Donepezil
Donepezil hydrochloride · Tablet · Oral
Uses
Donepezil hydrochloride tablets are 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 tablet, 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 ).
Dosage and administration
Mild to Moderate Alzheimer’s Disease: 5 mg to 10 mg once daily ( 2.1 ) Moderate to Severe Alzheimer’s Disease: 10 mg to 23 mg once daily (2.2) 2.1 Dosing in Mild to Moderate Alzheimer's Disease The recommended starting dosage of donepezil hydrochloride tablet is 5 mg administered once per day in the evening, just prior to retiring. The maximum recommended dosage of donepezil hydrochloride tablet in patients with mild to moderate Alzheimer’s disease is 10 mg per day. A dose of 10 mg should not be administered until patients have been on a daily dose of 5 mg for 4 to 6 weeks. 2.2 Dosing in Moderate to Severe Alzheimer’s Disease The recommended starting dosage of donepezil hydrochloride tablet is 5 mg administered once per day in the evening, just prior to retiring. The maximum recommended dosage of donepezil hydrochloride tablet in patients with moderate to severe Alzheimer’s disease is 23 mg per day. A dose of 10 mg should not be administered until patients have been on a daily dose of 5 mg for 4 to 6 weeks. A dose of 23 mg per day should not be administered until patients have been on a daily dose of 10 mg for at least 3 months. 2.3 Administration Information Donepezil hydrochloride tablet should be taken in the evening, just prior to retiring. Donepezil hydrochloride tablet can be taken with or without food.
Dosage forms and strengths
Donepezil hydrochloride tablets, USP are supplied as film-coated, round tablets containing 5 mg, or 10 mg of donepezil hydrochloride. The 5 mg tablets are white round biconvex, film-coated tablets debossed with ‘I’ on one side and ‘24’ on the other side. The 10 mg tablets are yellow round biconvex, film-coated tablets debossed with ‘I’ on one side and ‘21’ on the other side. Tablets: 5 mg and 10 mg ( 3 )
Contraindications
Donepezil hydrochloride tablets are contraindicated in patients with known hypersensitivity to donepezil hydrochloride or to piperidine derivatives. Known hypersensitivity to donepezil hydrochloride or to piperidine derivatives ( 4 )
Warnings and precautions
Cholinesterase inhibitors are likely to exaggerate succinylcholine-type muscle relaxation during anesthesia ( 5.1 ) Cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block ( 5.2 ) Donepezil hydrochloride can cause vomiting. Patients should be observed closely at initiation of treatment and after dose increases ( 5.3 ) Patients should be monitored closely for symptoms of active or occult gastrointestinal (GI) bleeding, especially those at increased risk for developing ulcers ( 5.4 ) The use of donepezil hydrochloride in a dose of 23 mg once daily is associated with weight loss (5.5) Cholinomimetics may cause bladder outflow obstructions ( 5.6 ) Cholinomimetics are believed to have some potential to cause generalized convulsions ( 5.7 ) Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease ( 5.8 ) 5.1 Anesthesia Donepezil hydrochloride, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia. 5.2 Cardiovascular Conditions Because of their pharmacological action, cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes. This effect may manifest as bradycardia or heart block in patients both with and without known underlying cardiac conduction abnormalities. Syncopal episodes have been reported in association with the use of donepezil hydrochloride. 5.3 Nausea and Vomiting Donepezil hydrochloride, as a predictable consequence of its pharmacological properties, has been shown to produce diarrhea, nausea, and vomiting. These effects, when they occur, appear more frequently with the 10 mg/day dose than with the 5 mg/day dose, and more frequently with the 23 mg dose than with the 10 mg dose. Specifically, in a controlled trial that compared a dose of 23 mg/day to 10 mg/day in patients who had been treated with donepezil 10 mg/day for at least three months, the incidence of nausea in the 23 mg group was markedly greater than in the patients who continued on 10 mg/day (11.8% vs. 3.4%, respectively), and the incidence of vomiting in the 23 mg group was markedly greater than in the 10 mg group (9.2% vs. 2.5%, respectively). The percent of patients who discontinued treatment due to vomiting in the 23 mg group was markedly higher than in the 10 mg group (2.9% vs. 0.4%, respectively). Although in most cases, these effects have been transient, sometimes lasting one to three weeks, and have resolved during continued use of donepezil hydrochloride, patients should be observed closely at the initiation of treatment and after dose increases. 5.4 Peptic Ulcer Disease and GI Bleeding Through their primary action, cholinesterase inhibitors may be expected to increase gastric acid secretion due to increased cholinergic activity. Therefore, patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical studies of donepezil hydrochloride in a dose of 5 mg/day to 10 mg/day have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. Results of a controlled clinical study with 23 mg/day showed an increase, relative to 10 mg/day, in the incidence of peptic ulcer disease (0.4% vs. 0.2%) and gastrointestinal bleeding from any site (1.1% vs. 0.6%). 5.5 Weight Loss Weight loss was reported as an adverse reaction in 4.7% of patients assigned to donepezil hydrochloride in a dose of 23 mg/day compared to 2.5% of patients assigned to 10 mg/day. Compared to their baseline weights, 8.4% of patients taking 23 mg/day were found to have a weight decrease of ≥ 7% by the end of the study, while 4.9% of patients taking 10 mg/day were found to have weight loss of ≥ 7% at the end of the study. 5.6 Genitourinary Conditions Although not observed in clinical trials of donepezil hydrochloride, cholinomimetics may cause bladder outflow obstruction. 5.7 Neurological Conditions: Seizures Cholinomimetics are believed to have some potential to cause generalized convulsions. However, seizure activity also may be a manifestation of Alzheimer’s disease. 5.8 Pulmonary Conditions Because of their cholinomimetic actions, cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
Side effects
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 )] Weight Loss [see Warnings and Precautions (5.5) ] 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 Quallent Pharmaceuticals Health LLC 1-877-605-7243 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) % 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 (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).
