swelling † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Glossitis † 1	3/2841 (0.11%)	4	2/2902 (0.07%)	2
Glossodynia † 1	6/2841 (0.21%)	6	1/2902 (0.03%)	1
Haematemesis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Haematochezia † 1	10/2841 (0.35%)	11	3/2902 (0.10%)	3
Haemorrhoidal haemorrhage † 1	7/2841 (0.25%)	9	7/2902 (0.24%)	12
Haemorrhoids † 1	43/2841 (1.51%)	44	25/2902 (0.86%)	26
Hiatus hernia † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	2
Hyperaesthesia teeth † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Hypertrophic anal papilla † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hypoaesthesia oral † 1	3/2841 (0.11%)	4	1/2902 (0.03%)	1
Ileus † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Impaired gastric emptying † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Inguinal hernia † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Intestinal obstruction † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Intestinal polyp † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Intra-abdominal haematoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Intussusception † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Irritable bowel syndrome † 1	2/2841 (0.07%)	2	4/2902 (0.14%)	4
Large intestinal ulcer † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Large intestine polyp † 1	4/2841 (0.14%)	4	4/2902 (0.14%)	5
Lip blister † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lip discolouration † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lip disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lip dry † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Lip erythema † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lip pain † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Lip pruritus † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lip swelling † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Lip ulceration † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Loose tooth † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lower gastrointestinal haemorrhage † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Melaena † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mouth haemorrhage † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mouth ulceration † 1	51/2841 (1.80%)	67	6/2902 (0.21%)	6
Nausea † 1	552/2841 (19.43%)	735	241/2902 (8.30%)	294
Noninfective gingivitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Noninfective sialoadenitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Odynophagia † 1	13/2841 (0.46%)	14	4/2902 (0.14%)	5
Oedematous pancreatitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oesophageal achalasia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Oesophageal discomfort † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oesophageal disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oesophageal pain † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oesophageal spasm † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oesophageal ulcer † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oesophagitis † 1	6/2841 (0.21%)	8	3/2902 (0.10%)	3
Oral discomfort † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oral disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oral dysaesthesia † 1	5/2841 (0.18%)	5	0/2902 (0.00%)	0
Oral mucosal blistering † 1	1/2841 (0.04%)	3	0/2902 (0.00%)	0
Oral pain † 1	49/2841 (1.72%)	61	6/2902 (0.21%)	6
Pancreatitis † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Paraesthesia oral † 1	4/2841 (0.14%)	5	0/2902 (0.00%)	0
Peptic ulcer † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Periodontal disease † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Proctalgia † 1	6/2841 (0.21%)	6	1/2902 (0.03%)	1
Proctitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Ranula † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Rectal haemorrhage † 1	20/2841 (0.70%)	21	12/2902 (0.41%)	13
Rectal lesion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Rectal polyp † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Rectal tenesmus † 1	1/2841 (0.04%)	2	2/2902 (0.07%)	2
Rectal ulcer † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Reflux gastritis † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Salivary duct inflammation † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Salivary gland calculus † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Salivary hypersecretion † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Small intestinal obstruction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Stomatitis † 1	280/2841 (9.86%)	428	21/2902 (0.72%)	23
Swollen tongue † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Teeth brittle † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Tongue coated † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Tongue geographic † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Tongue ulceration † 1	7/2841 (0.25%)	7	0/2902 (0.00%)	0
Tooth disorder † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Tooth loss † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Toothache † 1	35/2841 (1.23%)	39	17/2902 (0.59%)	18
Umbilical hernia † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Volvulus † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vomiting † 1	219/2841 (7.71%)	278	91/2902 (3.14%)	120
General disorders
Acute phase reaction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Adverse drug reaction † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Application site coldness † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Asthenia † 1	274/2841 (9.64%)	468	153/2902 (5.27%)	193
Axillary pain † 1	43/2841 (1.51%)	44	48/2902 (1.65%)	55
Capsular contracture associated with breast implant † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Capsular contracture associated with implant † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Catheter site inflammation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Catheter site pain † 1	0/2841 (0.00%)	0	6/2902 (0.21%)	7
Catheter site pruritus † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Catheter site scab † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Catheter site thrombosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Chest discomfort † 1	37/2841 (1.30%)	42	22/2902 (0.76%)	24
Chest pain † 1	56/2841 (1.97%)	64	51/2902 (1.76%)	54
Chills † 1	70/2841 (2.46%)	78	17/2902 (0.59%)	17
Complication associated with device † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cyst † 1	7/2841 (0.25%)	7	7/2902 (0.24%)	7
Decreased activity † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Discomfort † 1	7/2841 (0.25%)	7	7/2902 (0.24%)	7
Early satiety † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Exercise tolerance decreased † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Face oedema † 1	5/2841 (0.18%)	5	4/2902 (0.14%)	4
Facial pain † 1	4/2841 (0.14%)	4	4/2902 (0.14%)	4
Fat necrosis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Fatigue † 1	1163/2841 (40.94%)	1869	560/2902 (19.30%)	714
Feeling abnormal † 1	3/2841 (0.11%)	3	3/2902 (0.10%)	3
Feeling cold † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Feeling hot † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Feeling jittery † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Fibrosis † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Gait disturbance † 1	6/2841 (0.21%)	6	6/2902 (0.21%)	6
General physical health deterioration † 1	6/2841 (0.21%)	7	2/2902 (0.07%)	2
Granuloma † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Hernia pain † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Hyperthermia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hypertrophy † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Hypothermia † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Illness † 1	4/2841 (0.14%)	5	2/2902 (0.07%)	2
Impaired healing † 1	14/2841 (0.49%)	14	5/2902 (0.17%)	6
Implant site pain † 1	1/2841 (0.04%)	2	3/2902 (0.10%)	3
Induration † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Inflammation † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Influenza like illness † 1	166/2841 (5.84%)	205	90/2902 (3.10%)	108
Injection site pain † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Injection site phlebitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Injection site reaction † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Localised oedema † 1	16/2841 (0.56%)	16	10/2902 (0.34%)	11
Malaise † 1	32/2841 (1.13%)	34	11/2902 (0.38%)	16
Mass † 1	5/2841 (0.18%)	5	3/2902 (0.10%)	3
Mucosal disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mucosal dryness † 1	11/2841 (0.39%)	12	14/2902 (0.48%)	15
Mucosal haemorrhage † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mucosal inflammation † 1	206/2841 (7.25%)	362	10/2902 (0.34%)	10
Mucosal pain † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mucosal toxicity † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Necrosis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Nodule † 1	4/2841 (0.14%)	6	5/2902 (0.17%)	6
Non-cardiac chest pain † 1	24/2841 (0.84%)	29	29/2902 (1.00%)	33
Oedema † 1	27/2841 (0.95%)	35	25/2902 (0.86%)	29
Oedema peripheral † 1	178/2841 (6.27%)	218	121/2902 (4.17%)	137
Pain † 1	107/2841 (3.77%)	122	94/2902 (3.24%)	102
Pelvic mass † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Peripheral swelling † 1	55/2841 (1.94%)	61	33/2902 (1.14%)	36
Polyp † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	2
Pyrexia † 1	205/2841 (7.22%)	251	83/2902 (2.86%)	92
Sensitivity to weather change † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Suprapubic pain † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Swelling † 1	13/2841 (0.46%)	17	9/2902 (0.31%)	10
Swelling face † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Temperature intolerance † 1	6/2841 (0.21%)	6	1/2902 (0.03%)	1
Temperature regulation disorder † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Tenderness † 1	10/2841 (0.35%)	10	3/2902 (0.10%)	3
Thirst † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Unevaluable event † 1	9/2841 (0.32%)	9	4/2902 (0.14%)	4
Vessel puncture site pain † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Xerosis † 1	6/2841 (0.21%)	7	2/2902 (0.07%)	2
Hepatobiliary disorders
Biliary colic † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Cholecystitis † 1	8/2841 (0.28%)	8	4/2902 (0.14%)	4
Cholecystitis chronic † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cholelithiasis † 1	7/2841 (0.25%)	7	8/2902 (0.28%)	9
Gallbladder polyp † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Hepatic cyst † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Hepatic lesion † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hepatic pain † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Hepatic steatosis † 1	9/2841 (0.32%)	9	9/2902 (0.31%)	9
Hepatitis toxic † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hepatocellular injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hepatomegaly † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hepatotoxicity † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hyperbilirubinaemia † 1	2/2841 (0.07%)	3	5/2902 (0.17%)	12
Hypertransaminasaemia † 1	2/2841 (0.07%)	3	0/2902 (0.00%)	0
Jaundice † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Liver disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Liver tenderness † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Porcelain gallbladder † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Steatohepatitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Immune system disorders
Allergy to arthropod bite † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Allergy to vaccine † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Anaphylactic reaction † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Anaphylactic shock † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Drug hypersensitivity † 1	5/2841 (0.18%)	6	2/2902 (0.07%)	2
Food allergy † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hypersensitivity † 1	16/2841 (0.56%)	18	4/2902 (0.14%)	4
Immune system disorder † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	3
Mite allergy † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Multiple allergies † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Perfume sensitivity † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Sarcoidosis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Seasonal allergy † 1	19/2841 (0.67%)	20	10/2902 (0.34%)	11
Infections and infestations
Abdominal infection † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Abscess † 1	3/2841 (0.11%)	4	2/2902 (0.07%)	2
