Donepezil hydrochloride is a centrally acting, reversible, non-competitive acetylcholinesterase inhibitor. It is a first-line pharmacological agent for the symptomatic treatment of mild to moderate dementia of the Alzheimer's type. It works by increasing the concentration of acetylcholine in the synaptic cleft, thereby enhancing cholinergic neurotransmission, which is deficient in Alzheimer's disease. It is available as a film-coated tablet for oral administration.
Adult: Initial dose: 5 mg once daily, preferably at bedtime. Maintenance dose: After 4-6 weeks, the dose may be increased to 10 mg once daily if clinically indicated and tolerated.
Note: Administer orally, with or without food. The tablet should be swallowed whole with a glass of water. Bedtime administration may minimize potential cholinergic side effects like nausea and diarrhea. Do not crush or chew.
Donepezil selectively and reversibly inhibits the enzyme acetylcholinesterase (AChE) in the central nervous system. This inhibition reduces the breakdown of the neurotransmitter acetylcholine (ACh) in the synaptic cleft, leading to an increased concentration and prolonged action of ACh at cholinergic synapses.
Pregnancy: Category C (US FDA). Animal studies have shown evidence of fetotoxicity at high doses. There are no adequate and well-controlled studies in pregnant women. Donepezil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Alzheimer's disease is rare in women of childbearing potential.
Driving: Donepezil may cause dizziness, fatigue, and syncope, especially at initiation or dose escalation. Patients should be cautioned about operating machinery or driving until they are certain the medication does not affect them adversely.
| Ketoconazole, Itraconazole, Erythromycin | Increased plasma concentration of donepezil due to CYP3A4 inhibition. Monitor for increased cholinergic side effects. | Moderate |
| Rifampicin, Carbamazepine, Phenytoin, Phenobarbital | Decreased plasma concentration of donepezil due to CYP3A4 induction. May reduce therapeutic efficacy. | Moderate |
| Paroxetine, Fluoxetine, Quinidine | Increased plasma concentration of donepezil due to CYP2D6 inhibition. Monitor for side effects. | Moderate |
| Beta-blockers (e.g., Atenolol, Propranolol), Digoxin, Diltiazem, Verapamil | Additive effect on lowering heart rate (bradycardia). Increased risk of syncope and falls. | Major |
| Succinylcholine, Bethanechol | Additive cholinergic effects, potentially leading to excessive parasympathetic stimulation. | Major |
| NSAIDs (e.g., Ibuprofen, Diclofenac) | Increased risk of gastrointestinal bleeding due to donepezil's potential to increase gastric acid secretion. | Moderate |
| Anticholinergic drugs (e.g., Oxybutynin, Amitriptyline, Trihexyphenidyl) | Pharmacological antagonism; may reduce the therapeutic efficacy of donepezil. | Moderate |