Donepezil- Tedapharm
Donepezil
Category:
Dementia symptoms treatment adjunct.
(USP DI)
Mechanism of action
Donepezil is a specific noncompetitive reversible inhibitor of acetylcholinesterase (AChE), and appears to exert its therapeutic effect by enhancing cholinergic function. By inhibiting the hydrolysis of acetylcholine by AChE, donepezil increases acetylcholine concentrations, thus enhancing cholinergic function.
(USP DI)
Pharmacokinetics
Absorption Well absorbed
Protein binding 96%
Bioavailability 100% (relative)
Biotransformation It is metabolized by the CYP-450 isoenzyme 2D6 and 3A4, and undergoes gluuronidation
Half-Life Approximately 70 hours
Time to Peak Concentration 3-4 hours
Elimination Approximately 57% and 15% of the total dose is recovered in urine and feces respectively, 28% remains unrecovered
(Facts) (USP DI) (Martindale)
Indications:
- Alzheimer disease: For the treatment of dementia of the Alzheimer type. Efficacy has been demonstrated in patients with mild to moderate Alzheimer disease, as well as in patients with severe Alzheimer disease.
- Unlabaled uses: Possible treatment for vascular dementia, poststroke aphasia, and improvement of memory in multiple sclerosis patients.
)Facts( (PDR)
Contraindications:
Hypersnsitivity to donepezil or to piperidine derivatives.
(Facts)
Warnings & Precutions:
1- Anesthesia: donepezil as a cholinesterase inhibitor , is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.
2- Because of 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.
3- Cholinesterase inhibitor(donepezil) may be expected to increase gastric acid secretion due to increased cholinergic activity.
4- Cholinomimetics are believed to have some potential to cause generalized convulsions. However , seizure activity also may be a manifestation of Alzheimer s disease.
5- Donepezil should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
6- Although not observed in clinical trials, cholinomimetics may cause bladder outflow obstruction.
( PDR)
Pregnancy
FDA Pregnancy category C.
Adequate and well-controlled studies have not been done in humans. Donepezil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
( USP DI-PDR)
Breast-feeding
It is not known whether donepezil is distributed in to breast milk, however, use of donepezil is not recommended during breast-feeding.
( USP DI)
Drug Interactions:
1- Donepezil has the potential to interfere with the activity of anticholinergic medications.
2- A synergistic effect may be expected when donepezil is given concurrently with succinylcholine, similar neuromuscular-blocking agents, or cholinergic agonists, such as bethanechol.
3- Donepezil increase gastric acid secretions caused by increased cholinergic activity.
4- Hepatic metabolism of donepezil via the cytochrome P450 system has been demonstrated; plasma concentrations of donepezil may be raised by drugs that inhibit the isoenzyme CYP3A4 such as ketoconazole, itraconazole, and erythromycin, and by those that inhibit the isoenzyme CYP2D6 such as fluoxetine and quinidine.
5- Plasma-donepezil concentrations may be reduced by enzyme inducers such as rifampicin, phenytoin, carbamazepine, alcohol, Phenobarbital and dexamethasone.
(Martindale-Facts)
Adverse Reactions:
Anorexia, diarrhea, fatigue, insomnia, muscle cramps, nausea, vomiting, abnormal dreams, arthritis, constipation, dizziness, ecchymosis, frequent urination, headache, mental depression, pain, somnolence, syncope, weight loss, aphasia, ataxia, atrial fibrillation, bloating, blurred vision, bronchitis, cataract, chest or epigastric pain, dehydration, diaphoresis, dyspnea, eye irritation, fecal incontinence, gastrointestinal bleeding, hot flashes, hypertension or hypotension, increased libido, mood or mental changes, including abnormal crying, aggression, agitation, delusions, irritability, nervousness, or restlessness, nocturia, parasthesia, pharyngitis, pruritus, tremor, upper respiratory infection, urinary incontinence, urinary tract infection, urticaria, vasodilation, vertigo, sweating, angina, bradycardia, extrapyramidal symptoms, seizures, confusion, minor increases in serum creatine kinase
( USP DI)
Overdosage
Clinical effects of overdosage
Bradycardia , hypotension , increasing muscle weakness ( may result in death if respiratory muscles are involved) sever nausea, vomiting, salivation and sweating, seizures respiratory depression.
Treatment of overdose- Tertiary anticholinergics such as atropine may be used as antidotes.
( USP DI)
Dosage & Administration
- Mild to moderate Alzheimer disease: 5 or 10 mg once daily.
- Severe Alzheimer disease: 10 mg administered once daily.
( USP DI)
Storage:
Store below 30oC and protect from heat & direct light.
(USP DI)
How supplied:
Donepezil–Tedapharm is as available as 10 mg, oval, yellow, scored & coated tablets. There are blisters of 10's in abox of 30's.