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- Memantine HCl
- Memantine Hydrochloride
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Extended Release 24 Hour, Oral, as hydrochloride:
Namenda XR: 7 mg, 14 mg, 21 mg, 28 mg
Namenda XR Titration Pack: 7 mg (7s) and 14 mg (7s) and 21 mg (7s) and 28 mg (7s)
Solution, Oral, as hydrochloride:
Namenda: 10 mg/5 mL (360 mL) [peppermint flavor]
Generic: 2 mg/mL (360 mL)
Tablet, Oral, as hydrochloride:
Namenda: 5 mg [contains fd&c blue #2 (indigotine), fd&c yellow #6 (sunset yellow)]
Namenda: 10 mg
Namenda Titration Pak: 5 mg (28s) and 10 mg (21s) [contains fd&c blue #2 (indigotine), fd&c yellow #6 (sunset yellow)]
Generic: 5 mg, 10 mg, 5 mg (28s) and 10 mg (21s)
Brand Names: U.S.
- Namenda Titration Pak
- Namenda XR
- Namenda XR Titration Pack
- N-Methyl-D-Aspartate Receptor Antagonist
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.
9 to 11 L/kg
Partially hepatic, primarily independent of the CYP enzyme system; forms 3 metabolites (minimal activity)
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)
Time to Peak
Time to peak, serum: Immediate release: 3 to 7 hours; Extended release: 9 to 12 hours
Terminal: ~60 to 80 hours
Special Populations: Renal Function Impairment
Mean AUC0-∞ increased by 4%, 60%, and 115% in patients with mild, moderate, and severe renal impairment, respectively. The terminal elimination half-life increased by 18%, 41%, and 95% in patients with mild, moderate, and severe renal impairment, respectively.
Special Populations: Hepatic Function Impairment
Terminal elimination half-life increased by ~16% in patients with moderate hepatic impairment.
Special Populations: Gender
Women had ~45% greater exposure than men; however, there was no difference in exposure when body weight was taken into account.
Use: Labeled Indications
Alzheimer disease: Treatment of moderate to severe dementia of the Alzheimer type.
Off Label Uses
Vascular dementia (mild to moderate)
Data from two meta-analysis evaluating two randomized, double-blind, parallel-group, placebo controlled trials suggest that memantine may be beneficial for the treatment of mild to moderate vascular dementia based on a small, statistically significant effect on cognitive function. However, no significant difference was identified for clinical global ratings of change, suggesting cognitive improvements may not be clinically detectable. Additional data is necessary to further define the role of memantine in this condition.
Based on the American Psychiatric Association practice guidelines for the treatment of patients with Alzheimer Disease and other dementias, memantine given for vascular dementia is not supported by the evidence and further trials are needed.
Hypersensitivity to memantine or any component of the formulation
Alzheimer disease, moderate to severe: Oral:
Immediate release: Initial: 5 mg daily; increase dose by 5 mg daily to a target dose of 20 mg daily; wait ≥1 week between dosage changes. Doses >5 mg daily should be given in 2 divided doses. Note: If treatment is interrupted for longer than several days, the treatment may need to be restarted at a lower dose and retitrated.
Suggested titration: 5 mg daily for ≥1 week; 5 mg twice daily for ≥1 week; 15 mg daily given in 5 mg and 10 mg separate doses for ≥1 week; then 10 mg twice daily
Extended release: Initial: 7 mg once daily, increase dose by 7 mg daily to a target maximum dose of 28 mg once daily; wait ≥1 week between dosage changes (if previous dose well tolerated)
Note: When switching from 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.
Missed dose: If a single dose is missed, do not double up on the next dose; take the next dose as scheduled. If several days of dosing are missed, dosing may need to be resumed at lower doses and retitrated.
Vascular dementia, mild to moderate (off-label use): Oral: Immediate release: Initial: 5 mg once daily; titrate in increments of 5 mg daily each week to a target dose of 10 mg twice daily (Orgogozo, 2002; Wilcock 2002). Additional data may be necessary to further define the role of memantine in this condition.
Refer to adult dosing.
Dosing: Renal Impairment
Note: Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.
Mild impairment: No dosage adjustment necessary.
U.S. labeling: No dosage adjustment necessary.
