Donepezil Hydrochloride

DONEPEZIL HYDROCHLORIDE- donepezil hydrochloride tablet, film coated
BIOMES PHARMACEUTICALS LLC

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.

2 DOSAGE AND ADMINISTRATION

2.1 Dosing in Mild to Moderate Alzheimer’s Disease

The recommended starting dosage of donepezil hydrochloride tablets, USP is 5 mg administered once per day in the evening, just prior to retiring. The maximum recommended dosage of donepezil hydrochloride tablets, USP 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 tablets, USP 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, USP should be taken in the evening, just prior to retiring. Donepezil hydrochloride tablets can be taken with or without food.

3 DOSAGE FORMS AND STRENGTHS

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, round, biconvex film coated debossed with “V” on one side and “14” on other side.
  • The 10 mg tablets are pale yellow, round, biconvex film coated debossed with “V” on one side and “15” on other side

4 CONTRAINDICATIONS

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

5 WARNINGS AND PRECAUTIONS

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 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.

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.

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)]

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 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/dayDonepezil Hydrochloride

(n = 350)

%

10 mg/dayDonepezil Hydrochloride

(n = 315)

%

Nausea

1

1

3

Diarrhea

0

< 1

3

Vomiting

< 1

< 1

2

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2021. All Rights Reserved.