MEMANTINE HYDROCHLORIDE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Uncompetitive NMDA receptor antagonist with moderate affinity; blocks pathological tonic activation of glutamatergic neurotransmission while preserving physiologic phasic activation.

What the body does with it

Metabolism	Partially metabolized by CYP450 enzymes (CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1); primarily excreted unchanged in urine with minimal hepatic metabolism.
Excretion	Renal excretion of unchanged drug accounts for approximately 57-82% of the administered dose. Fecal excretion represents about 5-10% via biliary elimination. Overall, 80-90% is eliminated as parent compound or metabolites in urine.
Half-life	Terminal elimination half-life is 60-80 hours (mean ~70 hours) in young adults, extending to 100-120 hours in elderly patients. This long half-life allows once-daily dosing.
Protein binding	Approximately 45% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution is 10-12 L/kg, indicating extensive extravascular distribution beyond total body water, consistent with extensive tissue binding.
Bioavailability	Absolute bioavailability after oral administration is approximately 100% (well-absorbed, minimal first-pass metabolism).
Onset of Action	Clinical improvement in Alzheimer's disease symptoms may be observed after 2-4 weeks of daily oral dosing, with maximal benefits seen over 3-6 months.
Duration of Action	Symptomatic effects persist for the duration of treatment; withdrawal leads to gradual loss of benefit over weeks. Single-dose effects last approximately 24 hours.

Classification & Brands

Dosing & administration

Initial 5 mg orally once daily; may increase by 5 mg per week to target dose of 10 mg twice daily (20 mg/day).

Dosage form	TABLET
Renal impairment	CrCl 30-49 mL/min: 5 mg twice daily. CrCl 5-29 mL/min: 5 mg once daily. CrCl <5 mL/min: not recommended.
Liver impairment	Child-Pugh Class A and B: no adjustment needed. Child-Pugh Class C: not recommended.
Pediatric use	Not approved for pediatric use; safety and efficacy not established.
Geriatric use	No specific dose adjustments, but monitor renal function; elderly often have reduced CrCl; consider renal dosing.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Drugs that make urine alkaline (eg carbonic anhydrase inhibitors) may decrease excretion Generally well-tolerated with dizziness being the most common side effect.

Breastfeeding

It is unknown if memantine is excreted into human breast milk. M/P ratio not established. Due to potential adverse effects on infant nervous system development, breastfeeding is not recommended during memantine therapy.

Teratogenic Risk

Memantine hydrochloride is classified as Pregnancy Category B. Animal studies have not demonstrated teratogenic effects, but there are no adequate and well-controlled studies in pregnant women. First trimester: No evidence of structural anomalies in animal studies; human data insufficient. Second and third trimesters: Potential risk of fetal NMDA receptor antagonism affecting neuronal development; avoid use unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	Dizziness
Serious Effects

Absolute Contraindications

Hypersensitivity to memantine or any component of the formulation.

Clinical Precautions

Precautions

Increased risk of seizures; caution in patients with renal impairment (dose adjustment required); genitourinary conditions (e.g., urinary retention); possible elevation of intracranial pressure.

Clinical Tips & Counseling

Drug interactions

Loading safety data…