donepezil hydrochloride
Generic: DONEPEZIL HYDROCHLORIDE
Basic Information
Manufacturer
A-S Medication Solutions
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
5d46ef3c-0dee-4389-a2d5-997ea8342817
Indications & Usage
1 INDICATIONS AND USAGE Donepezil hydrochloride is indicated for the treatment of dementia of the Alzheimer's type.
Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer's disease.
Donepezil hydrochloride is an acetylcholinesterase inhibitor indicated for the treatment of dementia of the Alzheimer's type.
Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer's Disease ( 1 ).
Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer's disease.
Donepezil hydrochloride is an acetylcholinesterase inhibitor indicated for the treatment of dementia of the Alzheimer's type.
Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer's Disease ( 1 ).
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: • Cardiovascular Conditions [see Warnings and Precautions ( 5.2 )] • Nausea and Vomiting [see Warnings and Precautions ( 5.3 )] • Peptic Ulcer Disease and GI Bleeding [see Warnings and Precautions ( 5.4 )] • Genitourinary Conditions [see Warnings and Precautions ( 5.6 )] • Neurological Conditions: Seizures [see Warnings and Precautions ( 5.7 )] • Pulmonary Conditions [see Warnings and Precautions ( 5.8 )] Most common adverse reactions in clinical studies of donepezil hydrochloride are nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia ( 6.1 ).
To report SUSPECTED ADVERSE REACTIONS, contact Solco Healthcare US, LLC at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Donepezil hydrochloride has been administered to over 1,700 individuals during clinical trials worldwide.
Approximately 1200 of these patients have been treated for at least 3 months and more than 1,000 patients have been treated for at least 6 months.
Controlled and uncontrolled trials in the United States included approximately 900 patients.
In regards to the highest dose of 10 mg/day, this population includes 650 patients treated for 3 months, 475 patients treated for 6 months, and 116 patients treated for over 1 year.
The range of patient exposure is from 1 to 1,214 days.
Mild to Moderate Alzheimer’s Disease Adverse Reactions Leading to Discontinuation The rates of discontinuation from controlled clinical trials of donepezil hydrochloride due to adverse reactions for the donepezil hydrochloride 5 mg/day treatment groups were comparable to those of placebo treatment groups at approximately 5%.
The rate of discontinuation of patients who received 7-day escalations from 5 mg/day to 10 mg/day was higher at 13%.
The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of patients and at twice or more the incidence seen in placebo patients, are shown in Table 1.
Table 1.
Most Common Adverse Reactions Leading to Discontinuation in Patients with Mild to Moderate Alzheimer’s Disease Adverse Reaction Placebo (n=355) % 5 mg/day Donepezil Hydrochloride (n=350) % 10 mg/day Donepezil Hydrochloride (n=315) % Nausea 1 1 3 Diarrhea 0 <1 3 Vomiting <1 <1 2 Most Common Adverse Reactions The most common adverse reactions, defined as those occurring at a frequency of at least 5% in patients receiving 10 mg/day and twice the placebo rate, are largely predicted by donepezil hydrochloride’s cholinomimetic effects.
These include nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue, and anorexia.
These adverse reactions were often transient, resolving during continued donepezil hydrochloride treatment without the need for dose modification.
There is evidence to suggest that the frequency of these common adverse reactions may be affected by the rate of titration.
An open-label study was conducted with 269 patients who received placebo in the 15- and 30-week studies.
These patients were titrated to a dose of 10 mg/day over a 6-week period.
The rates of common adverse reactions were lower than those seen in patients titrated to 10 mg/day over one week in the controlled clinical trials and were comparable to those seen in patients on 5 mg/day.
See Table 2 for a comparison of the most common adverse reactions following one and six week titration regimens.
Table 2.
Comparison of Rates of Adverse Reactions in Mild to Moderate Patients Titrated to 10 mg/day over 1 and 6 Weeks No titration One week titration Six week titration Adverse Reaction Placebo (n=315) % 5 mg/day (n=311) % 10 mg/day (n=315) 5 10 mg/day (n=269) % Nausea 6 5 19 6 Diarrhea 5 8 15 9 Insomnia 6 6 14 6 Fatigue 3 4 8 3 Vomiting 3 3 8 5 Muscle cramps 2 6 8 3 Anorexia 2 3 7 3 Table 3 lists adverse reactions that occurred in at least 2% of patients in pooled placebo-controlled trials who received either donepezil hydrochloride 5 mg or 10 mg and for which the rate of occurrence was greater for patients treated with donepezil hydrochloride than with placebo.
In general, adverse reactions occurred more frequently in female patients and with advancing age.
Table 3.
