donepezil, memantine and Ginkgo folium

N06DA53

Forms & Strengths

Combination product availability varies globally, primarily in specific markets as fixed-dose combination capsules or co-packaged blisters containing donepezil hydrochloride, memantine hydrochloride, and Ginkgo biloba leaf extract (Ginkgo folium)
Common individual component strengths frequently co-formulated: Donepezil 5 mg / Memantine 10 mg / Ginkgo folium 80 mg or 120 mg

Adult Dosing

Moderate to severe Alzheimer's disease: Titrated slowly to minimize adverse effects, typically initiating with the lowest available component doses (e.g., donepezil 5 mg, memantine 5-10 mg, and ginkgo 40-80 mg daily)
Maintenance dosing determined by individual component tolerability and clinical response, generally not exceeding donepezil 10 mg, memantine 20 mg, and standard therapeutic doses of Ginkgo folium daily

Pediatric Dosing

Not indicated for pediatric patients
Safety and efficacy have not been established in children or adolescents with neurodegenerative or cognitive disorders

Indications

Symptomatic treatment of moderate to severe Alzheimer's disease
Improvement of cognitive function, daily functioning, and global clinical assessment in dementia of the Alzheimer's type

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 excitotoxic glutamate-mediated neuronal cell death
Ginkgo folium: Contains flavonoid glycosides and terpene lactones that exhibit antioxidant properties, scavenge free radicals, improve microcirculation, and inhibit platelet-activating factor

Contraindications

Known hypersensitivity to donepezil, piperidine derivatives, memantine, Ginkgo biloba preparations, or any excipients in the formulation
Severe hepatic impairment (for donepezil/memantine components where applicable)
Active bleeding disorders, concurrent anticoagulant or antiplatelet therapy (due to the bleeding risk associated with Ginkgo folium)

Adverse Reactions

Nausea, diarrhea, vomiting, anorexia, and weight loss (primarily cholinergic effects from donepezil)
Dizziness, headache, confusion, somnolence, hallucinations, and fatigue (from memantine and donepezil)
Increased risk of bleeding, bruising, gastrointestinal upset, and allergic skin reactions (associated with Ginkgo folium)
Bradycardia, syncope, and prolongation of the QTc interval

Drug Interactions

Anticoagulants and antiplatelet agents (e.g., warfarin, aspirin): Increased risk of hemorrhage when combined with Ginkgo folium
CYP3A4 and CYP2D6 inhibitors/inducers (e.g., ketoconazole, erythromycin, carbamazepine): May alter the clearance and plasma concentrations of donepezil
Anticholinergic agents: May antagonize the therapeutic effects of acetylcholinesterase inhibitors like donepezil
Alkalizing agents (e.g., carbonic anhydrase inhibitors, sodium bicarbonate): May decrease urinary excretion of memantine, leading to elevated serum concentrations and toxicity

Curated Content: Needs Vetting Before Put to Clinical Use