Donepezil Hydrochloride 5 mg Tablet, Film Coated, 30-count — NDC 46708-295-30 (Billing 46708-0295-30)
This is a package of 30 tablets of Donepezil Hydrochloride 5 mg Tablet, Film Coated from Alembic Pharmaceuticals Limited, marketed since Jan 2016 and currently FDA-listed.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
- RxCUI (RxNorm): 997223
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Cholinesterase Inhibitor class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Donepezil is used to treat Alzheimer's disease (AD; a brain disease that affects memory, thinking, and behavior). Donepezil is in a class of medications called cholinesterase inhibitors. It works by increasing the amount of a certain naturally occurring substance in the brain that play a role in mental function.
Read the full MedlinePlus article ↗- Unfortunately, no — donepezil doesn't cure Alzheimer's disease, and it won't stop the disease from progressing over time. What it can do is help manage symptoms like memory and thi...
- Will donepezil cure my family member's Alzheimer's disease?
- You should take donepezil once a day in the evening, just before going to bed. Food doesn't affect how well it's absorbed, so you can take it with or without a meal — whatever work...
- When should I take donepezil, and does it matter if I take it with food?
Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $0.1339 | $4.02 / 30 tablets |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · refreshed Oct 3, 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 46708-0295-10 46708-295-10 Main listing | 100 TABLET, FILM COATED in 1 CARTON | 2016-01-29 | — | Active |
| 46708-0295-30 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE | 2016-01-29 | — | Active |
| 46708-0295-90 46708-295-90 | 90 TABLET, FILM COATED in 1 BOTTLE | 2016-01-29 | — | Active |
| 46708-0295-91 46708-295-91 | 1000 TABLET, FILM COATED in 1 BOTTLE | 2016-01-29 | — | Active |
You're viewing the smallest of 4 pack sizes for this product.
Pack size FAQ
What quantity is in this package?
How does this package differ from NDC 46708-0295-90?
What NDC number is used to bill for this package of Donepezil Hydrochloride 5 mg Tablet, Film Coated?
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Donepezil hydrochloride 5 mg 55111-0356-05 | Dr. | 500 tablets | $0.044 | AB | Discontinued | — |
| Donepezil Hydrochloride 5 mg 00904-6477-61 | Major | 1 tablet | $0.044 | AB | Availability likely | — |
| Donepezil Hydrochloride 5 mg 16571-0778-03 | Rising | 30 tablets | $0.044 | AB | Availability likely | — |
| Donepezil Hydrochloride 5 mg 33342-0027-07 | Macleods | 30 tablets | $0.044 | AB | Availability likely | — |
| donepezil hydrochloride 5 mg 43547-0275-03 | Solco | 30 tablets | $0.044 | AB | Availability likely | — |
| Donepezil 5 mg 60687-0292-01 | American | 100 tablets | $0.044 | AB | Availability likely | — |
| Donepezil Hydrochloride 5 mg 71093-0127-01 | ACI | 30 tablets | $0.044 | — | Discontinued | — |
| Donepezil 5 mg 82009-0119-05 | Quallent | 500 tablets | $0.044 | AB | Availability likely | — |
| Donepezil Hydrochloride 5 mg 00615-7951-05 | NCS | 15 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 13668-0102-05 | Torrent | 500 tablets | — | AB | FDA listed | — |
| donepezil hydrochloride 5 mg 29300-0248-01 | Unichem | 100 tablets | — | — | FDA listed | — |
| Donepezil 5 mg 31722-0737-01 | Camber | 100 tablets | — | AB | FDA listed | — |
| donepezil hydrochloride 5 mg 43547-0878-03 | Solco | 30 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mgthis 46708-0295-30 | Alembic | 30 tablets | — | AB | FDA listed | — |
| donepezil hydrochloride 5 mg 50090-3537-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 50090-6329-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 50090-7365-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 50228-0139-10 | ScieGen | 1000 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 55154-7883-00 | Cardinal | 1 tablet | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 60429-0321-10 | Golden | 1000 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 62332-0092-10 | Alembic | 100 tablets | — | AB | FDA listed | — |
| Aricept 5 mg 62856-0245-30 | Eisai | 30 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 63629-9326-01 | Bryant | 90 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 65862-0325-01 | Aurobindo | 100 tablets | — | — | FDA listed | — |
| Donepezil Hydrochloride 5 mg 67046-1476-03 | Coupler | 30 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 68788-8208-03 | Preferred | 30 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 68788-8711-03 | Preferred | 30 tablets | — | — | FDA listed | — |
| Donepezil 5 mg 70518-4380-00 | REMEDYREPACK | 90 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 70518-4392-00 | REMEDYREPACK | 90 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 71209-0019-01 | Cadila | 30 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 71335-2022-01 | Bryant | 90 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 71335-2065-01 | Bryant | 90 tablets | — | — | Discontinued | — |
| Donepezil Hydrochloride 5 mg 71335-2093-01 | Bryant | 90 tablets | — | AB | FDA listed | — |
| Donepezil Hydrochloride 5 mg 72162-2136-00 | Bryant | 1000 tablets | — | — | Discontinued | — |
| Donepezil Hydrochloride 5 mg 72189-0031-90 | Direct_Rx | 90 tablets | — | AB | Discontinued | — |
| donepezil hydrochloride 5 mg 87063-0305-01 | ASCLEMED | 100 tablets | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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Hydroxypropyl cellulose is a plant-derived thickener and binder made from cellulose. In medicines, it helps hold tablet ingredients together, thickens liquids, and can form a coating on pills or capsules.