Adverse Reactions in Pooled Placebo-Controlled Clinical Trials in Mild to Moderate Alzheimer’s Disease Adverse Reaction Placebo (n=355) % Donepezil Hydrochloride (n=747) % Percent of Patients with any Adverse Reaction 72 74 Nausea 6 11 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 Arthritis 1 2 Frequent Urination 1 2 Somnolence <1 2 Syncope 1 2 Severe Alzheimer's Disease Severe Alzheimer’s Disease (donepezil hydrochloride 5 mg/day and 10 mg/day) Donepezil hydrochloride has been administered to over 600 patients with severe Alzheimer’s disease during clinical trials of at least 6 months duration, including three double-blind, placebo-controlled trials, two of which had an open label extension. Adverse Reactions Leading to Discontinuation The rates of discontinuation from controlled clinical trials of donepezil hydrochloride due to adverse reactions for the donepezil hydrochloride patients were approximately 12% compared to 7% for placebo patients.
The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of donepezil hydrochloride patients and at twice or more the incidence seen in placebo, were anorexia (2% vs.
1% placebo), nausea (2% vs.
<1% placebo), diarrhea (2% vs.
0% placebo) and urinary tract infection (2% vs.
1% placebo).
Most Common Adverse Reactions The most common adverse reactions, defined as those occurring at a frequency of at least 5% in patients receiving donepezil hydrochloride and at twice or more the placebo rate, are largely predicted by donepezil hydrochloride’s cholinomimetic effects.
These include diarrhea, anorexia, vomiting, nausea, and ecchymosis.
These adverse reactions were often transient, resolving during continued donepezil hydrochloride treatment without the need for dose modification.
Table 4 lists adverse reactions that occurred in at least 2% of patients in pooled placebo-controlled trials who received donepezil hydrochloride 5 mg or 10 mg and for which the rate of occurrence was greater for patients treated with donepezil hydrochloride than with placebo.
Table 4.
Adverse Reactions in Pooled Controlled Clinical Trials in Severe Alzheimer’s Disease Body System/Adverse Reaction Placebo (n=392) % Donepezil Hydrochloride (n=501) % Percent of Patients with any Adverse Reaction 73 81 Accident 12 13 Infection 9 11 Diarrhea 3 4 Anorexia 2 3 Vomiting 2 3 Nausea 1 2 Insomnia <1 2 Ecchymosis 2 3 Headache 1 2 Pain 1 2 Back Pain 4 10 Eczema 4 8 Hallucinations 4 8 Hostility 2 6 Increase in Creatine Phosphokinase 2 5 Nervousness 1 3 Fever 1 2 Chest Pain <1 2 Confusion 4 5 Dehydration 2 3 Depression 2 3 Dizziness 1 3 Emotional Lability 1 2 Hemorrhage 1 2 Hyperlipemia 1 2 Personality Disorder 1 2 Somnolence 1 2 Personality Disorder 1 2 Syncope 2 3 Urinary Incontinence 1 2 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of donepezil hydrochloride.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Abdominal pain, agitation, aggression, cholecystitis, confusion, convulsions, hallucinations, heart block (all types), hemolytic anemia, hepatitis, hyponatremia, neuroleptic malignant syndrome, pancreatitis, rash, rhabdomyolysis, QTc prolongation, and torsade de pointes.
To report SUSPECTED ADVERSE REACTIONS, contact Solco Healthcare US, LLC at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Donepezil hydrochloride has been administered to over 1,700 individuals during clinical trials worldwide.
Approximately 1200 of these patients have been treated for at least 3 months and more than 1,000 patients have been treated for at least 6 months.
Controlled and uncontrolled trials in the United States included approximately 900 patients.
In regards to the highest dose of 10 mg/day, this population includes 650 patients treated for 3 months, 475 patients treated for 6 months, and 116 patients treated for over 1 year.
The range of patient exposure is from 1 to 1,214 days.
Mild to Moderate Alzheimer’s Disease Adverse Reactions Leading to Discontinuation The rates of discontinuation from controlled clinical trials of donepezil hydrochloride due to adverse reactions for the donepezil hydrochloride 5 mg/day treatment groups were comparable to those of placebo treatment groups at approximately 5%.
The rate of discontinuation of patients who received 7-day escalations from 5 mg/day to 10 mg/day was higher at 13%.
The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of patients and at twice or more the incidence seen in placebo patients, are shown in Table 1.
Table 1.
Most Common Adverse Reactions Leading to Discontinuation in Patients with Mild to Moderate Alzheimer’s Disease Adverse Reaction Placebo (n=355) % 5 mg/day Donepezil Hydrochloride (n=350) % 10 mg/day Donepezil Hydrochloride (n=315) % Nausea 1 1 3 Diarrhea 0 <1 3 Vomiting <1 <1 2 Most Common Adverse Reactions The most common adverse reactions, defined as those occurring at a frequency of at least 5% in patients receiving 10 mg/day and twice the placebo rate, are largely predicted by donepezil hydrochloride’s cholinomimetic effects.
