donepezil hydrochloride
Pharmacologic class: Acetylcholinesterase inhibitor
Therapeutic class: Anti-Alzheimer's agent
Pregnancy risk category C
Action
Reversibly inhibits acetylcholinesterase hydrolysis in CNS, leading to increased acetylcholine level and temporary cognitive improvement in patients with Alzheimer's disease
Availability
Tablets: 5 mg, 10 mg, 23 mg
Tablets (orally disintegrating): 5 mg, 10 mg
Indications and dosages
➣ Mild to moderate Alzheimer's disease
Adults: Initially, 5 mg P.O. daily. After 4 to 6 weeks, may increase dosage to 10 mg at bedtime.
➣ Moderate to severe Alzheimer's disease
Adults: Initially, 10 mg P.O. daily. After 3 months, may increase dosage to 23 mg.
Contraindications
• Hypersensitivity to drug or piperidine derivatives
Precautions
Use cautiously in:
• cardiovascular disease, chronic obstructive pulmonary disease (COPD), asthma, or sick sinus syndrome
• patients at risk for developing ulcers, such as those with history of ulcer disease or those concurrently receiving NSAIDs
• pregnant or breastfeeding patients
• children (safety and efficacy not established).
Administration
• Give with or without food.
• For best response, give at bedtime.
Adverse reactions
CNS: headache, dizziness, vertigo, fatigue, depression, aggression, irritability, restlessness, nervousness, paresthesia, insomnia, abnormal dreams, tremor, aphasia, seizures
CV: chest pain, bradycardia, hypertension, hypotension, vasodilation, atrial fibrillation, heart block
EENT: cataracts, blurred vision, eye irritation, sore throat
GI: nausea, vomiting, diarrhea, anorexia, bloating, epigastric pain, fecal incontinence, GI bleeding
GU: urinary frequency, increased libido, bladder outflow obstruction
Metabolic: dehydration
Musculoskeletal: muscle cramps, arthritis, bone fracture
Respiratory: dyspnea, bronchitis
Skin: pruritus, urticaria, bruising, diaphoresis, rash, flushing
Other: toothache, decreased appetite, weight loss, hot flashes, influenza
Interactions
Drug-drug. Anticholinergics: reduced donepezil effects
Anticholinesterases, cholinomimetics: synergistic effects
Carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin: accelerated donepezil elimination
NSAIDs: increased risk of GI bleeding
Patient monitoring
☞ Watch closely for increased bronchoconstriction in patients with history of asthma or COPD.
• Assess cardiovascular status. Drug may cause bradycardia from increased vagal tone.
• Monitor closely for signs and symptoms of GI ulcers and bleeding, especially if patient takes NSAIDs concurrently.
Patient teaching
• Advise patient to take drug at bedtime with or without food.
• Instruct patient to allow orally disintegrating tablet to dissolve under tongue and then follow with a glass of water.
• Tell patient not to split, crush, or chew 23-mg tablet.
• Inform patient that drug may slow the heart rate, leading to fainting episodes.
☞ Instruct patient to immediately report signs or symptoms of GI ulcers ("coffee-ground" vomitus, black tarry stools, and abdominal pain), or irregular heartbeat.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.