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Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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Polyethylene glycol 6000 is a synthetic polymer made from ethylene glycol units. It acts as a binder, filler, and solubilizer in medicines to help hold ingredients together, add bulk, and improve how well active drugs dissolve and absorb.
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A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
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A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
9 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
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Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and 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).
⏱️ Dosage and Administration ▾
2. DOSAGE AND ADMINISTRATION •Mild to Moderate Alzheimer’s Disease - 5 mg or 10 mg once daily (2.1) •Moderate to Severe Alzheimer’s Disease - 10 mg once daily (2.2) 2.1. Dosing in Mild to Moderate Alzheimer's Disease The recommended starting dosage of donepezil hydrochloride is 5 mg administered once per day in the evening, just prior to retiring.
The maximum recommended dosage of donepezil hydrochloride 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 is 5 mg administered once per day in the evening, just prior to retiring. 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. 2.3.
Administration Information Donepezil hydrochloride tablets should be taken in the evening, just prior to retiring. Donepezil hydrochloride tablets can be taken with or without food.
💊 Dosage Forms and Strengths ▾
3. DOSAGE FORMS AND STRENGTHS Donepezil hydrochloride tablets, USP are supplied as film-coated, round tablets containing 5 mg or 10 mg of donepezil hydrochloride USP. The 5 mg tablets are white to off white. The tablet is debossedwith 'L160' on one side and plain on other side. The 10 mg tablets are yellow. The tablet is debossedwith 'L161' on one side and plain on other side. Tablets: 5 mg and 10 mg (3)
⛔ Contraindications ▾
4. CONTRAINDICATIONS Donepezil hydrochlorideis 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 Cautions ▾
5. 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 bleeding (GI), especially those at increased risk for developing ulcers (5.4).
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.
Although in most cases, these effects have been mild and 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 hydrochloridein 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. 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.
🤒 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)] 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 Alembic Pharmaceuticals Limited at 1-866 210 9797 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 1,200 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 events 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 Group 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… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7. DRUG INTERACTIONS Cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications (7.2). A synergistic effect may be expected with concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists (7.3).
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 ▾
8. USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, donepezil hydrochloride may cause fetal harm (8.1). 8.1.
Pregnancy Pregnancy Category C There are no adequate or well-controlled studies in pregnant women. Donepezil hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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 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. 8.3.
Nursing Mothers It is not known whether donepezil is excreted in human milk. Caution should be exercised when donepezil hydrochloride is administered to a nursing woman. 8.4.
Pediatric Use The safety and effectiveness of donepezil hydrochloride in children 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.
🤰 Pregnancy ▾
8.1. Pregnancy Pregnancy Category C There are no adequate or well-controlled studies in pregnant women. Donepezil hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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 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.
🧒 Pediatric Use ▾
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.
🆘 Overdosage ▾
10. 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 to 2 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.
🧬 Clinical Pharmacology ▾
12. CLINICAL PHARMACOLOGY 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.
12.2. Pharmacokinetics Pharmacokinetics of donepezil are linear over a dose range of 1 to 10 mg given once daily. The rate and extent of absorption of donepezil hydrochloridetablets are not influenced by food.