Drug interactions
Cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications ( 7.1 ) A synergistic effect may be expected with concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists ( 7.2 ) 7.1 Use with Anticholinergics Because of their mechanism of action, cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications. 7.2 Use with Cholinomimetics and Other Cholinesterase Inhibitors A synergistic effect may be expected when cholinesterase inhibitors are given concurrently with succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists such as bethanechol.
Use in specific populations
Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ). 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risks associated with the use of donepezil hydrochloride in pregnant women. In animal studies, developmental toxicity was not observed when donepezil was administered to pregnant rats and rabbits during organogenesis, but administration to rats during the latter part of pregnancy and throughout lactation resulted in increased stillbirths and decreased offspring survival at clinically relevant doses [ see Data ]. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. The background risks of major birth defects and miscarriage for the indicated population are unknown. Data Animal Data Oral administration of donepezil to pregnant rats and rabbits during the period of organogenesis did not produce any teratogenic effects at doses up to 16 mg/kg/day (approximately 6 times the maximum recommended human dose [MRHD] of 23 mg/day on a mg/m 2 basis) and 10 mg/kg/day (approximately 7 times the MRHD on a mg/m 2 basis), respectively. Oral administration of donepezil (1, 3, 10 mg/kg/day) to rats during late gestation and throughout lactation to weaning produced an increase in stillbirths and reduced offspring survival through postpartum day 4 at the highest dose. The no-effect dose of 3 mg/kg/day is approximately equal to the MRHD on a mg/m 2 basis. 8.2 Lactation Risk Summary There are no data on the presence of donepezil or its metabolites in human milk, the effects on the breastfed infant, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for donepezil hydrochloride and any potential adverse effects on the breastfed infant from donepezil hydrochloride or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Alzheimer’s disease is a disorder occurring primarily in individuals over 55 years of age. The mean age of patients enrolled in the clinical studies with donepezil hydrochloride was 73 years; 80% of these patients were between 65 and 84 years old, and 49% of patients were at or above the age of 75. The efficacy and safety data presented in the clinical trials section were obtained from these patients. There were no clinically significant differences in most adverse reactions reported by patient groups ≥ 65 years old and < 65 years old. 8.6 Lower Weight Individuals In the controlled clinical trial, among patients in the donepezil hydrochloride 23 mg treatment group, those patients weighing < 55 kg reported more nausea, vomiting, and decreased weight than patients weighing 55 kg or more. There were more withdrawals due to adverse reactions as well. This finding may be related to higher plasma exposure associated with lower weight.
Pregnancy
8.1 Pregnancy Risk Summary There are no adequate data on the developmental risks associated with the use of donepezil hydrochloride in pregnant women. In animal studies, developmental toxicity was not observed when donepezil was administered to pregnant rats and rabbits during organogenesis, but administration to rats during the latter part of pregnancy and throughout lactation resulted in increased stillbirths and decreased offspring survival at clinically relevant doses [ see Data ]. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. The background risks of major birth defects and miscarriage for the indicated population are unknown. Data Animal Data Oral administration of donepezil to pregnant rats and rabbits during the period of organogenesis did not produce any teratogenic effects at doses up to 16 mg/kg/day (approximately 6 times the maximum recommended human dose [MRHD] of 23 mg/day on a mg/m 2 basis) and 10 mg/kg/day (approximately 7 times the MRHD on a mg/m 2 basis), respectively. Oral administration of donepezil (1, 3, 10 mg/kg/day) to rats during late gestation and throughout lactation to weaning produced an increase in stillbirths and reduced offspring survival through postpartum day 4 at the highest dose. The no-effect dose of 3 mg/kg/day is approximately equal to the MRHD on a mg/m 2 basis.
