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NERVOUS SYSTEM › PSYCHOANALEPTICS › ANTI-DEMENTIA DRUGS › Anticholinesterases
donepezil and memantine
N06DA52
Forms & Strengths
- Capsule, extended-release: donepezil HCl 10 mg / memantine HCl 7 mg
- Capsule, extended-release: donepezil HCl 10 mg / memantine HCl 14 mg
- Capsule, extended-release: donepezil HCl 10 mg / memantine HCl 21 mg
- Capsule, extended-release: donepezil HCl 10 mg / memantine HCl 28 mg
Adult Dosing
- Patients must be stabilized on donepezil 10 mg daily before switching to combination therapy
- Initial dose: donepezil 10 mg / memantine 7 mg once daily at bedtime
- Maintenance dose: Titrate up in 7 mg memantine increments at minimum 1-week intervals
- Maximum recommended dose: donepezil 10 mg / memantine 28 mg once daily
Pediatric Dosing
- Safety and efficacy in pediatric patients have not been established
- Indicated strictly for neurodegenerative conditions of aging
Indications
- Treatment of moderate to severe dementia of the Alzheimer's type in patients already stabilized on donepezil 10 mg
Mechanism of Action
- Donepezil: Reversible and selective inhibitor of acetylcholinesterase, increasing acetylcholine concentrations in the central nervous system
- Memantine: Low- to moderate-affinity uncompetitive NMDA receptor antagonist, preventing neurotoxicity from sustained glutamate excitotoxicity
Contraindications
- Known hypersensitivity to donepezil, piperidine derivatives, memantine, or any formulation excipients
- Severe hepatic impairment
Adverse Reactions
- Headache
- Dizziness
- Diarrhea
- Nausea
- Vomiting
- Anorexia
- Somnolence
- Bradycardia
Drug Interactions
- Cholinesterase inhibitors: Synergistic toxicity with succinylcholine-type muscle relaxants during anesthesia
- CYP3A4 and CYP2D6 inducers (e.g., rifampin, carbamazepine): May increase clearance and decrease efficacy of donepezil
- CYP3A4 and CYP2D6 inhibitors (e.g., ketoconazole, quinidine): May increase exposure and toxicity risk of donepezil
- Alkalinizing agents (e.g., carbonic anhydrase inhibitors, sodium bicarbonate): Decrease urinary excretion of memantine, increasing serum concentrations and toxicity risk
Curated Content: Needs Vetting Before Put to Clinical Use