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Pronunciation:

(me MAN teen)

U.S. Brand Names:

Namenda™

Synonyms:

Memantine Hydrochloride

Generic Available:

Use:

Treatment of moderate-to-severe dementia of the Alzheimer's type

Pregnancy Risk Factor:

Pregnancy Implications:

Teratogenic effects were not observed in animal studies. There are no studies in pregnant women.

Lactation:

Excretion in breast milk unknown/use caution

Contraindications:

Hypersensitivity to memantine or any component of the formulation

Warnings/Precautions:

Use caution with seizure disorders, hepatic impairment, or mild-to-moderate renal impairment. Use with severe renal impairment is not recommended. Clearance is significantly reduced by alkaline urine; use caution with medications, dietary changes, or patient conditions which may alter urine pH.

Adverse Reactions:

1% to 10%:

Cardiovascular: Hypertension (4%), cardiac failure, syncope, cerebrovascular accident, transient ischemic attack

Central nervous system: Dizziness (7%), confusion (6%), headache (6%), hallucinations (3%), pain (3%), somnolence (3%), fatigue (2%), aggressive reaction, ataxia, vertigo

Dermatologic: Rash

Gastrointestinal: Constipation (5%), vomiting (3%), weight loss

Genitourinary: Micturition

Hematologic: Anemia

Hepatic: Alkaline phosphatase increased

Neuromuscular & skeletal: Back pain (3%), hypokinesia

Ocular: Cataract, conjunctivitis

Respiratory: Cough (4%), dyspnea (2%), pneumonia

<1%: Allergic reaction, alopecia, amnesia, angina, apathy, aphasia, apnea, appetite increased, asthma, atrial fibrillation, blepharitis, blurred vision, bradycardia, cardiac arrest, cellulitis, cerebral hemorrhage, conjunctival hemorrhage, convulsions, coordination abnormal, corneal opacity, crying abnormal, dehydration, delirium, delusion, depersonalization, dermatitis, diabetes mellitus aggravated, diplopia, diverticulitis, dysuria, eczema, emotional lability, erythematous rash, esophageal ulceration, extrapyramidal disorder, eye pain, gastroenteritis, gastrointestinal hemorrhage, glaucoma, hearing decreased, hematuria, hemiplegia, hemoptysis, hyperkinesias, hypertonia, hypoesthesia, hyponatremia, hypotension, hypothermia, involuntary muscle contractions, lacrimation abnormal, leukopenia, libido increased, macula lutea degeneration, melena, MI, myopia, nervousness, neuralgia, neuropathy, neurosis, paranoid reaction, paresthesia, paroniria, personality disorder, postural hypotension, pruritus, psychosis, ptosis, pulmonary edema, pulmonary embolism, retinal detachment, retinal hemorrhage, skin ulceration, sleep disorder, stupor, suicide attempt, thinking abnormal, thrombophlebitis, tinnitus, tremor, urinary retention, urticaria, visual acuity decreased, xerophthalmia

Overdosage/Toxicology:

Loss of consciousness, psychosis, restlessness, somnolence, stupor, and visual hallucinations were reported following ingestion of memantine 400 mg. In case of overdose, treatment should be symptomatic and supportive. Elimination may be increased by acidifying the urine.

Drug Interactions:

Carbonic anhydrase inhibitors: Carbonic anhydrase inhibitors may alkalinize the urine; clearance of memantine is decreased 80% at urinary pH 8.

Sodium bicarbonate: Sodium bicarbonate may alkalinize the urine; clearance of memantine is decreased 80% at urinary pH 8.

Stability:

Store at controlled room temperature of 15°C to 30°C (59°F to 86°F).

Mechanism of Action:

Memantine reduces the decline in function in Alzheimer's disease by binding to N-methyl-D-aspartate (NMDA) receptors and blocking the actions of glutamate. Glutamate is an amino acid which may contribute to the pathogenesis of Alzheimer's disease by over-stimulating the NMDA receptor. Memantine does not prevent or slow neurodegeneration associated with Alzheimer's disease.

Pharmacodynamics/Kinetics:

Distribution: 9-11 L/kg

Protein binding: 45%

Metabolism: Forms three metabolites (minimal activity)

Half-life elimination: Terminal: 60-80 hours

Time to peak, serum: 3-7 hours

Excretion: Urine (57% to 82% unchanged); excretion affected by urine pH

Dosage:

Oral: Adults: Alzheimer's disease: Initial: 5 mg/day; increase dose by 5 mg/day to a target dose of 20 mg/day; wait at least 1 week between dosage changes. Doses >5 mg/day should be given in 2 divided doses.

Suggested titration: 5 mg/day for 1 week; 5 mg twice daily for 1 week; 15 mg/day given in 5 mg and 10 mg separated doses for 1 week; then 10 mg twice daily

Dosage adjustment in renal impairment:

Moderate impairment: Consider dose reduction; specific recommendations are not available

Severe impairment: Use is not recommended

Dietary Considerations:

May be taken with or without food.

Patient Education:

Inform prescriber of any prescription, OTC medication, or herbal products you are using and any allergies you have. Do not take any new medications during therapy without consulting prescriber. Take as directed with or without food. May cause hypertension (monitor if recommended); headache (consult prescriber for analgesic); CNS changes (confusion, hallucinations, fatigue, aggressive reaction); consult prescriber if persistent. Report chest pain or palpitations, dizziness or fainting; difficulty breathing of tightness in chest; rash; alteration in elimination patterns, increase in any adverse CNS symptoms, or other persistent adverse reactions. Breast-feeding precaution: Consult prescriber if breast-feeding.

Dental Health: Effects on Dental Treatment:

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

No information available to require special precautions

Dosage Forms:

Tablet, as hydrochloride (Namenda™): 5 mg, 10 mg

Combination package (Namenda™) [titration pack contains 2 separate tablet formulations]: Memantine hydrochloride 5 mg (28s) and memantine hydrochloride 10 mg (21s)

International Brand Names:

Akatinol® (AR, CO, LU); Akatinol Memantine® (DO, GT, HN, PA, RU, SV); Axura® (AT, CH, DE, PL); Conexine® (AR); Ebixa® (AT, BE, CH, DE, DK, ES, FI, FR, GB, IE, NO, PL, SE, SI); Neuroplus® (AR)

References

Reisberg B, Doody R, Stoffler A, et al, "Memantine in Moderate-to-Severe Alzheimer's Disease,"N Engl J Med, 2003, 348(14):1333-41.

Tariot PN, Farlow MR, Grossberg GT, et al, "Memantine Treatment in Patients With Moderate to Severe Alzheimer Disease Already Receiving Donepezil: A Randomized Controlled Trial. The Memantine Study Group,"JAMA, 2004, 291(3):317-24.

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