Clinical Studies
Mild to Moderately Severe Alzheimer’s Disease
The most common adverse events (incidence ≥5% and twice the frequency of placebo in patients receiving 10 mg/day) were diarrhea, muscle cramps, fatigue, nausea, vomiting and insomnia (see Table 1).
Other common adverse events (incidence ≥5% and ≥ placebo) were headache, pain, accident, common cold, abdominal disturbance and dizziness. Cases of syncope, bradycardia, sinoatrial block and atrioventricular block were observed. No notable abnormalities in laboratory values associated with treatment were observed except for minor increases in serum concentrations of muscle creatinine kinase.
| Table 1 – Adverse Events Reported in Controlled Clinical Trials in Mild to Moderately Severe Alzheimer’s Disease in at Least 2% of Patients Receiving Donepezil Hydrochloride and at a Higher Frequency than Placebo-Treated Patients | ||
| BODY SYSTEM/ ADVERSE EVENT | Donepezil (n=747) | Placebo (n=355) |
| Percent of Patients with any Adverse Event | 74% | 72% |
| Body as a whole | ||
| Headache | 10% | 9% |
| Pain, various locations | 9% | 8% |
| Accident | 7% | 6% |
| Fatigue | 5% | 3% |
| Cardiovascular | ||
| Syncope | 2% | 1% |
| Digestive System | ||
| Nausea | 11% | 6% |
| Diarrhea | 10% | 5% |
| Vomiting | 5% | 3% |
| Anorexia | 4% | 2% |
| Musculoskeletal System | ||
| Muscle Cramps | 6% | 2% |
| Nervous System | ||
| Insomnia | 9% | 6% |
| Dizziness | 8% | 6% |
| Psychiatric System | ||
| Abnormal Dreams | 3% | 0% |
Severe Alzheimer’s Disease
The most common adverse events (incidence ≥5% and twice the frequency of placebo) were diarrhea, nausea, and aggression (see Table 2).
| Table 2 – Adverse Events Reported in Controlled Clinical Trials in Severe Alzheimer’s Disease in at Least 5% of Patients Receiving Donepezil Hydrochloride and at a Higher Frequency than Placebo-Treated Patients | ||
| BODY SYSTEM/ADVERSE EVENT | Donepezil (N=573, 477 randomized 10mg, 96 randomized to 5mg) (%) | Placebo (N=465) (%) |
| Total number of patients with an adverse event (all causalities) | 80.8 | 74 |
| Diarrhea | 10.3 | 4.1 |
| Fall | 10.1 | 8.8 |
| Urinary Tract Infection | 8.2 | 7.1 |
| Nasopharyngitis | 8.2 | 6.2 |
| Vomiting | 7.5 | 3.9 |
| Agitation | 6.3 | 6.5 |
| Nausea | 5.6 | 2.6 |
| Headache | 5.1 | 3 |
| Aggression | 5.1 | 2.4 |
Vascular Dementia
A comparison of the Alzheimer’s disease and vascular dementia studies shows that the types of and relative proportions of adverse events associated with donepezil hydrochloride were similar in the two populations. In the combined vascular dementia studies the mortality rate in the donepezil hydrochloride group (1.7%) was numerically higher than in the placebo group (1.1 %).
Dementia with Lewy Bodies
The safety profile observed in the Phase 3 study in patients with Dementia with Lewy Bodies was similar to the safety profile observed in the studies in Alzheimer’s Disease with the exception of a higher rate of Parkinsonism.
Post-Marketing Experience
There have been post-marketing reports of hallucinations, agitation, aggressive behavior, seizure, hepatitis, gastric ulcer, duodenal ulcer, and gastrointestinal hemorrhage.
| Reporting of suspected adverse drug reactions |
| Please contact: |
| HI-Eisai Pharmaceutical, Inc. |
| +63 2 88875837 / +63 2 88875160 / +63 9088672236 |
| Or Report to FDA Philippines: www.fda.gov.ph |