Medically reviewed by Drugs.com. Last updated on Jul 27, 2020.
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- Memantine HCl
- Memantine Hydrochloride
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
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)
Generic: 7 mg, 14 mg, 21 mg, 28 mg
Solution, Oral, as hydrochloride:
Namenda: 10 mg/5 mL (360 mL [DSC])
Generic: 2 mg/mL (240 mL, 360 mL); 10 mg/5 mL (5 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 (NMDA) 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
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, moderate to severe: Treatment of moderate to severe dementia of the Alzheimer type.
Off Label Uses
Dementia (ie, Parkinson disease–related dementia, dementia with Lewy bodies, vascular dementia)
Data from meta-analyses evaluating 2 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 [Kavirajan 2007], [McShane 2019]. Data from a randomized, double-blind, placebo-controlled study suggest that memantine may be beneficial for the treatment of Parkinson disease–related dementia [Aarsland 2009]. Data from a randomized, double-blind, placebo-controlled study suggest that memantine may be beneficial for dementia with Lewy bodies [Emre 2010].
Based on the National Institute for Health and Care Excellence (NICE) guideline for the assessment, management, and support for people living with dementia and their carers, memantine should only be considered for vascular dementia in patients with suspected comorbid Alzheimer disease, Parkinson disease dementia, or dementia with Lewy bodies [NICE 2018]. Similarly, the British Association for Psychopharmacology (BAP) consensus statement on clinical practice with anti-dementia drugs suggests that memantine should not be used for vascular dementia unless mixed vascular dementia and Alzheimer disease is suspected [BAP [O'Brien 2017]]. As for dementia with Lewy bodies and Parkinson disease dementia, the NICE guidelines on dementia and Parkinson disease in adults recommend using memantine only if acetylcholinesterase inhibitors are not tolerated or are contraindicated, while the BAP consensus statement suggests that memantine may be helpful for dementia with Lewy bodies and Parkinson disease dementia [BAP [O'Brien 2017]], [NICE 2017], [NICE 2018].
Neurocognitive toxicity of whole brain irradiation, prevention
Data from a randomized, double-blind, placebo-controlled study suggest that memantine may be beneficial for preserving cognitive function (eg, memory) after whole brain irradiation. Memantine was associated with less decline in delayed recall at 24 weeks; however, the data lacked statistical significance due to patient loss [Brown 2013].
Hypersensitivity to memantine or any component of the formulation
Alzheimer disease, moderate to severe (monotherapy or in combination with a cholinesterase inhibitor):
Immediate release: Initial: 5 mg once daily; increase daily dose by 5 mg every week as tolerated to a target maximum dose of 20 mg/day. Note: Dose may be administered once daily or in 2 divided doses (Howard 2012; Jones 2007; Porsteinsson 2008).
Extended release: Initial: 7 mg once daily; increase daily dose by 7 mg every week as tolerated to a target maximum dose of 28 mg once daily (Grossberg 2013).
Dementia (ie, Parkinson disease–related dementia, dementia with Lewy bodies, vascular dementia) (monotherapy or in combination with a cholinesterase inhibitor) (off-label use):
Oral: Immediate release: Initial: 5 mg once daily; increase dose by 5 mg every week as tolerated to a target maximum dose of 20 mg/day. Note: Dose may be administered once daily or in 2 divided doses (Aarsland 2009; Emre 2010; Wilcock 2002).
Neurocognitive toxicity of whole brain irradiation, prevention (off-label use):
Immediate release: Initial: 5 mg once daily with the initiation of radiation; increase dose by 5 mg weekly as tolerated to a target maximum dose of 20 mg/day. Doses >5 mg/day may be given in 2 divided doses. Continue for up to 6 months after completion of whole brain radiation therapy (WBRT) (Brown 2013; Brown 2020).
Extended release: Initial: 7 mg once daily with the initiation of radiation; increase dose by 7 mg weekly as tolerated to a target maximum dose of 28 mg once daily. Continue for up to 6 months after completion of WBRT (Brown 2020).