Abscess limb † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Abscess neck † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Abscess oral † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Acarodermatitis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Acute sinusitis † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	4
Anal abscess † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Appendicitis † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Arthritis infective † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Babesiosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Bacterial infection † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bacterial vaginosis † 1	2/2841 (0.07%)	2	4/2902 (0.14%)	4
Bacterial vulvovaginitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bacteriuria † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bartholin's abscess † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Beta haemolytic streptococcal infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Blastocystis infection † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Blister infected † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Breast abscess † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Breast cellulitis † 1	17/2841 (0.60%)	22	15/2902 (0.52%)	15
Bronchitis † 1	68/2841 (2.39%)	85	56/2902 (1.93%)	60
Bronchitis bacterial † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Bronchitis viral † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
COVID-19 † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Candida infection † 1	15/2841 (0.53%)	18	6/2902 (0.21%)	6
Catheter site pustule † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cellulitis † 1	53/2841 (1.87%)	66	31/2902 (1.07%)	38
Cervicitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cervicitis human papilloma virus † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Chest wall abscess † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Chronic hepatitis C † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Chronic sinusitis † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Clostridium difficile colitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Clostridium difficile infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Conjunctivitis † 1	36/2841 (1.27%)	37	27/2902 (0.93%)	28
Conjunctivitis bacterial † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Conjunctivitis viral † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cystitis † 1	30/2841 (1.06%)	34	29/2902 (1.00%)	33
Dacryocystitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Demodicidosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Dengue fever † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Dermatophytosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Device related infection † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	4
Diverticulitis † 1	7/2841 (0.25%)	8	2/2902 (0.07%)	2
Ear infection † 1	20/2841 (0.70%)	23	10/2902 (0.34%)	11
Ear infection fungal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Endometritis † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Enteritis infectious † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Enterocolitis infectious † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Epstein-Barr virus infection † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Erysipelas † 1	9/2841 (0.32%)	11	3/2902 (0.10%)	3
Erythema migrans † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Eye infection † 1	17/2841 (0.60%)	20	7/2902 (0.24%)	8
Eyelid infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Febrile infection † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Folliculitis † 1	10/2841 (0.35%)	12	9/2902 (0.31%)	9
Fungal infection † 1	16/2841 (0.56%)	18	9/2902 (0.31%)	9
Fungal skin infection † 1	6/2841 (0.21%)	6	6/2902 (0.21%)	7
Furuncle † 1	3/2841 (0.11%)	5	0/2902 (0.00%)	0
Gastroenteritis † 1	46/2841 (1.62%)	51	20/2902 (0.69%)	21
Gastroenteritis norovirus † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Gastroenteritis salmonella † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Gastroenteritis viral † 1	18/2841 (0.63%)	19	10/2902 (0.34%)	10
Gastrointestinal bacterial overgrowth † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Gastrointestinal infection † 1	5/2841 (0.18%)	5	4/2902 (0.14%)	4
Gastrointestinal viral infection † 1	4/2841 (0.14%)	4	0/2902 (0.00%)	0
Genital herpes † 1	3/2841 (0.11%)	4	3/2902 (0.10%)	3
Genital herpes simplex † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gingival abscess † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Gingivitis † 1	6/2841 (0.21%)	7	9/2902 (0.31%)	9
Haemophilus infection † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Haemorrhoid infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hand-foot-and-mouth disease † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Helicobacter gastritis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Helicobacter infection † 1	6/2841 (0.21%)	6	4/2902 (0.14%)	4
Herpes ophthalmic † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Herpes simplex † 1	12/2841 (0.42%)	13	4/2902 (0.14%)	4
Herpes simplex reactivation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Herpes virus infection † 1	9/2841 (0.32%)	10	3/2902 (0.10%)	6
Herpes zoster † 1	52/2841 (1.83%)	57	50/2902 (1.72%)	53
Hordeolum † 1	6/2841 (0.21%)	6	8/2902 (0.28%)	8
Incision site cellulitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Infected bite † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Infected cyst † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Infected dermal cyst † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Infected seroma † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	4
Infected skin ulcer † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Infection † 1	17/2841 (0.60%)	18	10/2902 (0.34%)	11
Infection parasitic † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Infective tenosynovitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Influenza † 1	102/2841 (3.59%)	109	45/2902 (1.55%)	48
Kidney infection † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Labyrinthitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Laryngitis † 1	21/2841 (0.74%)	22	5/2902 (0.17%)	5
Laryngitis viral † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lip infection † 1	8/2841 (0.28%)	8	3/2902 (0.10%)	3
Localised infection † 1	7/2841 (0.25%)	8	4/2902 (0.14%)	4
Lower respiratory tract infection † 1	36/2841 (1.27%)	49	20/2902 (0.69%)	21
Lower respiratory tract infection viral † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lyme disease † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	2
Lymph gland infection † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Lymphangitis † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	3
Mastitis † 1	29/2841 (1.02%)	43	43/2902 (1.48%)	47
Mucosal infection † 1	6/2841 (0.21%)	8	3/2902 (0.10%)	3
Nail infection † 1	5/2841 (0.18%)	5	5/2902 (0.17%)	7
Nasal abscess † 1	3/2841 (0.11%)	4	0/2902 (0.00%)	0
Nasal herpes † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Nasopharyngitis † 1	210/2841 (7.39%)	275	127/2902 (4.38%)	157
Nipple infection † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Oesophageal candidiasis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oesophageal infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Onychomycosis † 1	8/2841 (0.28%)	9	7/2902 (0.24%)	7
Oral candidiasis † 1	12/2841 (0.42%)	13	4/2902 (0.14%)	4
Oral fungal infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oral herpes † 1	65/2841 (2.29%)	88	16/2902 (0.55%)	17
Oral infection † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	2
Otitis externa † 1	6/2841 (0.21%)	6	3/2902 (0.10%)	3
Otitis media † 1	19/2841 (0.67%)	22	5/2902 (0.17%)	5
Papilloma viral infection † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Parainfluenzae virus infection † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Parasitic gastroenteritis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Paronychia † 1	9/2841 (0.32%)	9	8/2902 (0.28%)	8
Parotitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pelvic inflammatory disease † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pericoronitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Perineal abscess † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Periodontitis † 1	3/2841 (0.11%)	4	1/2902 (0.03%)	1
Periorbital cellulitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Periorbital infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Peripheral nerve infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Periumbilical abscess † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pertussis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pharyngitis † 1	50/2841 (1.76%)	63	19/2902 (0.65%)	20
Pharyngitis streptococcal † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Pilonidal cyst † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Pneumonia † 1	38/2841 (1.34%)	42	35/2902 (1.21%)	37
Pneumonia influenzal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Post procedural cellulitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Post procedural infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Postoperative wound infection † 1	8/2841 (0.28%)	8	3/2902 (0.10%)	3
Psoas abscess † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pulpitis dental † 1	2/2841 (0.07%)	3	2/2902 (0.07%)	2
Pustule † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Pyelonephritis † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Rash pustular † 1	12/2841 (0.42%)	13	4/2902 (0.14%)	5
Respiratory tract infection † 1	52/2841 (1.83%)	73	31/2902 (1.07%)	35
Respiratory tract infection viral † 1	3/2841 (0.11%)	4	3/2902 (0.10%)	3
Rhinitis † 1	36/2841 (1.27%)	46	12/2902 (0.41%)	13
Sialoadenitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Sinobronchitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Sinusitis † 1	105/2841 (3.70%)	132	61/2902 (2.10%)	74
Skin candida † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Skin infection † 1	63/2841 (2.22%)	85	29/2902 (1.00%)	31
Soft tissue infection † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Sputum purulent † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Staphylococcal infection † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	3
Streptococcal infection † 1	1/2841 (0.04%)	3	0/2902 (0.00%)	0
Subcutaneous abscess † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Suspected COVID-19 † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Tinea infection † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Tinea pedis † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Tinea versicolour † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Tonsillitis † 1	9/2841 (0.32%)	10	10/2902 (0.34%)	10
Tooth abscess † 1	14/2841 (0.49%)	16	7/2902 (0.24%)	8
Tooth infection † 1	26/2841 (0.92%)	30	21/2902 (0.72%)	21
Toxoplasmosis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Tracheitis † 1	7/2841 (0.25%)	8	0/2902 (0.00%)	0
Tuberculosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Upper respiratory tract infection † 1	304/2841 (10.70%)	390	185/2902 (6.37%)	229
Urethritis † 1	1/2841 (0.04%)	2	1/2902 (0.03%)	2
Urinary tract infection † 1	234/2841 (8.24%)	320	145/2902 (5.00%)	204
Urinary tract infection viral † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Vaginal infection † 1	27/2841 (0.95%)	28	18/2902 (0.62%)	21
Varicella † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vascular device infection † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Vestibulitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Viral infection † 1	28/2841 (0.99%)	30	18/2902 (0.62%)	18
Viral skin infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Viral upper respiratory tract infection † 1	7/2841 (0.25%)	7	5/2902 (0.17%)	6
Vulval cellulitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vulvitis † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Vulvovaginal candidiasis † 1	15/2841 (0.53%)	17	3/2902 (0.10%)	3
Vulvovaginal human papilloma virus infection † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vulvovaginal mycotic infection † 1	8/2841 (0.28%)	8	12/2902 (0.41%)	13
Wound infection † 1	14/2841 (0.49%)	16	7/2902 (0.24%)	8
Injury, poisoning and procedural complications
Abdominal wound dehiscence † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Animal bite † 1	4/2841 (0.14%)	4	3/2902 (0.10%)	3
Ankle fracture † 1	10/2841 (0.35%)	11	13/2902 (0.45%)	13
Arthropod bite † 1	22/2841 (0.77%)	24	11/2902 (0.38%)	11
