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Pronunciation
(me MAN teen)
Generic Available (U.S.)
No
Index Terms
U.S. Brand Names
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
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:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease; although adverse cardiac events were infrequent in clinical trials, an increased incidence of cardiac failure, angina, bradycardia, and hypertension (compared with placebo) was observed.
• Hepatic impairment: Use with caution in patients with severe hepatic impairment.
• Ophthalmic disease: Worsening of corneal condition has been observed in a clinical trial; periodic ophthalmic exams during use are recommended (Canadian labeling).
• Renal impairment: Use with caution in patients with moderate-to-severe renal impairment; dose adjustments may be required.
• 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%), hypotension (2%), cardiac failure, cerebrovascular accident, syncope, transient ischemic attack
Central nervous system: Dizziness (5% to 7%), confusion (6%), headache (6%), anxiety (4%), depression (3%), hallucinations (3%), pain (3%), somnolence (3%), fatigue (2%), aggressive reaction (1% to 2%), ataxia, vertigo
Dermatologic: Rash
Gastrointestinal: Constipation (3% to 5%), diarrhea (5%), weight gain (3%), vomiting (2% to 3%), abdominal pain (2%), weight loss
Genitourinary: Urinary incontinence (2%), micturition
Hematologic: Anemia
Hepatic: Alkaline phosphatase increased
Neuromuscular & skeletal: Back pain (3%), hypokinesia
Ocular: Cataract, conjunctivitis
Respiratory: Cough (4%), dyspnea (2%), pneumonia
Miscellaneous: Influenza (4%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Agitation, agranulocytosis, allergic reaction, alopecia, amnesia, angina, anorexia, apathy, aphasia, apnea, arthralgia, aspiration pneumonia, asthma, atrial fibrillation, AV block, blurred vision, bradycardia, bronchitis, cardiac arrest, cellulitis, cerebral hemorrhage, cerebral infarction, cholelithiasis, claudication, colitis, conjunctival hemorrhage, coordination abnormal, corneal opacity, dehydration, delirium, delusion, depersonalization, diabetes mellitus aggravated, diplopia, disorientation, diverticulitis, DVT, dyskinesia, dysphagia, dysuria, emotional lability, encephalopathy, esophageal ulceration, extrapyramidal disorder, fecal incontinence, fever, gait disturbance, gastroenteritis, gastrointestinal hemorrhage, glaucoma, hearing decreased, hematuria, hemiplegia, hemoptysis, hepatic failure, hepatitis, hyper/hypoglycemia, hyperkinesia, hyperlipidemia, hypertonia, hyponatremia, hypothermia, ileus, impotence, inappropriate antidiuretic hormone secretion, INR increased, insomnia, involuntary muscle contractions, lethargy, leukopenia, libido increased, loss of consciousness, macula lutea degeneration, melena, MI, myoclonus, myopia, nasopharyngitis, nausea, neuralgia, neuropathy, neurosis, NMS, orthostatic hypotension, pancreatitis, pancytopenia, paranoid reaction, paresthesia, parkinsonism, paroniria, peripheral edema, personality disorder, pruritus, psychosis, ptosis, pulmonary edema, pulmonary embolism, QT prolongation, renal failure, retinal detachment, retinal hemorrhage, seizure, sepsis, skin ulceration, Stevens-Johnson syndrome, stupor, suicidal ideation, suicide attempt, supraventricular tachycardia, tardive dyskinesia, thrombocytopenia, thrombophlebitis, thrombotic thrombocytopenic purpura, tinnitus, tremor, torsade de pointes, upper respiratory tract infection, urinary retention, urinary tract infection, urticaria, visual acuity decreased, weakness, xerophthalmia
Drug Interactions
Carbonic Anhydrase Inhibitors: May decrease the excretion of Memantine. Exceptions: Brinzolamide; Dorzolamide. 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. Memantine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Memantine. Risk C: Monitor therapy
Storage
Store at 25°C (77°C); excursions permitted to 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: Partially hepatic, primarily independent of the CYP enzyme system; 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: Immediate release: 3-7 hours; Extended release: 9-12 hours
Excretion: Urine (74%; ~48% of the total dose as unchanged drug; undergoes active tubular secretion moderated by pH-dependent tubular reabsorption; excretion reduced by alkaline urine pH)
Dosage
Oral: Adults:
Alzheimer's disease:
Immediate release: Initial: 5 mg/day; increase dose by 5 mg/day to a target dose of 20 mg/day; wait ≥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
Extended release: Initial: 7 mg once daily, increase dose by 7 mg/day to a target maximum dose of 28 mg/day; wait ≥1 week between dosage changes
Note: When switching from the immediate release product to the extended release product, begin the extended release product the day after the last dose of the immediate release product. Patients on immediate release 10 mg twice daily should be switched to extended release 28 mg once daily.