Canadian labeling: (CrCl 30-49 mL/minute): Initial: 5 mg once daily; after at least 1 week of therapy and if tolerated, titrate up to 5 mg twice daily; based on clinical response and tolerability, may further titrate dosage upward in weekly increments to 20 mg daily according to suggested titration schedule.
U.S. labeling: CrCl 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 a target dose of 5 mg twice daily; Extended release: Target dose of 14 mg once daily.
Note: When switching from 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: CrCl 15-29 mL/minute: Initial: 5 mg once daily; after at least 1 week of therapy and if tolerated, may titrate up to a target dose of 5 mg twice daily
Dosing: Hepatic Impairment
Mild-to-moderate impairment: No dosage adjustment necessary.
U.S. labeling: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.
Canadian labeling: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use is not recommended.
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. Withdraw and administer oral solution with provided dosing device; dose should be slowly squirted into the corner of the patient’s mouth. Do not mix oral solution with any other liquid. The Canadian labeling recommends tablets to be swallowed whole with water.
Capsule (extended release): Store between 20°C to 25°C (68°F to 77°F).
Tablet, oral solution: Store at 25°C (77°C); excursions are permitted between 15°C and 30°C (59°F and 86°F).
Alkalinizing Agents: May increase the serum concentration of Memantine. Monitor therapy
Benperidol: Memantine may diminish the therapeutic effect of Benperidol. Monitor therapy
BuPROPion: May increase the serum concentration of OCT2 Substrates. Monitor therapy
Carbonic Anhydrase Inhibitors: May increase the serum concentration of Memantine. Exceptions: Brinzolamide; Dorzolamide. Monitor therapy
NMDA Receptor Antagonists: May enhance the adverse/toxic effect of Memantine. 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. Monitor therapy
Adverse reactions similar in immediate and extended release formulations except as noted.
1% to 10%:
Cardiovascular: Hypertension (4%), hypotension (extended release: 2%)
Central nervous system: Dizziness (5% to 7%), confusion (6%), headache (6%), anxiety (extended release: 4%), depression (extended release: 3%), drowsiness (3%), hallucination (3%), pain (3%), aggressive behavior (2%), fatigue (2%)
Endocrine & metabolic: Weight gain (extended release: 3%)
Gastrointestinal: Diarrhea (5%), constipation (3% to 5%), vomiting (2% to 3%), abdominal pain (2%)
Genitourinary: Urinary incontinence (2%)
Infection: Influenza (4%)
Neuromuscular & skeletal: Back pain (3%)
Respiratory: Cough (4%), dyspnea (2%)
<1% (Limited to important or life-threatening): Anorexia, aspiration pneumonia, atrioventricular block, bone fracture, bradycardia, brain disease, bronchitis, cardiac failure, carpal tunnel syndrome, cerebral infarction, cerebrovascular accident, cholelithiasis, colitis, complete atrioventricular block, deep vein thrombosis, drug-induced Parkinson disease, fecal incontinence, gastritis, gastroesophageal reflux disease, hepatic failure, hepatitis (including cytolytic and cholestatic), hyperglycemia, hypoglycemia, increased INR, increased serum alkaline phosphatase, neuroleptic malignant syndrome, otitis media, pancreatitis, pancytopenia, peripheral edema, prolonged Q-T interval on ECG, psychotic reaction, renal failure, second-degree atrioventricular block, sepsis, SIADH, Stevens-Johnson syndrome, suicidal tendencies, supraventricular tachycardia, thrombotic thrombocytopenic purpura, tonic-clonic seizures, torsades de pointes, upper respiratory tract infection, urinary tract infection
Concerns related to adverse effects:
• Hypersensitivity: Rare skin hypersensitivity reactions (eg, Stevens Johnson syndrome, erythema multiforme) have been reported; advise patients to report skin reactions immediately. Discontinue use with signs of hypersensitivity reaction.
• 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. The Canadian labeling recommends avoiding use in severe impairment due to a lack of data in this population.
• 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 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.
• Urine pH: Clearance is significantly reduced by alkaline urine; use caution with medications, dietary changes, or patient conditions which may alter urine pH.
Cognitive function; periodic ophthalmic exam (Canadian labeling)
Pregnancy Risk Factor
Adverse events have been observed in animal reproduction studies.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache or constipation. Have patient report immediately to prescriber mood changes, depression, behavioral changes, seizures, severe dizziness, or passing out (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about memantine
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- Drug class: miscellaneous central nervous system agents
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