Overdosage
Because strategies for the management of overdose are continually evolving, it is advisable to contact a Poison Control Center to determine the latest recommendations for the management of an overdose of any drug. As in any case of overdose, general supportive measures should be utilized. Overdosage with cholinesterase inhibitors can result in cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Tertiary anticholinergics such as atropine may be used as an antidote for donepezil hydrochloride overdosage. Intravenous atropine sulfate titrated to effect is recommended: an initial dose of 1.0 to 2.0 mg IV with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when co-administered with quaternary anticholinergics such as glycopyrrolate. It is not known whether donepezil hydrochloride and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration). Dose-related signs of toxicity in animals included reduced spontaneous movement, prone position, staggering gait, lacrimation, clonic convulsions, depressed respiration, salivation, miosis, tremors, fasciculation, and lower body surface temperature.
Description
Donepezil hydrochloride USP is a reversible inhibitor of the enzyme acetylcholinesterase, known chemically as 2, 3-Dihydro-5, 6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1 H -inden-1-one hydrochloride. Donepezil hydrochloride USP is commonly referred to in the pharmacological literature as E2020. It has an empirical formula of C 24 H 29 NO 3 HCl and a molecular weight of 415.96. Donepezil hydrochloride USP is a white to off white crystalline powder and is soluble in water, methanol and chloroform and sparingly soluble in acetic acid. Donepezil hydrochloride USP is available for oral administration in film-coated tablets containing 5 and 10 mg of donepezil hydrochloride USP. Inactive ingredients in 5 mg and 10 mg tablets are corn starch, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate and microcrystalline cellulose. The film coating contains hypromellose, polyethylene glycol, talc and titanium dioxide. Additionally, the 10 mg tablet contains yellow iron oxide as a coloring agent. Meets Organic Impurities Test Procedure 2 donepezilchemicalstructure
Mechanism of action
12.1 Mechanism of Action Current theories on the pathogenesis of the cognitive signs and symptoms of Alzheimer’s disease attribute some of them to a deficiency of cholinergic neurotransmission. Donepezil hydrochloride is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. There is no evidence that donepezil alters the course of the underlying dementing process.
How supplied
16.1 Donepezil Hydrochloride Tablets, USP Donepezil hydrochloride tablets USP, 5 mg are white round biconvex, film coated tablets debossed with ‘I’ on one side and ‘24’ on the other side. They are supplied as follows Bottles of 500 NDC 82009-119-05 Bottles of 1000 NDC 82009-119-10 Donepezil hydrochloride tablets USP, 10 mg are yellow round biconvex, film coated tablets debossed with ‘I’ on one side and ‘21’ on the other side. They are supplied as follows Bottles of 500 NDC 82009-120-05 Bottles of 1000 NDC 82009-120-10 Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Instruct patients and caregivers to take donepezil hydrochloride tablets only once per day, as prescribed. Instruct patients and caregivers that donepezil hydrochloride tablets can be taken with or without food. Advise patients and caregivers that donepezil hydrochloride tablets may cause nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and decreased appetite. Advise patients to notify their healthcare provider if they are pregnant or plan to become pregnant. Manufactured for: Quallent Pharmaceuticals Health LLC Grand Cayman, Cayman Islands By: HETERO TM Hetero Labs Limited, Unit V, Polepally, Jadcherla, Mahabubnagar - 509 301, India. Revised: 02/2025 donepezillogo
Label text from the FDA structured product label by Quallent Pharmaceuticals Health LLC (revised Dec 5, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Donepezil Hydrochloride in 8 products
Donepezil NDC products (8)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-2627 | Donepezil Hydrochloride 10 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 60687-292 | Donepezil Hydrochloride 5 mg/1 Tablet | American Health Packaging | ANDA |
| 60687-303 | Donepezil Hydrochloride 10 mg/1 Tablet | American Health Packaging | ANDA |
| 31722-737 | Donepezil Hydrochloride 5 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-738 | Donepezil Hydrochloride 10 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 82009-119 | Donepezil Hydrochloride 5 mg/1 Tablet | Quallent Pharmaceuticals Health LLC | ANDA |
| 82009-120 | Donepezil Hydrochloride 10 mg/1 Tablet | Quallent Pharmaceuticals Health LLC | ANDA |
| 70518-4380 | Donepezil Hydrochloride 5 mg/1 Tablet | REMEDYREPACK INC. | ANDA |
Frequently asked questions
What is Donepezil used for?
Donepezil hydrochloride tablets are 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 tablet, 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…
What are the side effects of Donepezil?
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 )] Weight Loss [see Warnings and Precautions (5.5) ] Genitourinary Conditions [see Warnings and Precautions (… See the full label for the complete list.
Who makes Donepezil?
Donepezil is listed by 5 labelers in the FDA NDC directory, including A-S Medication Solutions, American Health Packaging, Camber Pharmaceuticals, Inc., Quallent Pharmaceuticals Health LLC.