Mild-to-moderate vascular dementia (unlabeled use): Immediate release: Initial: 5 mg/day, titrated by 5 mg/day weekly to a target dose of 10 mg twice daily (Orgogozo, 2002)
Dosage adjustment in renal impairment:
Mild impairment: No adjustment required
Moderate impairment:
U.S. labeling: No adjustment required
Canadian labeling: (Clcr 30-49 mL/minute): Initial: 5 mg once daily; after at least 1 week of therapy and if tolerated, may titrate up to 5 mg twice daily; may further titrate dosage upward in weekly increments to 20 mg/day according to suggested titration schedule
Severe impairment:
U.S. labeling: Clcr 5-29 mL/minute: Immediate release: Initial: 5 mg once daily; after at least 1 week of therapy and if tolerated, may titrate up to 5 mg twice daily; Extended release: Target dose of 14 mg/day
Note: When switching from the immediate release product to the extended release product, begin the extended release product the day after the last dose of the immediate release product. Patients on immediate release 5 mg twice daily should be switched to extended release 14 mg once daily.
Canadian labeling: Clcr 15-29 mL/minute: Initial: 5 mg once daily; after at least 1 week of therapy and if tolerated, may titrate up to 5 mg twice daily
Dosage adjustment in hepatic impairment:
Mild-to-moderate impairment: No adjustment required
Severe impairment: Use caution
U.S. labeling: No specific dosing recommendations
Canadian labeling: Avoid use
Administration: Oral
Administer without regard to meals. Extended release capsules may be swallowed whole or entire contents of capsule may be sprinkled on applesauce and swallowed immediately. Do not chew, crush, or divide.
Monitoring Parameters
Periodic ophthalmic exam (Canadian labeling)
Dietary Considerations
May be taken without regard to meals.
Patient Education
Take with or without food. May cause hypertension or headache. Report increase or changes in CNS symptoms (confusion, hallucinations, fatigue, aggressive reaction), chest pain or palpitations, dizziness or fainting, difficulty breathing or tightness in chest, or rash.
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
Monitor for hypertension, CNS changes, rash, and constipation on a regular basis throughout therapy.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Combination package, oral, as hydrochloride [titration pack contains two separate tablet formulations]:
Namenda®: Tablet: 5 mg (28s) and Tablet: 10 mg (21s)
Solution, oral, as hydrochloride:
Namenda®: 2 mg/mL (360 mL) [ethanol free, sugar free; contains propylene glycol; peppermint flavor]
Tablet, oral, as hydrochloride:
Namenda®: 5 mg, 10 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Namenda)
5 mg (60): $218.99
10 mg (60): $223.00
Tablets (Namenda Titration Pak)
(49): $167.00
References
Hort J, O'Brien JT, Gainotti G, et al, “EFNS Guidelines for the Diagnosis and Management of Alzheimer's Disease,” Eur J Neurol, 2010 [epub ahead of print].
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. Second Edition,” Am J Psychiatry, 2007, 164(12 Suppl):5-56.
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 May 2011
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