Dopezil

Donepezil hydrochloride.

Each tablet contains Donepezil hydrochloride 5 mg or 10 mg.

Pharmacology: Pharmacodynamics: Donepezil, a reversible inhibitor of the enzyme acetylcholinesterase, is postulated to exert its therapeutic effect by enhancing cholinergic function.
Pharmacokinetics: Donepezil is well absorbed. The rate and extent of absorption are not influenced by food intake. Maximum plasma levels are reached approximately 3-4 hours after oral administration. Following multiple-dose administration, steady state concentration (~14.2 ng/mL) is reached approximately within 15 days. Donepezil is approximately 96% bound to human plasma protein, 75% bound with albumin and approximately 21% bound with alpha₁-acid glycoprotein. Steady state volume of distribution (Vol_D) is 12 L/kg of body weight. Donepezil undergoes first pass metabolism by cytochrome P450 isoenzyme CYP2D6 and CYP3A4 and undergoes glucoronidation to four major metabolites, two of which are known to be active. Donepezil is both excreted in the urine and feces, elimination half life is about 70 hours.

For the treatment of dementia of Alzheimer type.

Recommended dose: Usual dosage: Mild to moderate alzheimer disease: 5 or 10 mg once daily.
Moderate to Severe Alzheimer disease: 10 or 23 mg once daily.*
(*Macrophar's Dopezil products available only 5 or 10 mg)
Initial dosage: 5 mg once daily
Dosage titration: Because the steady state is achieved approximately 15 days after it is started and the incidence of untoward effects may be influenced by the rate of dose escalation, a dose of 10 mg should not be achieved until patients have been on a daily dose of 5 mg for 4 to 6 weeks.
Mode of Administration: Donepezil hydrochloride is administered orally as conventional. The drug is administered once daily, usually in the evening at bedtime. Donepezil may be taken with or without food because food does not affect the rate or extent of absorption.

Sign and Symptoms: 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.
Treatment of overdose: Tertiary antcholinergics such as atropine may be used as an antidote for donepezil overdosage. Intravenous (IV) atropine 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 coadministered with quaternary antichlinergics such as glycopyrrolate. It is not known whether donepezil and/or its metabolites can be removed by dialysis (e.g. hemodialysis, peritoneal dialysis, hemofiltration).

Hypersensitivity to donepezil or to piperidine derivatives.

Cardiovascular effects: This effect may manifest as bradycardia or heart block in patients with and without known underlying cardiac conduction abnormalities.
GI effects: Peptic ulcer/GI bleeding: Through their primary action, cholinesterase inhibitors may be expected to increase gastric acid secretion because of increased cholinergic activity. Therefore, monitor patients closely for symptoms of active or occult GI bleeding, especially those at increased risk for developing ulcers (eg. those with a history of ulcer disease or those receiving concurrent non-steroidal anti-inflammatory drugs [NSAIDs]).
Nausea/Vomiting: Donepezil, as a predictable consequence of its pharmacological properties, produces diarrhea, nausea, and vomiting. These effects, when they occur, appear more frequently with the 10 mg/day dosage than with the 5 mg/day dosage and more frequently with the 23 mg dose than with the 10 mg dose. Although in most cases, these effects have been mild and transient, sometimes lasting 1 to 3 weeks, and have resolved during continued use of donepezil.
Genitourinary effects: Although not observed in clinical trials, cholinomimetics may cause bladder outflow obstruction.
Pulmonary effects: Because of their cholinomimetic actions, prescribe cholinesterase inhibitors with care to patients with a history of asthma or obstructive pulmonary disease.
Use in Children: There are no adequate and well-controlled trials to document the safety and efficacy of donepezil in any illness occuring in children.
This medicine is prescribed by a neurologist or a psychiatrist.

Use in Pregnancy: Category C.
There are no adequate or well-controlled studies in pregnant women. Use donepezil during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
Use in Lactation: It is not known whether donepezil is distributed into breast milk. Donepezil has no indication for use in nursing mothers.

Adverse effects are generally mild to moderate; the frequency of common adverse effects may be affected by the rate of dosage titration. The incidence of nausea, diarrhea, vomiting, insomnia, fatigue, and anorexia increases with increasing dose and with increasing age. Also, adverse effects occur more commonly in patients who are ≥85 years of age, female, or of low body weight.

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See Table 2.
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Keep in tight containers and store below 30°C.

Neurodegenerative Disease Drugs

N06DA02 - donepezil ; Belongs to the class of anticholinesterases. Used in the management of dementia.

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