The elimination half life of donepezil is about 70 hours, and the mean apparent plasma clearance (Cl/F) is 0.13 to
0.19L/hr/kg. Following multiple dose administration, donepezil accumulates in plasma by 4 to 7 fold, and steady state is reached within 15 days. The steady state volume of distribution is 12 to 16 L/kg.
Donepezil is approximately 96% bound to human plasma proteins, mainly to albumins (about 75%) and alpha 1 - acid glycoprotein (about 21%) over the concentration range of 2 to 1000 ng/mL. Donepezil is both excreted in the urine intact and extensively metabolized to four major metabolites, two of which are known to be active, and a number of minor metabolites, not all of which have been identified. Donepezil is metabolized by CYP 450 isoenzymes 2D6 and 3A4 and undergoes glucuronidation.
Following administration of 14 C-labeled donepezil, plasma radioactivity, expressed as a percent of the administered dose, was present primarily as intact donepezil (53%) and as 6-O-desmethyl donepezil (11%), which has been reported to inhibit AChE to the same extent as donepezil in vitro and was found in plasma at concentrations equal to about 20% of donepezil. Approximately 57% and 15% of the total radioactivity was recovered in urine and feces, respectively, over a period of 10 days, while 28% remained unrecovered, with about 17% of the donepezil dose recovered in the urine as unchanged drug.
Examination of the effect of CYP2D6 genotype in Alzheimer’s patients showed differences in clearance values among CYP2D6 genotype subgroups. When compared to the extensive metabolizers, poor metabolizers had a 31.5% slower clearance and ultra-rapid metabolizers had a 24% faster clearance. Hepatic Disease In a study of 10 patients with stable alcoholic cirrhosis, the clearance of donepezil hydrochloride was decreased by 20% relative to 10 healthy age- and sex-matched subjects.
Renal Disease In a study of 11 patients with moderate to severe renal impairment (Cl C < 18 mL/min/1.73 m 2 ) the clearance of donepezil hydrochloride did not differ from 11 age- and sex-matched healthy subjects. Age No formal pharmacokinetic study was conducted to examine age-related differences in the pharmacokinetics of donepezil hydrochloride. Population pharmacokinetic analysis suggested that the clearance of donepezil in patients decreases with increasing age.
When compared with 65-year old, subjects, 90-year old subjects have a 17% decrease in clearance, while 40-year old subjects have a 33% increase in clearance. The effect of age on donepezil clearance may not be clinically significant. Gender and Race No specific pharmacokinetic study was conducted to investigate the effects of gender and race on the disposition of donepezil hydrochloride.
However, retrospective pharmacokinetic analysis and population pharmacokinetic analysis of plasma donepezil concentrations measured in patients with Alzheimer’s disease indicates that gender and race (Japanese and Caucasians) did not affect the clearance of donepezil hydrochloride to an important degree. Body Weight There was a relationship noted between body weight and clearance. Over the range of body weight from 50 kg to 110 kg, clearance increased from
7.77L/h to 14… [Excerpted — this section continues on DailyMed.]
🧬 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 / Storage and Handling ▾
16. HOW SUPPLIED/STORAGE AND HANDLING 16.1. Donepezil Hydrochloride Tablets, USP Supplied as film-coated, round tablets containing either 5 mg or 10 mg of donepezil hydrochloride USP.
The 5 mg tablets are white to off white. The tablet is debossed with 'L160' on one side and plain on other side. NDC 46708-295-30 bottle of 30 tablets NDC 46708-295-90 bottle of 90 tablets NDC 46708-295-91 bottle of 1000 tablets NDC 46708-295-10 100 (10 x 10) tablets Unit dose blisters The 10 mg tablets are yellow.
The tablet is debossed with 'L161' on one side and plain on other side. NDC 46708-296-30 bottle of 30 tablets NDC 46708-296-90 bottle of 90 tablets NDC 46708-296-91 bottle of 1000 tablets NDC 46708-296-10 100 (10 x 10) tablets Unit dose blisters Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]
📋 Description ▾
11. DESCRIPTION Donepezil hydrochloride 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 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 is a white crystalline powder and is freely soluble in chloroform, soluble in water and in glacial acetic acid, slightly soluble in ethanol and in acetonitrile and practically insoluble in ethyl acetate and in n-hexane. Donepezil hydrochloride tablets, USP are available for oral administration in film-coated tablets containing 5, or 10 mg of donepezil hydrochloride USP .
Inactive ingredients are lactose monohydrate, corn starch, microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate. The film coating contains talc, polyethylene glycol, hypromellose and titanium dioxide. Additionally, the 10 mg tablet contains iron oxide yellow as a coloring agent.