Arthropod sting † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Axillary web syndrome † 1	14/2841 (0.49%)	15	5/2902 (0.17%)	5
Back injury † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Bite † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Bone contusion † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Breast injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Breast procedural complication † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Chest injury † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Chillblains † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Clavicle fracture † 1	0/2841 (0.00%)	0	4/2902 (0.14%)	6
Compression fracture † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Concussion † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Contusion † 1	95/2841 (3.34%)	108	37/2902 (1.27%)	43
Corneal abrasion † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Craniocerebral injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Epicondylitis † 1	5/2841 (0.18%)	6	3/2902 (0.10%)	3
Exposure to toxic agent † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Eye contusion † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Eye injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Face injury † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Fall † 1	57/2841 (2.01%)	68	40/2902 (1.38%)	49
Fibula fracture † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Foot fracture † 1	10/2841 (0.35%)	10	16/2902 (0.55%)	17
Forearm fracture † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Fracture † 1	3/2841 (0.11%)	3	3/2902 (0.10%)	3
Fractured coccyx † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Fractured sacrum † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Gastroparesis postoperative † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hair injury † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hand fracture † 1	1/2841 (0.04%)	2	4/2902 (0.14%)	4
Head injury † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Heat stroke † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Humerus fracture † 1	3/2841 (0.11%)	3	5/2902 (0.17%)	5
Iliotibial band syndrome † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Incision site complication † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Incision site erythema † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Incision site fibrosis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Incision site pain † 1	18/2841 (0.63%)	21	17/2902 (0.59%)	19
Incision site pruritus † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Infusion related reaction † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Injury † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Joint dislocation † 1	2/2841 (0.07%)	3	2/2902 (0.07%)	2
Joint injury † 1	3/2841 (0.11%)	3	3/2902 (0.10%)	3
Ligament injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ligament rupture † 1	2/2841 (0.07%)	2	5/2902 (0.17%)	6
Ligament sprain † 1	12/2841 (0.42%)	12	10/2902 (0.34%)	10
Limb injury † 1	8/2841 (0.28%)	8	4/2902 (0.14%)	4
Lip injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lower limb fracture † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Lumbar vertebral fracture † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Median nerve injury † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Meniscus injury † 1	5/2841 (0.18%)	6	7/2902 (0.24%)	7
Mouth injury † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mucosal excoriation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Muscle injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Muscle rupture † 1	1/2841 (0.04%)	2	3/2902 (0.10%)	3
Muscle strain † 1	6/2841 (0.21%)	6	4/2902 (0.14%)	4
Musculoskeletal injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Musculoskeletal procedural complication † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nail injury † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Nerve injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Patella fracture † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Post procedural complication † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Post procedural constipation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Post procedural contusion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Post procedural discomfort † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Post procedural haematoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Post procedural haemorrhage † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Post procedural inflammation † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Post procedural oedema † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Post procedural swelling † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Post-traumatic neck syndrome † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Post-traumatic pain † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	4
Postpericardiotomy syndrome † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Procedural complication † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Procedural nausea † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Procedural pain † 1	48/2841 (1.69%)	58	45/2902 (1.55%)	55
Procedural site reaction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Procedural vomiting † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pulmonary radiation injury † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Radiation associated pain † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Radiation fibrosis † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Radiation fibrosis - lung † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Radiation injury † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Radiation neuropathy † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Radiation pneumonitis † 1	6/2841 (0.21%)	6	6/2902 (0.21%)	7
Radiation skin injury † 1	12/2841 (0.42%)	15	20/2902 (0.69%)	20
Radius fracture † 1	7/2841 (0.25%)	7	6/2902 (0.21%)	6
Rectal injury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Rib fracture † 1	10/2841 (0.35%)	10	12/2902 (0.41%)	13
Road traffic accident † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Scar † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Seroma † 1	24/2841 (0.84%)	28	36/2902 (1.24%)	46
Skin abrasion † 1	2/2841 (0.07%)	2	4/2902 (0.14%)	4
Skin flap necrosis † 1	1/2841 (0.04%)	3	1/2902 (0.03%)	1
Skin laceration † 1	4/2841 (0.14%)	4	4/2902 (0.14%)	4
Spinal compression fracture † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Spinal fracture † 1	0/2841 (0.00%)	0	5/2902 (0.17%)	8
Sternal fracture † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Stress fracture † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Subdural haematoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Sunburn † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Suture related complication † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Synovial rupture † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Tendon injury † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Tendon rupture † 1	0/2841 (0.00%)	0	5/2902 (0.17%)	5
Thermal burn † 1	6/2841 (0.21%)	6	8/2902 (0.28%)	10
Thoracic vertebral fracture † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Tibia fracture † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Tooth fracture † 1	9/2841 (0.32%)	9	3/2902 (0.10%)	4
Traumatic fracture † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ulna fracture † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Upper limb fracture † 1	7/2841 (0.25%)	7	5/2902 (0.17%)	7
Vascular access site thrombosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Wound † 1	12/2841 (0.42%)	12	4/2902 (0.14%)	5
Wound complication † 1	19/2841 (0.67%)	21	3/2902 (0.10%)	3
Wound decomposition † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Wound dehiscence † 1	16/2841 (0.56%)	19	7/2902 (0.24%)	7
Wound secretion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Wrist fracture † 1	9/2841 (0.32%)	9	10/2902 (0.34%)	10
Investigations
AST/ALT ratio abnormal † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Activated partial thromboplastin time prolonged † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Alanine aminotransferase † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Alanine aminotransferase decreased † 1	5/2841 (0.18%)	6	4/2902 (0.14%)	4
Alanine aminotransferase increased † 1	212/2841 (7.46%)	345	138/2902 (4.76%)	175
Albumin globulin ratio decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Amylase increased † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Anion gap decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Anion gap increased † 1	5/2841 (0.18%)	6	1/2902 (0.03%)	1
Antimitochondrial antibody positive † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Antinuclear antibody increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Aspartate aminotransferase † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Aspartate aminotransferase decreased † 1	6/2841 (0.21%)	6	2/2902 (0.07%)	2
Aspartate aminotransferase increased † 1	210/2841 (7.39%)	288	114/2902 (3.93%)	151
Bacterial test † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Basophil count increased † 1	5/2841 (0.18%)	7	0/2902 (0.00%)	0
Bilirubin conjugated decreased † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	5
Biopsy skin † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Blood 1,25-dihydroxycholecalciferol decreased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Blood albumin decreased † 1	5/2841 (0.18%)	6	8/2902 (0.28%)	9
Blood albumin increased † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Blood alkaline phosphatase † 1	5/2841 (0.18%)	7	2/2902 (0.07%)	2
Blood alkaline phosphatase decreased † 1	6/2841 (0.21%)	8	4/2902 (0.14%)	4
Blood alkaline phosphatase increased † 1	75/2841 (2.64%)	91	98/2902 (3.38%)	127
Blood bicarbonate increased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Blood bilirubin † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Blood bilirubin abnormal † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Blood bilirubin decreased † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Blood bilirubin increased † 1	29/2841 (1.02%)	47	28/2902 (0.96%)	41
Blood calcium decreased † 1	6/2841 (0.21%)	8	2/2902 (0.07%)	3
Blood calcium increased † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	4
Blood chloride decreased † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	5
Blood chloride increased † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	2
Blood cholesterol increased † 1	21/2841 (0.74%)	22	47/2902 (1.62%)	51
Blood creatine increased † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Blood creatine phosphokinase increased † 1	4/2841 (0.14%)	4	0/2902 (0.00%)	0
Blood creatinine decreased † 1	5/2841 (0.18%)	5	3/2902 (0.10%)	4
Blood creatinine increased † 1	91/2841 (3.20%)	133	50/2902 (1.72%)	80
Blood culture positive † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Blood folate decreased † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Blood glucose decreased † 1	2/2841 (0.07%)	4	2/2902 (0.07%)	2
Blood glucose increased † 1	17/2841 (0.60%)	24	25/2902 (0.86%)	30
Blood iron decreased † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Blood ketone body † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Blood lactate dehydrogenase increased † 1	8/2841 (0.28%)	8	0/2902 (0.00%)	0
Blood magnesium decreased † 1	3/2841 (0.11%)	3	4/2902 (0.14%)	4
Blood phosphorus decreased † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Blood phosphorus increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Blood potassium decreased † 1	8/2841 (0.28%)	9	1/2902 (0.03%)	1
Blood potassium increased † 1	2/2841 (0.07%)	4	2/2902 (0.07%)	2
Blood pressure diastolic increased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Blood pressure increased † 1	3/2841 (0.11%)	3	5/2902 (0.17%)	8
Blood pressure systolic increased † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Blood sodium decreased † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	4
Blood sodium increased † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Blood testosterone decreased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Blood thyroid stimulating hormone decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Blood thyroid stimulating hormone increased † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Blood triglycerides increased † 1	6/2841 (0.21%)	6	7/2902 (0.24%)	10
Blood urea decreased † 1	2/2841 (0.07%)	3	2/2902 (0.07%)	3
