Memantine
Non‑competitive NMDA receptor antagonist
Generic Name
Non‑competitive NMDA receptor antagonist
Mechanism
- Non‑competitive NMDA receptor antagonist that binds to the glycine‑cooperative site within the ion channel.
- Inhibits excessive glutamate‑mediated excitotoxicity without disrupting basal neurotransmission.
- Stabilizes neuronal electrophysiology, reduces oxidative stress, and preserves synaptic plasticity.
Pharmacokinetics
- Absorption: Oral bioavailability ~60 %; Cmax 24 h post‑dose.
- Distribution: Highly bound to plasma proteins (~73 %); crosses the blood‑brain barrier readily.
- Metabolism: Minimal hepatic metabolism via CYP3A4 and UGT1A9; small metabolite (N‑acetyl‑memantine).
- Elimination: Primarily renal (~83 % unchanged); half‑life ~60 h in healthy adults; prolonged to ~80 h in renal impairment.
- Drug interactions: No clinically significant CYP inhibition/induction; caution with nephrotoxic agents or extreme renal dysfunction.
Indications
- Alzheimer’s disease: Mild‑to‑moderate (5 mg BID) and severe (10 mg BID) forms.
- Vascular dementia (off‑label) when cognitive decline is evident.
- Other neurodegenerative disorders (Parkinson’s disease dementia, frontotemporal dementia) on a case‑by‑case basis.
Contraindications
- Absolute contraindication: Severe renal impairment (CrCl < 30 mL/min) unless dose adjusted.
- Moderate renally impaired: Dose reduction to 5 mg BID.
- Pregnancy/ lactation: Category C; use only if benefits outweigh risks.
- Sudden withdrawal: May precipitate psychosis or withdrawal seizures—taper over 1–2 weeks if discontinuation is needed.
Dosing
| Stage | Dose | Titration | Adjunct Steps |
| Initiation | 5 mg BID | Increase by 5 mg BID each week up to 10 mg BID (5 mg AM/PM). | Monitor for tolerability. |
| Maintenance | 10 mg BID | Stable after 4 – 6 weeks. | Evaluate cognitive status quarterly. |
| Renal impairment | CrCl ≥ 50 mL/min: 10 mg BID. < 30 mL/min: 5 mg BID, titrate cautiously. | Adjust per renal function. | Regular drug checks. |
• Administer with food to reduce GI symptoms.
• Missed dose: skip, resume first scheduled dose next day; do not double dose.
Adverse Effects
- Common (≥ ≥ 5 %)
- Nausea, dizziness, headache, confusion, fatigue.
- Psychosis, agitation (especially in severe dementia).
- Serious (≥ ≤ 5 %)
- Seizure exacerbation (rare).
- Severe orthostatic hypotension.
- Acute renal failure (in predisposed patients).
Monitoring
- Renal function: Creatinine, eGFR at baseline, every 2–3 months thereafter.
- Neurologic assessment: MMSE or MoCA for cognitive status; monitor for new neuropsychiatric symptoms.
- Electrolytes: Baseline; repeat if signs of arrhythmia.
- Concomitant medications: Review for nephrotoxic or CNS‑depressants.
Clinical Pearls
- Dosing Flexibility: The 5 mg BID titration schedule allows rapid count-down in patients prone to intolerable dizziness or confusion—particularly useful in hospitalized settings.
- Neuroprotective Complement: Combining memantine with cholinesterase inhibitors (donepezil, rivastigmine) offers additive effect on attention and processing speed in moderate dementia.
- Initiate with Low Dose: Even a single 5 mg daily dose can restore short‑term memory in patients with mild disease; this “micro‑dose” approach is often more acceptable to caregivers.
- Withdrawal Plan: If discontinuation becomes necessary, plan a gradual taper (e.g., 10 mg BID → 5 mg BID → 5 mg daily → none) over 2 weeks to prevent rebound psychosis.
- Renal–Nephrology Collaboration: For those with CKD, the 5 mg BID regimen can be maintained longer, provided CrCl remains > 40 mL/min; 0.3 mg/kg/day dosing is a practical alternative.
- Beware of Polypharmacy: While memantine’s profile is benign, co‑administration of other NMDA antagonists (e.g., ketamine, amantadine) can potentiate CNS depression.
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• *This drug card is intended for educational purposes; always corroborate with the latest prescribing information and clinical guidelines.*