Pooled safety profile of oral donepezil in Phase 3 placebo-controlled trials1

Adverse reactions occurring in ≥2% of patients receiving oral donepezil 5 mg/d
or 10 mg/d and at a greater incidence than in patients receiving placebo

Mild to moderate
Alzheimer's disease

Severe
Alzheimer's disease

Placebo

(n=355)

%

Oral donepezil

(n=747)

%

Placebo

(n=392)

%

Oral donepezil

(n=501)

%

Patients with any
adverse reaction
72 74 73 81
Nausea 6 11 2 6
Infection - - 9 11
Diarrhea 5 10 4 10
Headache 9 10 3 4
Insomnia 6 9 4 5
Pain, various locations 8 9 - -
Dizziness 6 8 1 2
Accident 6 7 12 13
Muscle cramps 2 6 - -
Fatigue 3 5 - -
Vomiting 3 5 4 8
Anorexia 2 4 4 8
Ecchymosis 3 4 2 5
Abnormal dreams 0 3 - -
Depression <1 3 1 2
Weight loss 1 3 - -
Hypertension - - 2 3
Pain - - 2 3
Back pain - - 2 3
Eczema - - 2 3
Hallucinations - - 1 3
Hostility - - 2 3
Increase in creatine phosphokinase - - 1 3
Nervousness - - 2 3
Arthritis 1 2 - -
Frequent urination 1 2 - -
Somnolence <1 2 1 2
Syncope 1 2 1 2
Fever - - 1 2
Chest pain - - <1 2
Confusion - - 1 2
Dehydration - - 1 2
Emotional lability - - 1 2
Hemorrhage - - 1 2
Hyperlipemia - - <1 2
Personality disorder - - 1 2
Urinary incontinence - - 1 2

Mild to moderate
Alzheimer's disease

Placebo

(n=355)

%

Oral donepezil

(n=747)

%

Patients with any
adverse reaction
72 74
Nausea 6 11
Infection - -
Diarrhea 5 10
Headache 9 10
Insomnia 6 9
Pain, various locations 8 9
Dizziness 6 8
Accident 6 7
Muscle cramps 2 6
Fatigue 3 5
Vomiting 3 5
Anorexia 2 4
Ecchymosis 3 4
Abnormal dreams 0 3
Depression <1 3
Weight loss 1 3
Hypertension - -
Pain - -
Back pain - -
Eczema - -
Hallucinations - -
Hostility - -
Increase in creatine phosphokinase - -
Nervousness - -
Arthritis 1 2
Frequent urination 1 2
Somnolence <1 2
Syncope 1 2
Fever - -
Chest pain - -
Confusion - -
Dehydration - -
Emotional lability - -
Hemorrhage - -
Hyperlipemia - -
Personality disorder - -
Urinary incontinence - -

Severe
Alzheimer's disease

Placebo

(n=392)

%

Oral donepezil

(n=501)

%

Patients with any
adverse reaction
73 81
Nausea 2 6
Infection 9 11
Diarrhea 4 10
Headache 3 4
Insomnia 4 5
Pain, various locations - -
Dizziness 1 2
Accident 12 13
Muscle cramps - -
Fatigue - -
Vomiting 4 8
Anorexia 4 8
Ecchymosis 2 5
Abnormal dreams - -
Depression 1 2
Weight loss - -
Hypertension 2 3
Pain 2 3
Back pain 2 3
Eczema 2 3
Hallucinations 1 3
Hostility 2 3
Increase in creatine phosphokinase 1 3
Nervousness 2 3
Arthritis - -
Frequent urination - -
Somnolence 1 2
Syncope 1 2
Fever 1 2
Chest pain <1 2
Confusion 1 2
Dehydration 1 2
Emotional lability 1 2
Hemorrhage 1 2
Hyperlipemia <1 2
Personality disorder 1 2
Urinary incontinence 1 2
Reference: 1. ADLARITY. Prescribing information. Corium, Inc; 2022.