Blood urea increased † 1	11/2841 (0.39%)	15	8/2902 (0.28%)	11
Blood urea nitrogen/creatinine ratio † 1	2/2841 (0.07%)	4	0/2902 (0.00%)	0
Blood uric acid increased † 1	0/2841 (0.00%)	0	6/2902 (0.21%)	6
Blood urine present † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Body temperature increased † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Bone density decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Brain natriuretic peptide increased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
C-reactive protein increased † 1	4/2841 (0.14%)	4	0/2902 (0.00%)	0
Carbon dioxide abnormal † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Carbon dioxide decreased † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Carbon dioxide increased † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Cardiac murmur † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	2
Carotid bruit † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Coagulation time prolonged † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Colonoscopy abnormal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ejection fraction decreased † 1	4/2841 (0.14%)	5	3/2902 (0.10%)	3
Electrocardiogram QT prolonged † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Eosinophil count increased † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	3
Eosinophil percentage decreased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Eosinophil percentage increased † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Fibrin D dimer increased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Gamma-glutamyltransferase † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gamma-glutamyltransferase increased † 1	18/2841 (0.63%)	35	21/2902 (0.72%)	35
Glomerular filtration rate decreased † 1	6/2841 (0.21%)	11	1/2902 (0.03%)	1
Glomerular filtration rate increased † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Glycosylated haemoglobin decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Glycosylated haemoglobin increased † 1	15/2841 (0.53%)	18	20/2902 (0.69%)	22
Granulocyte count decreased † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Granulocyte count increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Haematocrit decreased † 1	28/2841 (0.99%)	41	6/2902 (0.21%)	7
Haemoglobin decreased † 1	42/2841 (1.48%)	79	12/2902 (0.41%)	15
Haemoglobin increased † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Heart rate decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Heart rate increased † 1	4/2841 (0.14%)	6	2/2902 (0.07%)	3
Heart rate irregular † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hepatic enzyme increased † 1	7/2841 (0.25%)	9	5/2902 (0.17%)	5
High density lipoprotein decreased † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Influenza A virus test positive † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
International normalised ratio increased † 1	1/2841 (0.04%)	2	2/2902 (0.07%)	5
Intestinal transit time abnormal † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Intraocular pressure increased † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Liver function test abnormal † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Liver function test increased † 1	4/2841 (0.14%)	4	8/2902 (0.28%)	8
Low density lipoprotein increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lymph node palpable † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lymphocyte count † 1	1/2841 (0.04%)	2	1/2902 (0.03%)	1
Lymphocyte count decreased † 1	317/2841 (11.16%)	926	100/2902 (3.45%)	161
Lymphocyte count increased † 1	7/2841 (0.25%)	7	1/2902 (0.03%)	2
Lymphocyte percentage increased † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Mean cell haemoglobin concentration † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Mean cell haemoglobin concentration abnormal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Mean cell haemoglobin concentration decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mean cell haemoglobin concentration increased † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Mean cell haemoglobin decreased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Mean cell haemoglobin increased † 1	11/2841 (0.39%)	14	1/2902 (0.03%)	1
Mean cell volume † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mean cell volume abnormal † 1	8/2841 (0.28%)	8	0/2902 (0.00%)	0
Mean cell volume decreased † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Mean cell volume increased † 1	14/2841 (0.49%)	17	1/2902 (0.03%)	1
Mean platelet volume decreased † 1	5/2841 (0.18%)	6	2/2902 (0.07%)	3
Mean platelet volume increased † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Monocyte count decreased † 1	13/2841 (0.46%)	24	1/2902 (0.03%)	1
Monocyte count increased † 1	8/2841 (0.28%)	9	1/2902 (0.03%)	1
Monocyte percentage decreased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Neutrophil count † 1	9/2841 (0.32%)	13	0/2902 (0.00%)	0
Neutrophil count abnormal † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Neutrophil count decreased † 1	1344/2841 (47.31%)	6144	67/2902 (2.31%)	109
Neutrophil count increased † 1	4/2841 (0.14%)	5	6/2902 (0.21%)	6
Neutrophil percentage decreased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Non-high-density lipoprotein cholesterol increased † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Occult blood positive † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Pancreatic enzymes decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Physical examination abnormal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Platelet count decreased † 1	436/2841 (15.35%)	850	35/2902 (1.21%)	50
Platelet count increased † 1	7/2841 (0.25%)	7	2/2902 (0.07%)	2
Prostatic specific antigen increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Protein total abnormal † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Protein total decreased † 1	5/2841 (0.18%)	5	8/2902 (0.28%)	10
Protein total increased † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Red blood cell count decreased † 1	35/2841 (1.23%)	49	7/2902 (0.24%)	7
Red blood cell count increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Red blood cell sedimentation rate increased † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Red cell distribution width decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Red cell distribution width increased † 1	13/2841 (0.46%)	14	1/2902 (0.03%)	1
Rheumatoid factor increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Smear cervix abnormal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Specific gravity urine increased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Transaminases increased † 1	7/2841 (0.25%)	8	7/2902 (0.24%)	7
Troponin I increased † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Urine analysis abnormal † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Urine leukocyte esterase † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vitamin B12 decreased † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Vitamin D decreased † 1	9/2841 (0.32%)	9	13/2902 (0.45%)	13
Weight decreased † 1	44/2841 (1.55%)	48	29/2902 (1.00%)	40
Weight increased † 1	116/2841 (4.08%)	155	136/2902 (4.69%)	162
White blood cell count † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
White blood cell count decreased † 1	1187/2841 (41.78%)	5122	155/2902 (5.34%)	242
White blood cell count increased † 1	1/2841 (0.04%)	1	4/2902 (0.14%)	4
White blood cells urine † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Metabolism and nutrition disorders
Abnormal loss of weight † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Appetite disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Decreased appetite † 1	151/2841 (5.32%)	176	73/2902 (2.52%)	87
Dehydration † 1	17/2841 (0.60%)	18	5/2902 (0.17%)	5
Diabetes mellitus † 1	3/2841 (0.11%)	3	6/2902 (0.21%)	6
Diabetes mellitus inadequate control † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Dyslipidaemia † 1	2/2841 (0.07%)	2	8/2902 (0.28%)	9
Fluid retention † 1	5/2841 (0.18%)	5	10/2902 (0.34%)	11
Folate deficiency † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Food craving † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Glucose tolerance impaired † 1	3/2841 (0.11%)	3	6/2902 (0.21%)	7
Gout † 1	5/2841 (0.18%)	6	4/2902 (0.14%)	4
Hyperalbuminaemia † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Hypercalcaemia † 1	45/2841 (1.58%)	59	44/2902 (1.52%)	61
Hyperchloraemia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hypercholesterolaemia † 1	8/2841 (0.28%)	8	23/2902 (0.79%)	30
Hyperglycaemia † 1	119/2841 (4.19%)	185	95/2902 (3.27%)	141
Hyperkalaemia † 1	29/2841 (1.02%)	36	35/2902 (1.21%)	35
Hyperlipidaemia † 1	6/2841 (0.21%)	6	9/2902 (0.31%)	9
Hypermagnesaemia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hypernatraemia † 1	29/2841 (1.02%)	32	35/2902 (1.21%)	39
Hyperphagia † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Hyperphosphataemia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hypertriglyceridaemia † 1	13/2841 (0.46%)	15	14/2902 (0.48%)	17
Hyperuricaemia † 1	5/2841 (0.18%)	6	10/2902 (0.34%)	14
Hypoalbuminaemia † 1	43/2841 (1.51%)	63	28/2902 (0.96%)	40
Hypocalcaemia † 1	47/2841 (1.65%)	69	30/2902 (1.03%)	35
Hypochloraemia † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Hypoglycaemia † 1	24/2841 (0.84%)	24	17/2902 (0.59%)	18
Hypokalaemia † 1	93/2841 (3.27%)	140	53/2902 (1.83%)	69
Hypomagnesaemia † 1	22/2841 (0.77%)	23	8/2902 (0.28%)	10
Hyponatraemia † 1	50/2841 (1.76%)	57	36/2902 (1.24%)	46
Hypophosphataemia † 1	15/2841 (0.53%)	20	7/2902 (0.24%)	9
Hypoproteinaemia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hypovitaminosis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Increased appetite † 1	3/2841 (0.11%)	3	6/2902 (0.21%)	6
Iron deficiency † 1	1/2841 (0.04%)	2	3/2902 (0.10%)	3
Lipoedema † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Metabolic alkalosis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Obesity † 1	3/2841 (0.11%)	7	0/2902 (0.00%)	0
Polydipsia † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Tetany † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Type 1 diabetes mellitus † 1	1/2841 (0.04%)	4	0/2902 (0.00%)	0
Type 2 diabetes mellitus † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Vitamin B complex deficiency † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vitamin B12 deficiency † 1	6/2841 (0.21%)	6	2/2902 (0.07%)	2
Vitamin D deficiency † 1	29/2841 (1.02%)	29	25/2902 (0.86%)	26
Weight loss poor † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1087/2841 (38.26%)	1650	1305/2902 (44.97%)	2034
Arthritis † 1	25/2841 (0.88%)	28	33/2902 (1.14%)	41
Arthropathy † 1	1/2841 (0.04%)	2	1/2902 (0.03%)	2
Axillary mass † 1	6/2841 (0.21%)	6	4/2902 (0.14%)	4
Back pain † 1	311/2841 (10.95%)	369	287/2902 (9.89%)	346
Bone disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Bone loss † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Bone pain † 1	80/2841 (2.82%)	93	87/2902 (3.00%)	97
Bursitis † 1	13/2841 (0.46%)	13	14/2902 (0.48%)	16
Cervical spinal stenosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Chest wall haematoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Chest wall mass † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Chest wall necrosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Chondrocalcinosis pyrophosphate † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Chondromalacia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Coccydynia † 1	7/2841 (0.25%)	8	9/2902 (0.31%)	9
Costochondritis † 1	1/2841 (0.04%)	2	2/2902 (0.07%)	2
Enthesopathy † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Exostosis † 1	2/2841 (0.07%)	3	1/2902 (0.03%)	1
Fasciitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Fibromyalgia † 1	5/2841 (0.18%)	6	1/2902 (0.03%)	1
Fistula † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Flank pain † 1	23/2841 (0.81%)	25	12/2902 (0.41%)	14
Foot deformity † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Groin pain † 1	5/2841 (0.18%)	5	8/2902 (0.28%)	8
Hand deformity † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Interspinous osteoarthritis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Intervertebral disc degeneration † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Intervertebral disc disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Intervertebral disc protrusion † 1	7/2841 (0.25%)	7	8/2902 (0.28%)	8
Jaw cyst † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Joint ankylosis † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	4
