ARICEPT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ARICEPT (ARICEPT).
Reversible inhibitor of acetylcholinesterase, increasing acetylcholine levels in the synaptic cleft of the central nervous system.
| Metabolism | Hepatic via CYP3A4 and CYP2D6 isoenzymes; glucuronidation. |
| Excretion | Renal (57% unchanged drug, 17% as metabolites), fecal (30%), biliary (minimal) |
| Half-life | 70 hours (terminal elimination half-life; steady-state reached in 15-21 days; once-daily dosing appropriate) |
| Protein binding | 96% bound to plasma proteins (albumin and alpha1-acid glycoprotein) |
| Volume of Distribution | 12 L/kg (extensive tissue distribution, high CNS penetration) |
| Bioavailability | 100% oral (relative bioavailability; food does not affect rate or extent of absorption) |
| Onset of Action | Oral: 3-6 weeks for measurable cognitive improvement; single dose shows no acute effect |
| Duration of Action | 24 hours (with once-daily dosing; clinical effect persists for duration of therapy; reversible upon discontinuation) |
Initial: 5 mg orally once daily for 4-6 weeks; may increase to 10 mg once daily. Maximum: 10 mg per day. Route: oral. Frequency: once daily.
| Dosage form | TABLET |
| Renal impairment | GFR >=30 mL/min: No adjustment. GFR 15-29 mL/min: No specific adjustment, monitor for adverse effects. GFR <15 mL/min: Use with caution, no specific dosing guidelines available. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: No dose adjustment, but monitor. Child-Pugh C: Not studied; use caution. |
| Pediatric use | Not FDA approved for pediatric use. Limited data: doses up to 5 mg daily have been studied in some trials, but no established weight-based guidelines. |
| Geriatric use | Same as adult dosing. Monitor for cholinergic effects, including bradycardia and gastrointestinal upset. Renal function should be assessed, but no specific dose reduction is required solely for age. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ARICEPT (ARICEPT).
| Breastfeeding | It is not known whether donepezil is excreted in human breast milk. A study in rats showed that donepezil and/or metabolites are excreted in milk with concentrations up to 1.5 times plasma levels. M/P ratio unknown in humans. Caution is advised; consider developmental and health benefits of breastfeeding versus risk of infant exposure. |
| Teratogenic Risk | Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal studies, donepezil was not teratogenic at doses up to 10 times the maximum recommended human dose (MRHD) on a mg/m² basis, but resulted in increased fetal resorptions and decreased pup survival at doses 10 times MRHD. First trimester: risk cannot be ruled out; second and third trimesters: limited data, potential for cholinergic effects on fetus. |
■ FDA Black Box Warning
None
| Common Effects | Common cold Urinary incontinence Rash Nausea Diarrhea Insomnia difficulty in sleeping Weight loss Accidental injury |
| Serious Effects |
["Hypersensitivity to donepezil or piperidine derivatives"]
| Precautions | ["Anesthesia: may increase succinylcholine-type muscle relaxation","Cardiovascular conditions: bradycardia, heart block, syncope","Gastrointestinal: nausea, vomiting, diarrhea, weight loss, GI bleeding","Genitourinary: urinary obstruction","Neurologic: seizures","Pulmonary: asthma, COPD exacerbation"] |
| Food/Dietary | No specific food interactions. Take with or without food. High-fat meals may slow absorption but not affect clinical efficacy. |
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| Fetal Monitoring | Monitor maternal heart rate for bradycardia, especially if co-administered with other bradycardic agents. Assess for gastrointestinal adverse effects (nausea, vomiting, diarrhea) which may cause dehydration. In pregnancy, monitor fetal growth and well-being via ultrasound and non-stress testing as clinically indicated. No specific fetal monitoring required beyond standard prenatal care. |
| Fertility Effects | In animal studies, donepezil did not impair fertility in rats at doses up to 10 times the MRHD. No human data on fertility effects. Potential for cholinergic adverse effects (e.g., nausea, vomiting) to impact reproductive function, but no direct effect on fertility is established. |
| Clinical Pearls | Aricept (donepezil) is a reversible acetylcholinesterase inhibitor indicated for mild, moderate, and severe Alzheimer's disease. Titrate from 5 mg to 10 mg after 4-6 weeks; maximum dose 23 mg (severe only). Monitor for bradycardia, syncope, and gastrointestinal bleeding. Avoid concomitant NSAIDs. Administer at bedtime to minimize nausea and diarrhea. May cause vivid dreams or insomnia if taken in the morning. Significant drug interactions include anticholinergics, NSAIDs, and CYP3A4/2D6 inhibitors (e.g., ketoconazole, quinidine). |
| Patient Advice | Take once daily at bedtime to reduce stomach upset. · Do not crush or chew tablets; take with full glass of water. · May cause dizziness or fainting; rise slowly from sitting or lying. · Report slow heart rate, fainting, or black stools immediately. · Weight loss may occur; monitor weight regularly. · Avoid alcohol; may worsen dizziness and liver effects. |