Section 05 · Monograph
Memantine
Reviewed Nov 2026FDA label
Namenda XRNMDA antagonist
- Forms
- IR: 5, 10mg | XR: 7, 14, 21, 28mg
- Dose
- Titrate weekly by 5mg to 28mg once daily (XR)
- MOA
- Noncompetitive NMDA receptor blockade
Indications
- Treatment of moderate to severe dementia of the Alzheimer's typeFDA-labeled
Off-Label Uses
- Mild Alzheimer's disease (used off-label; formal approval covers moderate-severe only)Off-label
- Vascular dementia / mixed dementiaOff-label
Mechanism of Action
- Low-to-moderate affinity, uncompetitive (open-channel blocking) antagonist at the NMDA-type glutamate receptor
- Blocks pathologic tonic activation of NMDA receptors caused by chronically elevated extracellular glutamate, reducing excitotoxic neuronal injury
- Rapid channel blocking/unblocking kinetics allow relative preservation of physiologic glutamatergic transmission needed for learning and memory
- Mechanistically independent of and complementary to cholinesterase inhibition
Full Dosing
Adult / usual
- Namenda XR (extended-release capsule): initiate 7 mg once daily
- Increase in 7 mg increments at intervals of at least 1 week, to a target maintenance dose of 28 mg once daily, as tolerated
- Capsule may be swallowed whole or opened and sprinkled on applesauce; beads should not be divided, chewed, or crushed
- Immediate-release tablets/solution (Namenda): initiate 5 mg once daily, titrate by 5 mg/week increments to a maintenance regimen of 10 mg twice daily
Renal
- Severe renal impairment (CrCl 5-29 mL/min): target maintenance dose reduced to 14 mg once daily
Hepatic
- No dosage adjustment required for mild-to-moderate hepatic impairment
Contraindications
- Known hypersensitivity to memantine hydrochloride or any formulation excipients
Drug Interactions
- Drugs that alkalinize urine (carbonic anhydrase inhibitors, sodium bicarbonate) can reduce renal clearance of memantine by up to ~80%, increasing accumulation risk
- Other NMDA receptor antagonists (amantadine, ketamine, dextromethorphan): use with caution due to potential additive CNS effects
- Drugs eliminated via the same renal cationic transport system (cimetidine, ranitidine, quinidine, triamterene, hydrochlorothiazide, metformin) may alter plasma levels of either agent
Adverse Effects
- Dizziness (most common)
- Headache
- Confusion
- Constipation
- Somnolence
- Hypertension
- Vomiting
- Back pain and increased weight
Monitoring Parameters
- Renal function (creatinine clearance) at baseline and periodically
- Conditions that raise urine pH (UTIs, renal tubular acidosis, dietary changes) that could impair drug clearance
- Cognitive and behavioral status over time using standardized assessments
- Signs of dizziness, confusion, or sedation, especially during dose titration (fall risk)
- Blood pressure periodically
Pregnancy & Lactation
- Limited human pregnancy data; older labeling classified memantine as Pregnancy Category B
- Animal reproduction studies at high multiples of maximum recommended human dose did not show clear teratogenicity
- Use during pregnancy only if potential benefit justifies potential risk
- Unknown whether excreted in human milk; caution advised if used in a nursing mother