Joint contracture † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Joint effusion † 1	7/2841 (0.25%)	8	1/2902 (0.03%)	1
Joint instability † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Joint noise † 1	3/2841 (0.11%)	3	4/2902 (0.14%)	4
Joint range of motion decreased † 1	33/2841 (1.16%)	36	29/2902 (1.00%)	34
Joint stiffness † 1	58/2841 (2.04%)	63	49/2902 (1.69%)	52
Joint swelling † 1	20/2841 (0.70%)	23	15/2902 (0.52%)	20
Limb discomfort † 1	8/2841 (0.28%)	10	12/2902 (0.41%)	13
Limb mass † 1	3/2841 (0.11%)	4	0/2902 (0.00%)	0
Lupus-like syndrome † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mandibular mass † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Medial tibial stress syndrome † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Mobility decreased † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Muscle contracture † 1	6/2841 (0.21%)	7	5/2902 (0.17%)	6
Muscle discomfort † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Muscle disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Muscle fatigue † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Muscle rigidity † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	3
Muscle spasms † 1	193/2841 (6.79%)	229	124/2902 (4.27%)	131
Muscle tightness † 1	3/2841 (0.11%)	4	12/2902 (0.41%)	12
Muscle twitching † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	4
Muscular weakness † 1	45/2841 (1.58%)	51	29/2902 (1.00%)	32
Musculoskeletal chest pain † 1	99/2841 (3.48%)	117	85/2902 (2.93%)	92
Musculoskeletal discomfort † 1	16/2841 (0.56%)	23	20/2902 (0.69%)	25
Musculoskeletal disorder † 1	3/2841 (0.11%)	3	6/2902 (0.21%)	6
Musculoskeletal pain † 1	65/2841 (2.29%)	93	81/2902 (2.79%)	107
Musculoskeletal stiffness † 1	40/2841 (1.41%)	47	64/2902 (2.21%)	71
Myalgia † 1	250/2841 (8.80%)	315	235/2902 (8.10%)	276
Myofascial pain syndrome † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Myositis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Neck mass † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Neck pain † 1	69/2841 (2.43%)	73	72/2902 (2.48%)	78
Nodal osteoarthritis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Osteitis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Osteoarthritis † 1	18/2841 (0.63%)	19	27/2902 (0.93%)	30
Osteochondrosis † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Osteopenia † 1	60/2841 (2.11%)	60	70/2902 (2.41%)	70
Osteoporosis † 1	75/2841 (2.64%)	75	90/2902 (3.10%)	91
Pain in extremity † 1	265/2841 (9.33%)	347	280/2902 (9.65%)	349
Pain in jaw † 1	21/2841 (0.74%)	22	12/2902 (0.41%)	14
Periarthritis † 1	7/2841 (0.25%)	7	10/2902 (0.34%)	11
Periostitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Plantar fascial fibromatosis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Plantar fasciitis † 1	16/2841 (0.56%)	17	16/2902 (0.55%)	17
Polyarthritis † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Polymyalgia rheumatica † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Pubic pain † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Rheumatic disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Rheumatoid arthritis † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Rotator cuff syndrome † 1	3/2841 (0.11%)	3	12/2902 (0.41%)	12
Scoliosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Soft tissue disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Soft tissue mass † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Soft tissue swelling † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Spinal osteoarthritis † 1	3/2841 (0.11%)	3	6/2902 (0.21%)	6
Spinal pain † 1	8/2841 (0.28%)	10	10/2902 (0.34%)	11
Spinal stenosis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Spinal synovial cyst † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Synovial cyst † 1	3/2841 (0.11%)	3	10/2902 (0.34%)	11
Synovitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Systemic scleroderma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Temporomandibular joint syndrome † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Tendon calcification † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Tendon discomfort † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Tendon disorder † 1	4/2841 (0.14%)	4	5/2902 (0.17%)	5
Tendon pain † 1	5/2841 (0.18%)	7	2/2902 (0.07%)	2
Tendon sheath disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Tendonitis † 1	28/2841 (0.99%)	32	28/2902 (0.96%)	35
Tenosynovitis † 1	1/2841 (0.04%)	1	6/2902 (0.21%)	6
Tenosynovitis stenosans † 1	9/2841 (0.32%)	13	9/2902 (0.31%)	10
Torticollis † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Trigger finger † 1	28/2841 (0.99%)	35	28/2902 (0.96%)	29
Trismus † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Wrist deformity † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acrochordon † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Adenocarcinoma of colon † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Adenoma benign † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Basal cell carcinoma † 1	6/2841 (0.21%)	6	14/2902 (0.48%)	15
Benign breast neoplasm † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Benign neoplasm † 1	3/2841 (0.11%)	3	4/2902 (0.14%)	4
Benign neoplasm of skin † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Benign neoplasm of thyroid gland † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Borderline serous tumour of ovary † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bowen's disease † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Cervix carcinoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Clear cell renal cell carcinoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Colon adenoma † 1	0/2841 (0.00%)	0	4/2902 (0.14%)	4
Colon cancer † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Colorectal adenocarcinoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Dysplastic naevus † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Fibroadenoma of breast † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Fibroma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Fibrous histiocytoma † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Haemangioma † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Haemangioma of liver † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Haemangioma of skin † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Hair follicle tumour benign † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hypergammaglobulinaemia benign monoclonal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Intraductal papillary-mucinous carcinoma of pancreas † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Keratinising squamous cell carcinoma of nasopharynx † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Leiomyoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lentigo maligna † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Leukaemia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lipoma † 1	6/2841 (0.21%)	6	6/2902 (0.21%)	8
Lipoma of breast † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lymphoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Malignant melanoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Malignant melanoma in situ † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Melanocytic naevus † 1	8/2841 (0.28%)	9	6/2902 (0.21%)	6
Meningioma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Metastases to bone † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mucinous adenocarcinoma of appendix † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Neoplasm † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Neoplasm malignant † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Neoplasm skin † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Neuroendocrine tumour † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oral fibroma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Oral neoplasm † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Ovarian cancer † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Ovarian neoplasm † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Papilloma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Parathyroid tumour benign † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pituitary tumour benign † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Prostate cancer † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Renal hamartoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Salivary gland adenoma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Sarcomatoid mesothelioma † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Seborrhoeic keratosis † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Serous cystadenocarcinoma ovary † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Skin papilloma † 1	5/2841 (0.18%)	6	3/2902 (0.10%)	3
Squamous cell carcinoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Squamous cell carcinoma of skin † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Squamous cell carcinoma of the tongue † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Tendon neoplasm † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Thyroid adenoma † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Tumour pain † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Uterine leiomyoma † 1	4/2841 (0.14%)	4	8/2902 (0.28%)	8
Vulval neoplasm † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vulvovaginal warts † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Nervous system disorders
Ageusia † 1	5/2841 (0.18%)	5	0/2902 (0.00%)	0
Akathisia † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Allodynia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Amnesia † 1	24/2841 (0.84%)	24	21/2902 (0.72%)	23
Anosmia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Aphasia † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	4
Ataxia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Auditory nerve disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Aura † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Autonomic nervous system imbalance † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Balance disorder † 1	5/2841 (0.18%)	5	4/2902 (0.14%)	4
Brachial plexopathy † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Brain oedema † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Burning sensation † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Carpal tunnel syndrome † 1	21/2841 (0.74%)	25	31/2902 (1.07%)	35
Cerebral haemorrhage † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cerebrovascular accident † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Cerebrovascular disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cervicobrachial syndrome † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Cognitive disorder † 1	34/2841 (1.20%)	41	20/2902 (0.69%)	22
Complex regional pain syndrome † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Dementia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Demyelination † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Depressed level of consciousness † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Disturbance in attention † 1	33/2841 (1.16%)	38	22/2902 (0.76%)	22
Dizziness † 1	248/2841 (8.73%)	306	169/2902 (5.82%)	190
Dizziness postural † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	2
Drooling † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Dysaesthesia † 1	14/2841 (0.49%)	15	7/2902 (0.24%)	8
Dysarthria † 1	1/2841 (0.04%)	2	1/2902 (0.03%)	1
Dysgeusia † 1	72/2841 (2.53%)	81	14/2902 (0.48%)	14
Dysgraphia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Dyskinesia † 1	2/2841 (0.07%)	2	4/2902 (0.14%)	4
Encephalopathy † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Extrapyramidal disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Facial nerve disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Facial neuralgia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Facial paralysis † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Head discomfort † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Headache † 1	445/2841 (15.66%)	590	338/2902 (11.65%)	405
Hydrocephalus † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hyperaesthesia † 1	8/2841 (0.28%)	8	3/2902 (0.10%)	3
Hypersomnia † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Hypertonia † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Hypoaesthesia † 1	30/2841 (1.06%)	38	31/2902 (1.07%)	35
Hypokinesia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hyposmia † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Intercostal neuralgia † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Intracranial aneurysm † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lethargy † 1	14/2841 (0.49%)	16	7/2902 (0.24%)	7
