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Medication Safety Issues
Sound-alike/look-alike issues:
Memantine may be confused with mesalamine
Pronunciation
(me MAN teen)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of moderate-to-severe dementia of the Alzheimer's type
Use: Unlabeled/Investigational
Treatment of mild-to-moderate vascular dementia; mild cognitive impairment
Pregnancy Risk Factor
B
Pregnancy Considerations
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
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with severe hepatic impairment.
• Renal impairment: Use with caution in patients with severe renal impairment; dose adjustment recommended.
• Seizure disorder: Use with caution in patients with a history of seizure disorder; may increase risk of seizures.
Other warnings/precautions:
• Urine pH: 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
Postmarketing and/or case reports (limited to important or life-threatening): AV block, cerebral infarction, dyskinesia, dysphagia, hepatic failure, hyperlipidemia, hypoglycemia, ileus, NMS, pancreatitis, renal failure, QT prolongation, seizure, Stevens-Johnson syndrome, sudden death, tardive dyskinesia, thrombocytopenia
Drug Interactions
Carbonic Anhydrase Inhibitors: May decrease the excretion of Memantine. Risk C: Monitor therapy
Sodium Bicarbonate: May decrease the excretion of Memantine. Risk C: Monitor therapy
Trimethoprim: May enhance the adverse/toxic effect of Memantine. Specifically, the risk of myoclonus and/or delirium may be increased. Trimethoprim may increase the serum concentration of Memantine. Memantine may increase the serum concentration of Trimethoprim. Risk C: Monitor therapy
Storage
Store at controlled room temperature of 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Glutamate, the primary excitatory amino acid in the CNS, may contribute to the pathogenesis of Alzheimer's disease (AD) by overstimulating various glutamate receptors leading to excitotoxicity and neuronal cell death. Memantine is an uncompetitive antagonist of the N-methyl-D-aspartate (NMDA) type of glutamate receptors, located ubiquitously throughout the brain. Under normal physiologic conditions, the (unstimulated) NMDA receptor ion channel is blocked by magnesium ions, which are displaced after agonist-induced depolarization. Pathologic or excessive receptor activation, as postulated to occur during AD, prevents magnesium from reentering and blocking the channel pore resulting in a chronically open state and excessive calcium influx. Memantine binds to the intra-pore magnesium site, but with longer dwell time, and thus functions as an effective receptor blocker only under conditions of excessive stimulation; memantine does not affect normal neurotransmission.
Pharmacodynamics/Kinetics
Distribution: 9-11 L/kg
Protein binding: 45%
Metabolism: Forms 3 metabolites (minimal activity)
Half-life elimination: Terminal: 60-80 hours; severe renal impairment (Clcr 5-29 mL/minute): 117-156 hours
Time to peak, serum: 3-7 hours
Excretion: Urine (57% to 82% unchanged); excretion reduced by alkaline 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
Mild-to-moderate vascular dementia (unlabeled use): 10 mg twice daily
Dosage adjustment in renal impairment:
Mild-to-moderate impairment: No adjustment required
Severe impairment: Clcr 5-29 mL/minute): 5 mg twice daily
Dietary Considerations
May be taken without regard to meals.
Patient Education
Take as directed with or without food. May cause hypertension (monitor if recommended); headache (consult prescriber for analgesic). Report increase or changes in CNS symptoms (confusion, hallucinations, fatigue, aggressive reaction); chest pain or palpitations, dizziness or fainting; difficulty breathing of tightness in chest; rash; alteration in elimination patterns, or other persistent adverse reactions. Breast-feeding precaution: Consult prescriber if breast-feeding.
Geriatric Considerations
In clinical trials, patients on memantine had less of a decline in cognitive function and activities of daily living (ADL) as compared to placebo. This was true for monotherapy with memantine, as well as combination therapy with donepezil, an acetylcholinesterase inhibitor.
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
Nursing: Physical Assessment/Monitoring
Assess therapeutic effectiveness and adverse reactions on a regular basis throughout therapy (eg, hypertension, CNS changes, rash, constipation). Teach patient possible side effects/appropriate interventions and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral: 2 mg/mL (360 mL) [alcohol free, dye free, sugar free; peppermint flavor]
Tablet, as hydrochloride: 5 mg, 10 mg
Combination package [titration pack contains two separate tablet formulations]: Memantine hydrochloride 5 mg (28s) and memantine hydrochloride 10 mg (21s)
Pricing: U.S. (www.drugstore.com)
Tablets (Namenda)
5 mg (60): $181.46
10 mg (60): $180.19
Tablets (Namenda Titration Pak)
(49): $148.61
References
Lipton, SA, “Failures and Successes of NMDA Receptor Antagonists: Molecular Basis for the Use of Open-Channel Blockers like Memantine in the Treatment of Acute and Chronic Neurologic Insults,” NeuroRx, 2004, 1:101-10.
Orgogozo JM, Rigaud AS, Stoffler A et al, “Efficacy and Safety of Memantine in Patients with Mild to Moderate Vascular Dementia: A Randomized, Placebo-Controlled Trial (MMM 300),” Stroke, 2002, 33:1834-39.
Rabins PV, Blacker D, Rovner BW, et al, “Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias,” October, 2007. Available at http://www.psych.org/psych_pract/treatg/pg/prac_guide.cfm
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.
Wilcock G, Mobius HJ, Stoffler A et al, “A Double-Blind, Placebo-Controlled Multicentre Study of Memantine in Mild to Moderate Vascular Dementia (MMM 500),” Int Clin Psychopharmacol, 2002, 17(6):297-305.
International Brand Names
Lexi-Comp.com
Last full review/revision December 2009
Content last modified December 2009
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