Structure
💬 Information for Patients ▾
17. PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Instruct patients and caregivers to take donepezil hydrochloride tablet 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. Manufactured by: Alembic Pharmaceuticals Limited (Formulation Division), Village Panelav, P.
O. Tajpura, Near Baska, Taluka-Halol, Panchmahal 389350, Gujarat, India. Revised : 11/2015 Patient Package Insert Donepezil Hydrochloride (doe-NEP-e-zil HYE-droe-KLOR-ide) Tablets, USP •Tablets: 5 mg and 10 mg Read the Patient Information that comes with donepezil hydrochloride before the patient starts taking it and each time you get a refill.
There may be new information. This leaflet does not take the place of talking with the doctor about Alzheimer’s disease or treatment for it. If you have questions, ask the doctor or pharmacist.
What is donepezil hydrochloride? Donepezil hydrochloride comes as donepezil hydrochloride film-coated tablets in dosage strengths of 5 mg and 10 mg. Donepezil hydrochloride is a prescription medicine to treat mild, moderate, and severe Alzheimer’s disease.
Donepezil hydrochloride can help with mental function and with doing daily tasks. Donepezil hydrochloride does not work the same in all people. Some people may: •Seem much better •Get better in small ways or stay the same •Get worse over time but slower than expected •Not change and then get worse as expected Donepezil hydrochloride does not cure Alzheimer’s disease.
All patients with Alzheimer’s disease get worse over time, even if they take donepezil hydrochloride. Donepezil hydrochloride has not been approved as a treatment for any medical condition in children. Who should not take donepezil hydrochloride?
The patient should not take donepezil hydrochloride if allergic to any of the ingredients in donepezil hydrochloride or to medicines that contain piperidines. Ask the patient’s doctor if you are not sure. See the end of this leaflet for a list of ingredients in donepezil hydrochloride.
What should I tell the doctor before the patient takes donepezil hydrochloride? Tell the doctor about all the patient’s present or past health problems. Include: •Any heart problems including problems with irregular, slow, or fast heartbeats •Asthma or lung problems •A seizure •Stomach ulcers •Difficulty passing urine •Liver or kidney problems •Trouble swallowing tablets •Present pregnancy or plans to become pregnant.
It is not known if donepezil hydrochloride can harm an unborn baby. •Present breast-feeding. It is not known if donepezil hydrochloride passes into breast milk. Donepezil hydrochloride is not for women who are breast-feeding.
Tell the doctor about all the medicines the patient takes, including prescription and non-prescription medicines, vitamins, and herbal products. Donepezil hydrochloride and other medicines may affect each other. Be particularly sure to tell the doctor if the patient takes aspirin or medicines called nonsteroidal anti-inflammatory drugs (NSAIDs).
There are many NSAID medicines, both prescription and non-prescription. Ask the doctor or pharmacist if you are not sure if any of the patient’s medicines are NSAIDs. Taking NSAIDs and donepezil hydrochloride together may make the patient more likely to get stomach ulcers.
Donepezil hydrochloride taken with certain medicines used for anesthesia may cause side effects. Tell the responsible doctor or dentist that the patient takes donepezil hydrochloride before the patient has: •surgery •medical procedures •dental surgery or procedures. Know the medicines that the patient takes.
Keep a list of all the patient’s medicines. Show it to the doctor or pharmacist before the patient starts a new medicine. How shoul… [Excerpted — this section continues on DailyMed.]
🍼 Nursing Mothers ▾
8.4. Pediatric Use The safety and effectiveness of donepezil hydrochloride in children have not been established.
🧬 Pharmacodynamics ▾
12.2. Pharmacokinetics Pharmacokinetics of donepezil are linear over a dose range of 1 to 10 mg given once daily. The rate and extent of absorption of donepezil hydrochloridetablets are not influenced by food. The elimination half life of donepezil is about 70 hours, and the mean apparent plasma clearance (Cl/F) is 0.13 to
0.19L/hr/kg. Following multiple dose administration, donepezil accumulates in plasma by 4 to 7 fold, and steady state is reached within 15 days. The steady state volume of distribution is 12 to 16 L/kg.