Memory impairment † 1	46/2841 (1.62%)	50	59/2902 (2.03%)	64
Mental impairment † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Migraine † 1	27/2841 (0.95%)	32	21/2902 (0.72%)	23
Migraine with aura † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Morton's neuralgia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Muscle contractions involuntary † 1	2/2841 (0.07%)	3	0/2902 (0.00%)	0
Muscle spasticity † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Myoclonus † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nerve compression † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	4
Nervous system disorder † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	2
Neuralgia † 1	21/2841 (0.74%)	21	15/2902 (0.52%)	15
Neuritis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Neuropathy peripheral † 1	148/2841 (5.21%)	186	102/2902 (3.51%)	121
Neurotoxicity † 1	10/2841 (0.35%)	10	11/2902 (0.38%)	11
Occipital neuralgia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Paraesthesia † 1	115/2841 (4.05%)	129	82/2902 (2.83%)	89
Paresis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Parkinson's disease † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Parosmia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Partial seizures † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Peripheral motor neuropathy † 1	8/2841 (0.28%)	11	7/2902 (0.24%)	7
Peripheral nerve lesion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Peripheral sensory neuropathy † 1	65/2841 (2.29%)	78	49/2902 (1.69%)	53
Petit mal epilepsy † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Phantom limb syndrome † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Polyneuropathy † 1	12/2841 (0.42%)	14	12/2902 (0.41%)	14
Poor quality sleep † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Post herpetic neuralgia † 1	2/2841 (0.07%)	3	1/2902 (0.03%)	1
Presyncope † 1	9/2841 (0.32%)	9	3/2902 (0.10%)	3
Radicular pain † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Resting tremor † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Restless legs syndrome † 1	7/2841 (0.25%)	7	9/2902 (0.31%)	9
Sciatica † 1	19/2841 (0.67%)	20	19/2902 (0.65%)	22
Seizure † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Sensorimotor disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Sensory disturbance † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Sinus headache † 1	6/2841 (0.21%)	7	4/2902 (0.14%)	4
Somnolence † 1	7/2841 (0.25%)	7	7/2902 (0.24%)	7
Speech disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Spinal cord herniation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Syncope † 1	23/2841 (0.81%)	23	17/2902 (0.59%)	19
Taste disorder † 1	27/2841 (0.95%)	29	4/2902 (0.14%)	4
Tension headache † 1	4/2841 (0.14%)	4	3/2902 (0.10%)	3
Thoracic outlet syndrome † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Transient ischaemic attack † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Tremor † 1	14/2841 (0.49%)	14	12/2902 (0.41%)	13
Trigeminal neuralgia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Visual field defect † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Product Issues
Device failure † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Device leakage † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Psychiatric disorders
Agitation Mood Disturbance † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Abnormal dreams † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Adjustment disorder with depressed mood † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Adjustment disorder with mixed disturbance of emotion and conduct † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Affect lability † 1	9/2841 (0.32%)	10	17/2902 (0.59%)	20
Affective disorder † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Aggression † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Agitated depression † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Agitation † 1	22/2841 (0.77%)	22	12/2902 (0.41%)	12
Agoraphobia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Alcohol abuse † 1	2/2841 (0.07%)	3	0/2902 (0.00%)	0
Anger † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Anhedonia † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Anxiety † 1	157/2841 (5.53%)	184	143/2902 (4.93%)	168
Anxiety disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Apathy † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Attention deficit hyperactivity disorder † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Bradyphrenia † 1	1/2841 (0.04%)	1	4/2902 (0.14%)	4
Bruxism † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Confusional state † 1	7/2841 (0.25%)	7	5/2902 (0.17%)	6
Conversion disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Daydreaming † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Delirium † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Depressed mood † 1	38/2841 (1.34%)	44	33/2902 (1.14%)	39
Depression † 1	156/2841 (5.49%)	191	150/2902 (5.17%)	175
Depressive symptom † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Disorientation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Eating disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Emotional disorder † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Emotional distress † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Female orgasmic disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Flashback † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Genito-pelvic pain/penetration disorder † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Hallucination, auditory † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Initial insomnia † 1	2/2841 (0.07%)	3	2/2902 (0.07%)	2
Insomnia † 1	383/2841 (13.48%)	468	357/2902 (12.30%)	418
Irritability † 1	30/2841 (1.06%)	34	25/2902 (0.86%)	28
Libido decreased † 1	31/2841 (1.09%)	33	34/2902 (1.17%)	38
Libido disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Loss of libido † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Mania † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mental disorder † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Middle insomnia † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Mixed anxiety and depressive disorder † 1	2/2841 (0.07%)	2	5/2902 (0.17%)	5
Mood altered † 1	20/2841 (0.70%)	23	26/2902 (0.90%)	28
Mood swings † 1	20/2841 (0.70%)	24	28/2902 (0.96%)	30
Negative thoughts † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Nervousness † 1	3/2841 (0.11%)	3	3/2902 (0.10%)	3
Nightmare † 1	2/2841 (0.07%)	3	1/2902 (0.03%)	1
Orgasm abnormal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Panic attack † 1	5/2841 (0.18%)	5	3/2902 (0.10%)	3
Paranoia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Perinatal depression † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Persistent depressive disorder † 1	4/2841 (0.14%)	5	1/2902 (0.03%)	2
Personality change † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Phonophobia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Post-traumatic stress disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Restlessness † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Seasonal affective disorder † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Sleep disorder † 1	24/2841 (0.84%)	31	26/2902 (0.90%)	33
Stress † 1	1/2841 (0.04%)	1	7/2902 (0.24%)	7
Suicidal ideation † 1	2/2841 (0.07%)	2	4/2902 (0.14%)	4
Suicide attempt † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Tearfulness † 1	2/2841 (0.07%)	3	1/2902 (0.03%)	1
Terminal insomnia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Thinking abnormal † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	3/2841 (0.11%)	3	4/2902 (0.14%)	5
Bladder discomfort † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Bladder dysfunction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bladder prolapse † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bladder spasm † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Calculus urinary † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Chromaturia † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Chronic kidney disease † 1	4/2841 (0.14%)	7	9/2902 (0.31%)	10
Cystitis noninfective † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Dysuria † 1	36/2841 (1.27%)	43	18/2902 (0.62%)	21
Haematuria † 1	13/2841 (0.46%)	13	12/2902 (0.41%)	13
Hydronephrosis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Hypercalciuria † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hypertonic bladder † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Incontinence † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Leukocyturia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Micturition urgency † 1	7/2841 (0.25%)	7	8/2902 (0.28%)	10
Nephrolithiasis † 1	6/2841 (0.21%)	6	9/2902 (0.31%)	10
Nocturia † 1	6/2841 (0.21%)	6	3/2902 (0.10%)	3
Pollakiuria † 1	30/2841 (1.06%)	33	21/2902 (0.72%)	23
Polyuria † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Proteinuria † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Renal colic † 1	1/2841 (0.04%)	1	4/2902 (0.14%)	4
Renal cyst † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Renal failure † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Renal injury † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Renal mass † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Renal pain † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Strangury † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Stress urinary incontinence † 1	3/2841 (0.11%)	3	2/2902 (0.07%)	2
Ureteric obstruction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ureteric stenosis † 1	1/2841 (0.04%)	4	0/2902 (0.00%)	0
Urge incontinence † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Urinary bladder polyp † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Urinary hesitation † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Urinary incontinence † 1	19/2841 (0.67%)	22	22/2902 (0.76%)	27
Urinary retention † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Urinary tract disorder † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Urinary tract inflammation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Urinary tract obstruction † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Urinary tract pain † 1	9/2841 (0.32%)	9	7/2902 (0.24%)	9
Urine flow decreased † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Urine odour abnormal † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Reproductive system and breast disorders
Adnexa uteri pain † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Amenorrhoea † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Anisomastia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Atrophic vulvovaginitis † 1	6/2841 (0.21%)	9	11/2902 (0.38%)	11
Bartholin's cyst † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Breast calcifications † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Breast cyst † 1	3/2841 (0.11%)	3	3/2902 (0.10%)	3
Breast discharge † 1	3/2841 (0.11%)	4	1/2902 (0.03%)	1
Breast discomfort † 1	15/2841 (0.53%)	16	9/2902 (0.31%)	9
Breast disorder † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Breast fibrosis † 1	5/2841 (0.18%)	5	10/2902 (0.34%)	10
Breast haematoma † 1	5/2841 (0.18%)	5	3/2902 (0.10%)	3
Breast hyperplasia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Breast induration † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Breast inflammation † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Breast mass † 1	12/2841 (0.42%)	13	10/2902 (0.34%)	10
Breast necrosis † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Breast oedema † 1	20/2841 (0.70%)	21	18/2902 (0.62%)	18
Breast pain † 1	145/2841 (5.10%)	163	158/2902 (5.44%)	186
Breast swelling † 1	7/2841 (0.25%)	7	13/2902 (0.45%)	14
Breast tenderness † 1	2/2841 (0.07%)	2	17/2902 (0.59%)	17
Breast ulceration † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Cervical dysplasia † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Cervical polyp † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Coital bleeding † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Dysmenorrhoea † 1	3/2841 (0.11%)	3	4/2902 (0.14%)	4
Dyspareunia † 1	37/2841 (1.30%)	43	35/2902 (1.21%)	38
Endometrial atrophy † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Endometrial disorder † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Endometrial hyperplasia † 1	8/2841 (0.28%)	8	9/2902 (0.31%)	9
