Donepezil Hydrochloride

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

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.

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Donepezil hydrochloride tablets, USP are 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, round, biconvex, film-coated tablets debossed with ‘ML 89’ on one side and plain on the other side. • The 10 mg tablets are yellow, round, biconvex, film-coated tablets debossed with ‘ML 88’ on one side and plain on the other side. Donepezil hydrochloride 23 mg tablets are supplied as film-coated, round tablets containing 23 mg of donepezil hydrochloride USP. • The 23 mg tablets are red, round, biconvex, film-coated tablets debossed with “C 26” on one side, and plain on the other side. Donepezil hydrochloride orally disintegrating tablets, USP are supplied as round tablets containing either 5 mg or 10 mg of donepezil hydrochloride USP. • The 5 mg orally disintegrating tablets are yellow, circular, flat face, beveled edge uncoated tablets debossed with “CL 31” on one side and plain on the other side. • The 10 mg orally disintegrating tablets are yellow, circular, flat face, beveled edge uncoated tablets debossed with “CL 32” on one side and plain on the other side.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

Donepezil hydrochloride is contraindicated in patients with known hypersensitivity to donepezil hydrochloride or to piperidine derivatives.

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

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 )]

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

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.

11 DESCRIPTION

DESCRIPTION SECTION

Donepezil hydrochloride, USP are 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 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 USP is available for oral administration in film-coated tablets containing 5, 10, or 23 mg of donepezil hydrochloride. Inactive ingredients in 5 mg and 10 mg tablets are lactose monohydrate, pregelatinised starch, microcrystalline cellulose, colloidal silicon dioxide and magnesium stearate. The film coating contains talc, propylene glycol, hypromellose and titanium dioxide. Additionally, the 10 mg tablet contains yellow iron oxide (synthetic) as a coloring agent. Inactive ingredients in 23 mg tablets include hydroxypropyl cellulose, lactose monohydrate, magnesium stearate and hypromellose. The film coating includes ferric oxide red, hypromellose, polyethylene glycol, talc and titanium dioxide. USP Dissolution Test pending. Donepezil hydrochloride orally disintegrating tablets USP are available for oral administration. Each donepezil hydrochloride orally disintegrating tablets contains 5 or 10 mg of donepezil hydrochloride USP. Inactive ingredients are mannitol, crospovidone, sucralose, sodium chloride, ferric oxide yellow and magnesium stearate.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

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 can be taken with or without food. Donepezil hydrochloride 23 mg tablets should be swallowed whole without the tablets being split, crushed or chewed. Donepezil hydrochloride orally disintegrating tablets should not be swallowed whole, but be allowed to dissolve on the tongue and followed with water. Advise patients and caregivers that donepezil hydrochloride 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. All trademarks are the property of their respective owners. Manufactured for: Macleods Pharma USA, Inc. Princeton, NJ 08540 Manufactured by: Macleods Pharmaceuticals Ltd. Baddi, Himachal Pradesh, India. Rev August 2023