Donepezil is approximately 96% bound to human plasma proteins, mainly to albumins (about 75%) and alpha 1 - acid glycoprotein (about 21%) over the concentration range of 2 to 1000 ng/mL. Donepezil is both excreted in the urine intact and extensively metabolized to four major metabolites, two of which are known to be active, and a number of minor metabolites, not all of which have been identified. Donepezil is metabolized by CYP 450 isoenzymes 2D6 and 3A4 and undergoes glucuronidation.
Following administration of 14 C-labeled donepezil, plasma radioactivity, expressed as a percent of the administered dose, was present primarily as intact donepezil (53%) and as 6-O-desmethyl donepezil (11%), which has been reported to inhibit AChE to the same extent as donepezil in vitro and was found in plasma at concentrations equal to about 20% of donepezil. Approximately 57% and 15% of the total radioactivity was recovered in urine and feces, respectively, over a period of 10 days, while 28% remained unrecovered, with about 17% of the donepezil dose recovered in the urine as unchanged drug.
Examination of the effect of CYP2D6 genotype in Alzheimer’s patients showed differences in clearance values among CYP2D6 genotype subgroups. When compared to the extensive metabolizers, poor metabolizers had a 31.5% slower clearance and ultra-rapid metabolizers had a 24% faster clearance. Hepatic Disease In a study of 10 patients with stable alcoholic cirrhosis, the clearance of donepezil hydrochloride was decreased by 20% relative to 10 healthy age- and sex-matched subjects.
Renal Disease In a study of 11 patients with moderate to severe renal impairment (Cl C < 18 mL/min/1.73 m 2 ) the clearance of donepezil hydrochloride did not differ from 11 age- and sex-matched healthy subjects. Age No formal pharmacokinetic study was conducted to examine age-related differences in the pharmacokinetics of donepezil hydrochloride. Population pharmacokinetic analysis suggested that the clearance of donepezil in patients decreases with increasing age.
When compared with 65-year old, subjects, 90-year old subjects have a 17% decrease in clearance, while 40-year old subjects have a 33% increase in clearance. The effect of age on donepezil clearance may not be clinically significant. Gender and Race No specific pharmacokinetic study was conducted to investigate the effects of gender and race on the disposition of donepezil hydrochloride.
However, retrospective pharmacokinetic analysis and population pharmacokinetic analysis of plasma donepezil concentrations measured in patients with Alzheimer’s disease indicates that gender and race (Japanese and Caucasians) did not affect the clearance of donepezil hydrochloride to an important degree. Body Weight There was a relationship noted between body weight and clearance. Over the range of body weight from 50 kg to 110 kg, clearance increased from
7.77 L/h to
14.04L/h, with a value of 10 L/hr for 70 kg individuals. Drug Interactions Effect of Donepezil Hydrochloride on the Metabolism of Other Drugs No in vivo clinical trials have investigated the effect of donepezil hydrochloride on the clearance of drugs metabolized by CYP 3A4 (e.g., cisapride, terfenadine) or by CYP 2D6 (e.g., imipramine). However, in vitro studies show a low rate of binding to these enzymes (mean K i about 50 to 130 µM), that, given the therapeutic plasma concentrations of donepezil (164 nM), indicates little likelihood of interference.
Bas… [Excerpted — this section continues on DailyMed.]
🔬 Clinical Studies ▾
14. CLINICAL STUDIES 14.1. Mild to Moderate Alzheimer's Disease The effectiveness of donepezil hydrochloride as a treatment for mild to moderate Alzheimer’s disease is demonstrated by the results of two randomized, double-blind, placebo-controlled clinical investigations in patients with Alzheimer’s disease (diagnosed by NINCDS and DSM III-R criteria, Mini-Mental State Examination ≥ 10 and ≤ 26 and Clinical Dementia Rating of 1 or 2).
The mean age of patients participating in donepezil hydrochloride trials was 73 years with a range of 50 to 94. Approximately 62% of patients were women and 38% were men. The racial distribution was white 95%, black 3% and other races 2%.
The higher dose of 10 mg did not provide a statistically significantly greater clinical benefit than 5 mg. There is a suggestion, however, based upon order of group mean scores and dose trend analyses of data from these clinical trials, that a daily dose of 10 mg of donepezil hydrochloride might provide additional benefit for some patients. Accordingly, whether or not to employ a dose of 10 mg is a matter of prescriber and patient preference.
Study Outcome Measures In each study, the effectiveness of treatment with donepezil hydrochloride was evaluated using a dual outcome assessment strategy. The ability of donepezil hydrochloride to improve cognitive performance was assessed with the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), a multi-item instrument that has been extensively validated in longitudinal cohorts of Alzheimer’s disease patients. The ADAS-cog examines selected aspects of cognitive performance including elements of memory, orientation, attention, reasoning, language and praxis.