Endometrial hypertrophy † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Endometrial thickening † 1	2/2841 (0.07%)	3	0/2902 (0.00%)	0
Endometriosis † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Fibrocystic breast disease † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Genital haemorrhage † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Genital lesion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Gynaecomastia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Menopausal disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Menopausal symptoms † 1	6/2841 (0.21%)	7	2/2902 (0.07%)	2
Menorrhagia † 1	7/2841 (0.25%)	7	12/2902 (0.41%)	15
Menstrual disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Menstruation irregular † 1	7/2841 (0.25%)	7	9/2902 (0.31%)	10
Metrorrhagia † 1	3/2841 (0.11%)	3	5/2902 (0.17%)	5
Nipple disorder † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Nipple exudate bloody † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nipple pain † 1	0/2841 (0.00%)	0	4/2902 (0.14%)	4
Ovarian cyst † 1	7/2841 (0.25%)	7	12/2902 (0.41%)	13
Ovarian disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ovarian mass † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Pelvic adhesions † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Pelvic floor muscle weakness † 1	1/2841 (0.04%)	1	4/2902 (0.14%)	4
Pelvic pain † 1	16/2841 (0.56%)	18	21/2902 (0.72%)	23
Perineal pain † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Postmenopausal haemorrhage † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Premature menopause † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Prostatitis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Reproductive tract disorder † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Retracted nipple † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Uterine haemorrhage † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	2
Uterine polyp † 1	5/2841 (0.18%)	5	7/2902 (0.24%)	8
Uterine prolapse † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Uterine spasm † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vaginal discharge † 1	31/2841 (1.09%)	32	42/2902 (1.45%)	49
Vaginal haemorrhage † 1	43/2841 (1.51%)	46	68/2902 (2.34%)	79
Vaginal lesion † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vaginal prolapse † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Vulvovaginal burning sensation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Vulvovaginal discomfort † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Vulvovaginal dryness † 1	182/2841 (6.41%)	211	213/2902 (7.34%)	254
Vulvovaginal inflammation † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Vulvovaginal pain † 1	3/2841 (0.11%)	3	4/2902 (0.14%)	5
Vulvovaginal pruritus † 1	12/2841 (0.42%)	15	11/2902 (0.38%)	14
Respiratory, thoracic and mediastinal disorders
Allergic bronchitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Allergic cough † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Allergic respiratory symptom † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Allergic sinusitis † 1	1/2841 (0.04%)	2	1/2902 (0.03%)	1
Aphonia † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Apnoea † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Asphyxia † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Aspiration † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Asthma † 1	8/2841 (0.28%)	8	4/2902 (0.14%)	4
Asthma exercise induced † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Atelectasis † 1	1/2841 (0.04%)	1	3/2902 (0.10%)	3
Bronchial disorder † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bronchial hyperreactivity † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bronchial obstruction † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Bronchiectasis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Bronchitis chronic † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Bronchospasm † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	3
Catarrh † 1	8/2841 (0.28%)	10	5/2902 (0.17%)	6
Chronic obstructive pulmonary disease † 1	4/2841 (0.14%)	6	3/2902 (0.10%)	3
Cough † 1	416/2841 (14.64%)	543	222/2902 (7.65%)	256
Cough variant asthma † 1	1/2841 (0.04%)	5	0/2902 (0.00%)	0
Dry throat † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	2
Dysphonia † 1	29/2841 (1.02%)	31	9/2902 (0.31%)	9
Dyspnoea † 1	197/2841 (6.93%)	247	130/2902 (4.48%)	144
Dyspnoea exertional † 1	31/2841 (1.09%)	31	12/2902 (0.41%)	12
Dyspnoea paroxysmal nocturnal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Emphysema † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Epistaxis † 1	108/2841 (3.80%)	131	16/2902 (0.55%)	16
Haemoptysis † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Hiccups † 1	8/2841 (0.28%)	8	0/2902 (0.00%)	0
Hyperventilation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hypoxia † 1	2/2841 (0.07%)	4	2/2902 (0.07%)	2
Increased bronchial secretion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Interstitial lung disease † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Laryngeal inflammation † 1	5/2841 (0.18%)	5	3/2902 (0.10%)	3
Laryngeal oedema † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Laryngeal pain † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Lung disorder † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Lymphangioleiomyomatosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Nasal congestion † 1	98/2841 (3.45%)	118	26/2902 (0.90%)	29
Nasal discomfort † 1	7/2841 (0.25%)	9	0/2902 (0.00%)	0
Nasal disorder † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Nasal dryness † 1	18/2841 (0.63%)	19	1/2902 (0.03%)	1
Nasal inflammation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nasal polyps † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nasal pruritus † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nasal septum deviation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nasal turbinate hypertrophy † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nasal ulcer † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Oropharyngeal discomfort † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Oropharyngeal pain † 1	155/2841 (5.46%)	169	60/2902 (2.07%)	65
Orthopnoea † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Painful respiration † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Paranasal sinus discomfort † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Pharyngeal erythema † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pharyngeal inflammation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pharyngeal paraesthesia † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Pharyngeal swelling † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Pleural effusion † 1	8/2841 (0.28%)	8	3/2902 (0.10%)	3
Pleurisy † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Pleuritic pain † 1	3/2841 (0.11%)	5	2/2902 (0.07%)	2
Pneumonitis † 1	9/2841 (0.32%)	11	5/2902 (0.17%)	5
Productive cough † 1	41/2841 (1.44%)	45	21/2902 (0.72%)	24
Pulmonary congestion † 1	6/2841 (0.21%)	7	1/2902 (0.03%)	1
Pulmonary embolism † 1	9/2841 (0.32%)	9	4/2902 (0.14%)	4
Pulmonary fibrosis † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Pulmonary hypertension † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Pulmonary infarction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Pulmonary mass † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Pulmonary sarcoidosis † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Respiratory disorder † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Respiratory distress † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Respiratory symptom † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Respiratory tract irritation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Rhinalgia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Rhinitis allergic † 1	42/2841 (1.48%)	48	24/2902 (0.83%)	25
Rhinitis atrophic † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Rhinorrhoea † 1	52/2841 (1.83%)	56	16/2902 (0.55%)	16
Sinus congestion † 1	15/2841 (0.53%)	15	4/2902 (0.14%)	4
Sinus disorder † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Sinus pain † 1	9/2841 (0.32%)	11	4/2902 (0.14%)	4
Sleep apnoea syndrome † 1	5/2841 (0.18%)	9	9/2902 (0.31%)	9
Sneezing † 1	5/2841 (0.18%)	5	1/2902 (0.03%)	1
Snoring † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Sputum increased † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Throat irritation † 1	3/2841 (0.11%)	4	1/2902 (0.03%)	1
Throat lesion † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Throat tightness † 1	1/2841 (0.04%)	1	4/2902 (0.14%)	5
Tonsillar hypertrophy † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Tonsillar ulcer † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Tonsillolith † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Upper respiratory tract congestion † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Upper respiratory tract irritation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Upper-airway cough syndrome † 1	32/2841 (1.13%)	36	19/2902 (0.65%)	20
Vocal cord atrophy † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Vocal cord dysfunction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Wheezing † 1	7/2841 (0.25%)	10	10/2902 (0.34%)	15
Skin and subcutaneous tissue disorders
Acne † 1	11/2841 (0.39%)	12	4/2902 (0.14%)	5
Actinic keratosis † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Alopecia † 1	510/2841 (17.95%)	558	149/2902 (5.13%)	163
Alopecia totalis † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Blister † 1	11/2841 (0.39%)	13	2/2902 (0.07%)	2
Blood blister † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Capillaritis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Chloasma † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Chronic pigmented purpura † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Cold sweat † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Cutaneous lupus erythematosus † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Cutaneous symptom † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Dermal cyst † 1	4/2841 (0.14%)	4	7/2902 (0.24%)	7
Dermatitis † 1	11/2841 (0.39%)	11	12/2902 (0.41%)	12
Dermatitis acneiform † 1	32/2841 (1.13%)	39	13/2902 (0.45%)	15
Dermatitis allergic † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Dermatitis bullous † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Dermatitis contact † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Dermatomyositis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Drug eruption † 1	1/2841 (0.04%)	5	1/2902 (0.03%)	1
Dry skin † 1	153/2841 (5.39%)	178	56/2902 (1.93%)	67
Dyshidrotic eczema † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ecchymosis † 1	3/2841 (0.11%)	4	1/2902 (0.03%)	1
Eczema † 1	22/2841 (0.77%)	24	13/2902 (0.45%)	14
Eczema nummular † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Erythema † 1	54/2841 (1.90%)	56	42/2902 (1.45%)	45
Erythema multiforme † 1	3/2841 (0.11%)	5	1/2902 (0.03%)	1
Hair growth abnormal † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Hair texture abnormal † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Hand dermatitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hidradenitis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Hirsutism † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Hyperhidrosis † 1	38/2841 (1.34%)	40	31/2902 (1.07%)	36
Hyperkeratosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hypertrichosis † 1	4/2841 (0.14%)	4	2/2902 (0.07%)	2
Hypertrophic scar † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Idiopathic urticaria † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Ingrowing nail † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	3
Intertrigo † 1	0/2841 (0.00%)	0	3/2902 (0.10%)	3
Itching scar † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Keloid scar † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
Lichen planus † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	3
Lichen sclerosus † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Lichenoid keratosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Madarosis † 1	22/2841 (0.77%)	25	4/2902 (0.14%)	4
Milia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Miliaria † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Myxoid cyst † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Nail bed disorder † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Nail bed inflammation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Nail discolouration † 1	9/2841 (0.32%)	9	3/2902 (0.10%)	3
Nail disorder † 1	31/2841 (1.09%)	35	11/2902 (0.38%)	13