SPL PATIENT PACKAGE INSERT

SPL PATIENT PACKAGE INSERT SECTION

Donepezil Hydrochloride Tablets (doe-NEP-e-zil HYE-droe-KLOR-ide) • Tablets: 5 mg and 10 mg • Tablets: 23 mg Donepezil Hydrochloride Orally Disintegrating Tablets (doe-NEP-e-zil HYE-droe-KLOR-ide) • Orally Disintegrating Tablets: 5 mg and 10 mg Read this Patient Information that comes with donepezil hydrochloride before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your 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, 10 mg, and 23 mg, and as Donepezil Hydrochloride Orally Disintegrating Tablets (ODT; 5 mg and 10 mg). Except where indicated, all the information about donepezil hydrochloride in this leaflet also applies to donepezil hydrochloride orally disintegrating tablets. 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? Do not take donepezil hydrochloride if you are allergic to any of the ingredients in donepezil hydrochloride or to medicines that contain piperidines. Ask your doctor if you are not sure. See the end of this leaflet for a list of ingredients in donepezil hydrochloride. What should I tell my doctor before taking donepezil hydrochloride? Tell the doctor about all of your present or past health problems and conditions. 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. Talk to your doctor about the best way to feed your baby if you take donepezil hydrochloride. Tell the doctor about all the medicines you take, 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 you take 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 your medicines are NSAIDs. Taking NSAIDs and donepezil hydrochloride together may make you 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 you take donepezil hydrochloride before you have: • surgery • medical procedures • dental surgery or procedures. Know the medicines that you take. Keep a list of all your medicines. Show it to your doctor or pharmacist before you start a new medicine. How should you take donepezil hydrochloride? • Take donepezil hydrochloride exactly as prescribed by the doctor. Do not stop donepezil hydrochloride or change the dose yourself. Talk with your doctor first. • Take donepezil hydrochloride one time each day. Donepezil hydrochloride can be taken with or without food. • Donepezil hydrochloride 23 mg tablets should be swallowed whole. Do not split, crush, or chew the tablets. • Donepezil hydrochloride orally disintegrating tablet melts on the tongue. You should drink some water after the tablet melts. • If you miss a dose of donepezil hydrochloride, just wait. Take only the next dose at the usual time. Do not take 2 doses at the same time. • If donepezil hydrochloride is missed for 7 days or more, talk with your doctor before starting again. • If you take too much donepezil hydrochloride at one time, call your doctor or poison control center, or go to the emergency room right away. What are the possible side effects of donepezil hydrochloride? Donepezil hydrochloride may cause the following serious side effects: • slow heartbeat and fainting. This happens more often in people with heart problems. Call your doctor right away if you feel faint or lightheaded while taking donepezil hydrochloride. • more stomach acid. This raises the chance of ulcers and bleeding, especially when taking donepezil hydrochloride tablets 23 mg. The risk is higher for people who have had ulcers, or take aspirin or other NSAIDs. • worsening of lung problems in people with asthma or other lung disease. • seizures. • difficulty passing urine. Call your doctor right away if you have: • fainting. • heartburn or stomach pain that is new or won’t go away. • nausea or vomiting, blood in the vomit, dark vomit that looks like coffee grounds. • bowel movements or stools that look like black tar. • new or worse asthma or breathing problems. • seizures. • difficulty passing urine. The most common side effects of donepezil hydrochloride are: • nausea • diarrhea • not sleeping well • vomiting • muscle cramps • feeling tired • not wanting to eat These side effects may get better after you take donepezil hydrochloride for a while. This is not a complete list of side effects with donepezil hydrochloride. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should donepezil hydrochloride tablets be stored? Store donepezil hydrochloride tablets at room temperature between 59°F to 86°F (15°C to 30°C). Keep donepezil hydrochloride tablets and all medicines out of the reach of children. General information about donepezil hydrochloride Medicines are sometimes prescribed for conditions that are not mentioned in this Patient Information Leaflet. Do not use donepezil hydrochloride for a condition for which it was not prescribed. Do not give donepezil hydrochloride to other people, even if they have the same symptoms or condition. It may harm them. This leaflet summarizes the most important information about donepezil hydrochloride. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about donepezil hydrochloride tablets that is written for health professionals. For more information call 1-888-943-3210 or 1-855-926-3384. What are the ingredients in donepezil hydrochloride tablets? Active ingredient: donepezil hydrochloride Inactive ingredients: Donepezil hydrochloride tablets 5 mg and 10 mg film-coated tablets: lactose monohydrate, pregelatinised starch, microcrystalline cellulose, colloidal silicon dioxide and magnesium stearate. The film coating contains talc, propylene glycol, hypromellose and titanium dioxide. Additionally, the 10 mg tablet contains yellow iron oxide (synthetic) as a coloring agent. Donepezil hydrochloride 23 mg film-coated tablets: hydroxypropyl cellulose, lactose monohydrate, magnesium stearate and hypromellose. The reddish color film coating includes ferric oxide red, hypromellose, polyethylene glycol, talc and titanium dioxide. Donepezil hydrochloride orally disintegrating tablets 5 mg and 10 mg: mannitol, crospovidone, sucralose, sodium chloride, ferric oxide yellow and magnesium stearate. All trademarks are the property of their respective owners. Manufactured for: Macleods Pharma USA, Inc. ...

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Donepezil Hydrochloride Tablets USP 10 mg