The ADAS-cog scoring range is from 0 to 70, with higher scores indicating greater cognitive impairment. Elderly normal adults may score as low as 0 or 1, but it is not unusual for non-demented adults to score slightly higher. The patients recruited as participants in each study had mean scores on the ADAS-cog of approximately 26 points, with a range from 4 to 61.
Experience based on longitudinal studies of ambulatory patients with mild to moderate Alzheimer’s disease suggest that scores on the ADAS-cog increase (worsen) by 6 to 12 points per year. However, smaller changes may be seen in patients with very mild or very advanced disease since the ADAS-cog is not uniformly sensitive to change over the course of the disease. The annualized rate of decline in the placebo patients participating in donepezil hydrochloride trials was approximately 2 to 4 points per year.
The ability of donepezil hydrochloride to produce an overall clinical effect was assessed using a Clinician’s Interview-Based Impression of Change that required the use of caregiver information, the CIBIC-plus. The CIBIC-plus is not a single instrument and is not a standardized instrument like the ADAS-cog. Clinical trials for investigational drugs have used a variety of CIBIC formats, each different in terms of depth and structure.
As such, results from a CIBIC-plus reflect clinical experience from the trial or trials in which it was used and cannot be compared directly with the results of CIBIC-plus evaluations from other clinical trials. The CIBIC-plus used in donepezil hydrochloride trials was a semi-structured instrument that was intended to examine four major areas of patient function: General, Cognitive, Behavioral and Activities of Daily Living. It represents the assessment of a skilled clinician based upon his/her observations at an interview with the patient, in combination with information supplied by a caregiver familiar with the behavior of the patient over the interval rated.
The CIBIC-plus is scored as a seven point categorical rating, ranging from a score of 1, indicating “markedly improved,” to a score of 4, indicating “no change” to a score of 7, indicating “markedly worse”. The CIBIC-plus has not been systematically compared directly to assessments not using informati… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13. NONCLINICAL TOXICOLOGY 13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility No evidence of a carcinogenic potential was obtained in an 88-week carcinogenicity study of donepezil conducted in mice at oral doses up to 180 mg/kg/day, or in a 104-week carcinogenicity study in rats at oral doses up to 30 mg/kg/day (approximately 13 times the MRHD on a mg/m 2 basis).
Donepezil was negative in a battery of genotoxicity assays ( in vitro bacterial reverse mutation, in vitro mouse lymphoma tk , in vitro chromosomal aberration, and in vivo mouse micronucleus). Donepezil had no effect on fertility in rats at oral doses up to 10 mg/kg/day (approximately 4 times the MRHD on a mg/m 2 basis) when administered to males and females prior to and during mating and continuing in females through implantation. 13.2.
Animal Toxicology and/or Pharmacology In an acute dose neurotoxicity study in female rats, oral administration of donepezil and memantine in combination resulted in increased incidence, severity, and distribution of neurodegeneration compared with memantine alone. The no-effect levels of the combination were associated with clinically relevant plasma donepezil and memantine levels. The relevance of this finding to humans is unknown.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility No evidence of a carcinogenic potential was obtained in an 88-week carcinogenicity study of donepezil conducted in mice at oral doses up to 180 mg/kg/day, or in a 104-week carcinogenicity study in rats at oral doses up to 30 mg/kg/day (approximately 13 times the MRHD on a mg/m 2 basis). Donepezil was negative in a battery of genotoxicity assays ( in vitro bacterial reverse mutation, in vitro mouse lymphoma tk , in vitro chromosomal aberration, and in vivo mouse micronucleus).
Donepezil had no effect on fertility in rats at oral doses up to 10 mg/kg/day (approximately 4 times the MRHD on a mg/m 2 basis) when administered to males and females prior to and during mating and continuing in females through implantation.
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 5 mg Donepezil Hydrochloride Tablets, USP 5 mg (30 Tablets in 1 Bottle) Each film-coated tablet contains 5 mg donepezil hydrochloride USP. 46708-295-30 donepezil-5mg.jpg
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 10 mg Donepezil Hydrochloride Tablets, USP 10 mg (30 Tablets in 1 Bottle) Each film-coated tablet contains 10 mg donepezil hydrochloride USP. 46708-296-30 10 mg 30's bottle pack
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