Nail dystrophy † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Nail ridging † 1	10/2841 (0.35%)	10	3/2902 (0.10%)	3
Nail toxicity † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Neurodermatitis † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	2
Night sweats † 1	42/2841 (1.48%)	50	50/2902 (1.72%)	53
Onychalgia † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Onychoclasis † 1	29/2841 (1.02%)	29	3/2902 (0.10%)	3
Onycholysis † 1	4/2841 (0.14%)	4	3/2902 (0.10%)	3
Onychomadesis † 1	16/2841 (0.56%)	16	9/2902 (0.31%)	9
Pain of skin † 1	14/2841 (0.49%)	15	1/2902 (0.03%)	1
Palmar-plantar erythrodysaesthesia syndrome † 1	10/2841 (0.35%)	11	1/2902 (0.03%)	1
Panniculitis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Papule † 1	2/2841 (0.07%)	2	2/2902 (0.07%)	2
Papulopustular rosacea † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Peau d'orange † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Perioral dermatitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Petechiae † 1	4/2841 (0.14%)	5	1/2902 (0.03%)	1
Photodermatosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Photosensitivity reaction † 1	7/2841 (0.25%)	7	2/2902 (0.07%)	2
Pigmentation disorder † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Pityriasis rosea † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Plantar erythema † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Prurigo † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Pruritus † 1	183/2841 (6.44%)	222	95/2902 (3.27%)	105
Psoriasis † 1	7/2841 (0.25%)	10	7/2902 (0.24%)	7
Purpura † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Rash † 1	229/2841 (8.06%)	288	90/2902 (3.10%)	102
Rash erythematous † 1	2/2841 (0.07%)	2	5/2902 (0.17%)	5
Rash follicular † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Rash macular † 1	6/2841 (0.21%)	6	3/2902 (0.10%)	4
Rash maculo-papular † 1	65/2841 (2.29%)	108	25/2902 (0.86%)	32
Rash papular † 1	4/2841 (0.14%)	4	1/2902 (0.03%)	1
Rash pruritic † 1	12/2841 (0.42%)	12	9/2902 (0.31%)	11
Rosacea † 1	10/2841 (0.35%)	10	4/2902 (0.14%)	4
Scab † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Scar pain † 1	15/2841 (0.53%)	16	23/2902 (0.79%)	26
Sebaceous hyperplasia † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Seborrhoeic dermatitis † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Sensitive skin † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Skin atrophy † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Skin burning sensation † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Skin discolouration † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	4
Skin discomfort † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Skin disorder † 1	4/2841 (0.14%)	5	9/2902 (0.31%)	10
Skin exfoliation † 1	10/2841 (0.35%)	10	4/2902 (0.14%)	4
Skin fissures † 1	7/2841 (0.25%)	8	0/2902 (0.00%)	0
Skin hyperpigmentation † 1	11/2841 (0.39%)	13	17/2902 (0.59%)	18
Skin hypertrophy † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Skin hypopigmentation † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Skin induration † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Skin irritation † 1	7/2841 (0.25%)	7	1/2902 (0.03%)	1
Skin lesion † 1	17/2841 (0.60%)	18	9/2902 (0.31%)	11
Skin mass † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Skin oedema † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Skin plaque † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Skin reaction † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Skin striae † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Skin tightness † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Skin toxicity † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Skin ulcer † 1	7/2841 (0.25%)	9	2/2902 (0.07%)	2
Skin warm † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Skin weeping † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Solar lentigo † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Stevens-Johnson syndrome † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Telangiectasia † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Toxic skin eruption † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Trichorrhexis † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Urticaria † 1	24/2841 (0.84%)	29	11/2902 (0.38%)	12
Vitiligo † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Xeroderma † 1	2/2841 (0.07%)	5	2/2902 (0.07%)	2
Social circumstances
Postmenopause † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Sight disability † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Surgical and medical procedures
Breast operation † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Breast prosthesis removal † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Breast reconstruction † 1	9/2841 (0.32%)	11	7/2902 (0.24%)	9
Cataract operation † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Central venous catheter removal † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Cholecystectomy † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Dental care † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Dental operation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Drain removal † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Endodontic procedure † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hernia repair † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Hip arthroplasty † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Hysterosalpingo-oophorectomy † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Incisional drainage † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Infection prophylaxis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Joint dislocation reduction † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Lipoma excision † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Mammoplasty † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Medical device removal † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Medical procedure † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Meniscus operation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Metabolic surgery † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Micrographic skin surgery † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
Mole excision † 1	2/2841 (0.07%)	2	1/2902 (0.03%)	1
Nail operation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Oophorectomy † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Post procedural drainage † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	2
Salpingo-oophorectomy bilateral † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Sinus operation † 1	5/2841 (0.18%)	5	0/2902 (0.00%)	0
Skin lesion removal † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Skin neoplasm excision † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Spinal operation † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Surgery † 1	4/2841 (0.14%)	5	1/2902 (0.03%)	1
Tendon sheath incision † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Thyroid operation † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Tooth extraction † 1	2/2841 (0.07%)	3	0/2902 (0.00%)	0
Weight loss diet † 1	3/2841 (0.11%)	3	1/2902 (0.03%)	1
Wound drainage † 1	3/2841 (0.11%)	3	0/2902 (0.00%)	0
Vascular disorders
Angiopathy † 1	2/2841 (0.07%)	2	3/2902 (0.10%)	3
Aortic aneurysm † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Aortic arteriosclerosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Aortic dilatation † 1	1/2841 (0.04%)	1	1/2902 (0.03%)	1
Arterial thrombosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Arteriosclerosis † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Arteriovenous fistula † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Axillary vein thrombosis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Bleeding varicose vein † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Blood pressure inadequately controlled † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Capillary fragility † 1	5/2841 (0.18%)	5	1/2902 (0.03%)	1
Deep vein thrombosis † 1	9/2841 (0.32%)	9	5/2902 (0.17%)	8
Embolism † 1	9/2841 (0.32%)	9	3/2902 (0.10%)	4
Essential hypertension † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	2
Flushing † 1	15/2841 (0.53%)	20	24/2902 (0.83%)	33
Haematoma † 1	20/2841 (0.70%)	20	7/2902 (0.24%)	7
Hot flush † 1	702/2841 (24.71%)	887	849/2902 (29.26%)	1066
Hypertension † 1	205/2841 (7.22%)	363	227/2902 (7.82%)	382
Hypertensive crisis † 1	2/2841 (0.07%)	3	1/2902 (0.03%)	1
Hypotension † 1	28/2841 (0.99%)	31	16/2902 (0.55%)	16
Intermittent claudication † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lymphocele † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Lymphoedema † 1	336/2841 (11.83%)	395	268/2902 (9.24%)	303
Orthostatic hypotension † 1	1/2841 (0.04%)	1	2/2902 (0.07%)	2
Peripheral coldness † 1	3/2841 (0.11%)	3	3/2902 (0.10%)	3
Peripheral venous disease † 1	6/2841 (0.21%)	7	2/2902 (0.07%)	2
Phlebitis † 1	6/2841 (0.21%)	7	6/2902 (0.21%)	8
Poor peripheral circulation † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Post thrombotic syndrome † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Prehypertension † 1	0/2841 (0.00%)	0	1/2902 (0.03%)	1
Raynaud's phenomenon † 1	3/2841 (0.11%)	4	1/2902 (0.03%)	1
Subclavian vein thrombosis † 1	2/2841 (0.07%)	2	0/2902 (0.00%)	0
Thrombophlebitis † 1	5/2841 (0.18%)	7	3/2902 (0.10%)	3
Thrombophlebitis superficial † 1	5/2841 (0.18%)	6	5/2902 (0.17%)	5
Thrombosis † 1	8/2841 (0.28%)	11	2/2902 (0.07%)	2
Varicophlebitis † 1	1/2841 (0.04%)	1	0/2902 (0.00%)	0
Varicose vein † 1	4/2841 (0.14%)	4	4/2902 (0.14%)	5
Venous thrombosis † 1	1/2841 (0.04%)	2	0/2902 (0.00%)	0
White coat hypertension † 1	0/2841 (0.00%)	0	2/2902 (0.07%)	2
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Erica L. Mayer, MD, MPH
• Organization: Dana-Farber Cancer Institute
• Phone: 617-632-3800
• EMail: emayer@partners.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mayer EL, Fesl C, Hlauschek D, Garcia-Estevez L, Burstein HJ, Zdenkowski N, Wette V, Miller KD, Balic M, Mayer IA, Cameron D, Winer EP, Ponce Lorenzo JJ, Lake D, Pristauz-Telsnigg G, Haddad TC, Shepherd L, Iwata H, Goetz M, Cardoso F, Traina TA, Sabanathan D, Breitenstein U, Ackerl K, Metzger Filho O, Zehetner K, Solomon K, El-Abed S, Theall KP, Lu DR, Dueck A, Gnant M, DeMichele A. Treatment Exposure and Discontinuation in the PALbociclib CoLlaborative Adjuvant Study of Palbociclib With Adjuvant Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer (PALLAS/AFT-05/ABCSG-42/BIG-14-03). J Clin Oncol. 2022 Feb 10;40(5):449-458. doi: 10.1200/JCO.21.01918. Epub 2022 Jan 7.

Gnant M, Dueck AC, Frantal S, Martin M, Burstein HJ, Greil R, Fox P, Wolff AC, Chan A, Winer EP, Pfeiler G, Miller KD, Colleoni M, Suga JM, Rubovsky G, Bliss JM, Mayer IA, Singer CF, Nowecki Z, Hahn O, Thomson J, Wolmark N, Amillano K, Rugo HS, Steger GG, Hernando Fernandez de Aranguiz B, Haddad TC, Perello A, Bellet M, Fohler H, Metzger Filho O, Jallitsch-Halper A, Solomon K, Schurmans C, Theall KP, Lu DR, Tenner K, Fesl C, DeMichele A, Mayer EL; PALLAS groups and investigators. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022 Jan 20;40(3):282-293. doi: 10.1200/JCO.21.02554. Epub 2021 Dec 7.

Mayer EL, Dueck AC, Martin M, Rubovszky G, Burstein HJ, Bellet-Ezquerra M, Miller KD, Zdenkowski N, Winer EP, Pfeiler G, Goetz M, Ruiz-Borrego M, Anderson D, Nowecki Z, Loibl S, Moulder S, Ring A, Fitzal F, Traina T, Chan A, Rugo HS, Lemieux J, Henao F, Lyss A, Antolin Novoa S, Wolff AC, Vetter M, Egle D, Morris PG, Mamounas EP, Gil-Gil MJ, Prat A, Fohler H, Metzger Filho O, Schwarz M, DuFrane C, Fumagalli D, Theall KP, Lu DR, Bartlett CH, Koehler M, Fesl C, DeMichele A, Gnant M. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021 Feb;22(2):212-222. doi: 10.1016/S1470-2045(20)30642-2. Epub 2021 Jan 15.

Dieras V, Rugo HS, Schnell P, Gelmon K, Cristofanilli M, Loi S, Colleoni M, Lu DR, Mori A, Gauthier E, Huang Bartlett C, Slamon DJ, Turner NC, Finn RS. Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer. J Natl Cancer Inst. 2019 Apr 1;111(4):419-430. doi: 10.1093/jnci/djy109.

• Responsible Party: Alliance Foundation Trials, LLC.
• ClinicalTrials.gov Identifier: NCT02513394
• Other Study ID Numbers: AFT-05; ABCSG 42 ( Other Identifier: ABCSG GmbH ); BIG 14-03 ( Other Identifier: Breast International Group ); 2014-005181-30 ( EudraCT Number )
• First Submitted: July 29, 2015
• First Posted: July 31, 2015
• Results First Submitted: February 1, 2022
• Results First Posted: April 13, 2022
• Last Update Posted: January 24, 2024