These include nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue, and anorexia.
These adverse reactions were often transient, resolving during continued donepezil hydrochloride treatment without the need for dose modification.
There is evidence to suggest that the frequency of these common adverse reactions may be affected by the rate of titration.
An open-label study was conducted with 269 patients who received placebo in the 15- and 30-week studies.
These patients were titrated to a dose of 10 mg/day over a 6-week period.
The rates of common adverse reactions were lower than those seen in patients titrated to 10 mg/day over one week in the controlled clinical trials and were comparable to those seen in patients on 5 mg/day.
See Table 2 for a comparison of the most common adverse reactions following one and six week titration regimens.
Table 2.
Comparison of Rates of Adverse Reactions in Mild to Moderate Patients Titrated to 10 mg/day over 1 and 6 Weeks No titration One week titration Six week titration Adverse Reaction Placebo (n=315) % 5 mg/day (n=311) % 10 mg/day (n=315) 5 10 mg/day (n=269) % Nausea 6 5 19 6 Diarrhea 5 8 15 9 Insomnia 6 6 14 6 Fatigue 3 4 8 3 Vomiting 3 3 8 5 Muscle cramps 2 6 8 3 Anorexia 2 3 7 3 Table 3 lists adverse reactions that occurred in at least 2% of patients in pooled placebo-controlled trials who received either donepezil hydrochloride 5 mg or 10 mg and for which the rate of occurrence was greater for patients treated with donepezil hydrochloride than with placebo.
In general, adverse reactions occurred more frequently in female patients and with advancing age.
Table 3.
Adverse Reactions in Pooled Placebo-Controlled Clinical Trials in Mild to Moderate Alzheimer’s Disease Adverse Reaction Placebo (n=355) % Donepezil Hydrochloride (n=747) % Percent of Patients with any Adverse Reaction 72 74 Nausea 6 11 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 Arthritis 1 2 Frequent Urination 1 2 Somnolence <1 2 Syncope 1 2 Severe Alzheimer's Disease Severe Alzheimer’s Disease (donepezil hydrochloride 5 mg/day and 10 mg/day) Donepezil hydrochloride has been administered to over 600 patients with severe Alzheimer’s disease during clinical trials of at least 6 months duration, including three double-blind, placebo-controlled trials, two of which had an open label extension. Adverse Reactions Leading to Discontinuation The rates of discontinuation from controlled clinical trials of donepezil hydrochloride due to adverse reactions for the donepezil hydrochloride patients were approximately 12% compared to 7% for placebo patients.
The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of donepezil hydrochloride patients and at twice or more the incidence seen in placebo, were anorexia (2% vs.
1% placebo), nausea (2% vs.
<1% placebo), diarrhea (2% vs.
0% placebo) and urinary tract infection (2% vs.
1% placebo).
Most Common Adverse Reactions The most common adverse reactions, defined as those occurring at a frequency of at least 5% in patients receiving donepezil hydrochloride and at twice or more the placebo rate, are largely predicted by donepezil hydrochloride’s cholinomimetic effects.
These include diarrhea, anorexia, vomiting, nausea, and ecchymosis.
These adverse reactions were often transient, resolving during continued donepezil hydrochloride treatment without the need for dose modification.
Table 4 lists adverse reactions that occurred in at least 2% of patients in pooled placebo-controlled trials who received donepezil hydrochloride 5 mg or 10 mg and for which the rate of occurrence was greater for patients treated with donepezil hydrochloride than with placebo.
Table 4.
Adverse Reactions in Pooled Controlled Clinical Trials in Severe Alzheimer’s Disease Body System/Adverse Reaction Placebo (n=392) % Donepezil Hydrochloride (n=501) % Percent of Patients with any Adverse Reaction 73 81 Accident 12 13 Infection 9 11 Diarrhea 3 4 Anorexia 2 3 Vomiting 2 3 Nausea 1 2 Insomnia <1 2 Ecchymosis 2 3 Headache 1 2 Pain 1 2 Back Pain 4 10 Eczema 4 8 Hallucinations 4 8 Hostility 2 6 Increase in Creatine Phosphokinase 2 5 Nervousness 1 3 Fever 1 2 Chest Pain <1 2 Confusion 4 5 Dehydration 2 3 Depression 2 3 Dizziness 1 3 Emotional Lability 1 2 Hemorrhage 1 2 Hyperlipemia 1 2 Personality Disorder 1 2 Somnolence 1 2 Personality Disorder 1 2 Syncope 2 3 Urinary Incontinence 1 2 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of donepezil hydrochloride.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Abdominal pain, agitation, aggression, cholecystitis, confusion, convulsions, hallucinations, heart block (all types), hemolytic anemia, hepatitis, hyponatremia, neuroleptic malignant syndrome, pancreatitis, rash, rhabdomyolysis, QTc prolongation, and torsade de pointes.