Generic Name

Donepezil

Mechanism

Donepezil is a reversible, selective acetylcholinesterase (AChE) inhibitor.
• Increases synaptic acetylcholine by preventing its hydrolysis, thereby enhancing cholinergic neurotransmission in the central nervous system.
• At therapeutic concentrations it also weakly inhibits butyrylcholinesterase (BuChE), augmenting the cholinergic effect in advanced disease stages.
• The inhibition is competitive and reversible, minimizing long‑term neurotoxicity.

Pharmacokinetics

• Absorption: Oral bioavailability ≈70 %; peak plasma concentration (T_max) 2–3 h, enhanced when taken with food.
• Distribution: Vd ≈ 1.5 L/kg; highly protein‑bound (~95 %) and freely penetrates the blood‑brain barrier.
• Metabolism: Primarily hepatic via CYP2D6 and CYP3A4; minor pathways include N‑dealkylation.
• Elimination: ~50 % renal (≈30 % unchanged, 20 % as metabolites).
• Half‑life: ~70 h; steady state achieved after ~1 month.
• Drug‑drug interactions: Strong CYP3A4 inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin) may alter plasma levels; caution with anticholinergic agents.

Indications

• Mild‑to‑moderate Alzheimer’s disease (AD): Cognitive and functional benefit, delay of progression.
• Moderate‑to‑severe AD: Continued symptomatic benefit; dosage up‑titration to 10 mg nightly.

Contraindications

• Contraindications: Hypersensitivity to donepezil or any excipient.
• Warnings
• Cardiac: Bradycardia, conduction blocks, syncope; pre‑existing AV block or arrhythmia warrants ECG evaluation.
• Gastrointestinal: Severe nausea, vomiting, or significant weight loss.
• Neurologic: Seizure (rare); avoid in patients with uncontrolled seizures.
• Liver/Kidney: No dose adjustment required for mild‑moderate impairment, but data limited in end‑stage disease.

Dosing

• Form: 5‑mg or 10‑mg tablets; do not chew or crush.
• Timing: Take at night; may be taken with or without food.
• Special instructions: For patients on beta‑blockers or digoxin, monitor cardiac rhythm after dose change.

Adverse Effects

Common (≥10 %)
• Nausea, vomiting
• Diarrhea
• Anorexia/weight loss
• Insomnia, vivid dreams
• Muscle cramps, fatigue

Serious (<1 %)
• Bradycardia, syncope, chest pain
• Atrioventricular block, arrhythmias
• Severe GI bleeding (rare)
• Seizure (very infrequent)

Monitoring

• Baseline: ECG (heart rate & rhythm), liver function tests, kidney function, weight.
• Follow‑up:
• Heart rate/ECG after starting or uptitrating in patients with cardiac disease.
• Weight, appetite, and GI tolerance quarterly.
• Cognitive assessments (MMSE, ADAS‑Cog) every 6 months to gauge efficacy.

Clinical Pearls

• Start low, go slow: Initiate at 5 mg to reduce GI toxicity; increase only after 4–6 weeks if tolerated.
• Once‑daily convenience: Once‑daily dosing improves adherence, especially in the elderly.
• Avoid anticholinergics: Concomitant anticholinergic medications negate benefit and worsen side‑effects.
• Cardiac caution: Perform ECG in patients with AV block, sick sinus syndrome, or on antiarrhythmic drugs; discontinue if new conduction abnormalities arise.
• Renal/hepatic impairment: No dose adjustment needed for mild‑moderate impairment; cautious use in severe disease.
• Pediatric/Off‑label: Not approved for use in children or for dementia‑free elderly; data are limited.
• Drug‑drug interactions: Strong CYP3A4 inhibitors (e.g., ketoconazole) can increase exposure; consider monitoring or dose adjustment.
• Adherence aids: Use pill organizers and set bedtime reminders to ensure nightly dosing.

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• *This drug card provides a quick‑reference snapshot for medical students and practitioners, combining pharmacological depth with practical prescribing guidance.*