Drug Guide
Donepezil Hydrochloride and Memantine Hydrochloride
Classification
Therapeutic: Alzheimer's Disease Agent
Pharmacological: Cholinesterase Inhibitor and NMDA Receptor Antagonist
FDA Approved Indications
- Treatment of moderate to severe Alzheimer's disease
Mechanism of Action
Donepezil is a reversible cholinesterase inhibitor that increases acetylcholine levels in the brain; memantine is an NMDA receptor antagonist that modulates glutamate activity to protect neurons from excitotoxicity.
Dosage and Administration
Adult: Typically, 10 mg once daily at bedtime. Dose may be increased to 23 mg once daily after at least 3 months, based on tolerability.
Pediatric: Not approved for pediatric use.
Geriatric: Dosing as above, with careful monitoring for side effects.
Renal Impairment: Adjustments not usually necessary but monitor closely in severe impairment.
Hepatic Impairment: No specific adjustment; use with caution.
Pharmacokinetics
Absorption: Well absorbed orally, with minimal food effect.
Distribution: Widely distributed in tissues; high affinity for brain tissue.
Metabolism: Donepezil undergoes hepatic metabolism; memantine undergoes minimal hepatic metabolism.
Excretion: Primarily excreted via kidneys; active drug and metabolites.
Half Life: Donepezil: approximately 70 hours; memantine: approximately 60-80 hours.
Contraindications
- Hypersensitivity to donepezil, memantine, or any component.
Precautions
- Use with caution in cardiac conduction abnormalities, gastrointestinal ulcers, urinary tract obstruction, seizure disorders, or asthma. Monitor for cholinergic side effects and neuropsychiatric symptoms.
Adverse Reactions - Common
- Nausea (Common)
- Diarrhea (Common)
- Insomnia (Common)
- Dizziness (Common)
Adverse Reactions - Serious
- Bradycardia or heart block (Rare)
- Seizures (Rare)
- Gastrointestinal bleeding (Rare)
- Neuropsychiatric symptoms, including agitation, depression, hallucinations (Less common)
Drug-Drug Interactions
- Other cholinergic agents, anticholinergics, drugs affecting CYP enzymes, particularly CYP2D6 and CYP3A4.
Drug-Food Interactions
- None well documented.
Drug-Herb Interactions
- Caution with herbs affecting bleeding or CNS.
Nursing Implications
Assessment: Monitor cognitive function, behavioral changes, gastrointestinal, and cardiac symptoms.
Diagnoses:
- Risk for falls due to dizziness or syncope.
- Impaired memory or cognition.
Implementation: Administer as prescribed, assess for side effects, monitor cardiac status, and neuropsychiatric symptoms.
Evaluation: Evaluate cognitive status periodically and assess for adverse effects.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Report side effects such as nausea, dizziness, or behavioral changes.
- Do not crush or chew extended-release formulations.
- Inform about the importance of adherence and regular follow-up.
Special Considerations
Black Box Warnings:
- None specifically for combination use.
Genetic Factors: CYP450 enzyme polymorphisms may affect metabolism.
Lab Test Interference: None significant.
Overdose Management
Signs/Symptoms: Nausea, vomiting, salivation, bradycardia, and syncope.
Treatment: Supportive care, atropine for bradycardia, activated charcoal if ingestion was recent, and symptomatic treatment.
Storage and Handling
Storage: Store at room temperature away from moisture, light, and heat.
Stability: Stable under recommended storage conditions.