Discontinuation of therapy: Discontinuation of therapy may result in worsening of cognitive function. Avoid abrupt discontinuation except in the case of severe adverse drug reaction to minimize withdrawal symptoms (eg, altered mental status, hallucinations, delusions, insomnia, increased anxiety and agitation). In general, memantine should be tapered using a 50% dose reduction or stepwise reduction via available dose formulations every 4 weeks to the lowest dose prior to discontinuation. Consider re-initiation if clear worsening of the condition occurs after withdrawal (Reeve 2019).
Conversion from immediate release to extended release: Begin the ER product the day after the last dose of the IR product.
If current IR dose is 10 mg/day: Convert to ER capsule 14 mg once daily.
If current IR dose is 20 mg/day: Convert to ER capsule 28 mg once daily.
Missed doses: If several days of dosing are missed with either formulation, dosing may need to be resumed at lower doses and retitrated.
Refer to adult dosing.
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°F); 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
Carbonic Anhydrase Inhibitors: May increase the serum concentration of Memantine. Monitor therapy
Erdafitinib: May increase the serum concentration of OCT2 Substrates. Monitor therapy
NMDA Receptor Antagonists: May enhance the adverse/toxic effect of Memantine. Monitor therapy
Tafenoquine: May increase the serum concentration of OCT2 Substrates. Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling. Consider therapy modification
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
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Adverse reactions similar in immediate and extended release formulations except as noted.
1% to 10%:
Cardiovascular: Hypertension (4%), hypotension (ER: 2%)
Endocrine & metabolic: Weight gain (ER: 3%)
Gastrointestinal: Abdominal pain (ER: 2%), constipation (3% to 5%), diarrhea (ER: 5%), vomiting (2% to 3%)
Genitourinary: Urinary incontinence (ER: 2%)
Nervous system: Aggressive behavior (ER: 2% [placebo: 1%]), anxiety (ER: 4% [placebo: 3%]), confusion (IR: 6% [placebo: 5%]), depression (ER: 3% [placebo: 1%]), dizziness (5% to 7% [placebo: 1% to 5%]), drowsiness (3% [placebo: 1%]), fatigue (IR: 2% [placebo: 1%]), hallucination (IR: 3% [placebo: 2%]), headache (6% [placebo: 3% to 5%]), pain (IR: 3% [placebo: 1%])
Neuromuscular & skeletal: Back pain (3%)
Respiratory: Cough (IR: 4%), dyspnea (IR: 2%)
Cardiovascular: Bradycardia (rare: <1%) (Gallini 2008), cardiac failure (rare: <1%) (Gallini 2008), prolonged QT interval on ECG (rare: <1%) (Kajitani 2016; Takehara 2015)
Dermatologic: Stevens-Johnson syndrome (rare: <1%)
Gastrointestinal: Pancreatitis (rare: <1%)
Hematologic & oncologic: Agranulocytosis (rare: <1%), leukopenia (including neutropenia) (rare: <1%), pancytopenia (rare: <1%), thrombocytopenia (rare: <1%), thrombotic thrombocytopenic purpura (rare: <1%)
Hepatic: Cholestatic hepatitis (rare: <1%) (Ferrara 2008)
Hypersensitivity: Fixed drug eruption (rare: <1%) (Saito 2017)
Nervous system: Agitation (rare: <1%) (Monastero 2007; Ridha 2005), delusion (rare: <1%) (Monastero 2007; Ridha 2005), loss of consciousness (rare: <1%) (Savic 2013), mania (rare: <1%) (Duan 2018), seizure (rare: <1%) (Peltz 2005), suicidal ideation (rare: <1%)
Renal: Acute renal failure (rare: <1%) (Horikawa 2013; Tsukamoto 2013)
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 for CrCl <30 mL/minute is 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; functional outcomes (eg, Activities of Daily Living [ADLs], Instrumental Activities of Daily Living [IADLs]); periodic ophthalmic exam (Canadian labeling)
Adverse events have been observed in animal reproduction studies.
What is this drug used for?
• It is used to treat dementia in people with Alzheimer's disease.
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
More about memantine
- Side Effects
- During Pregnancy
- Dosage Information
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- En Español
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- Drug class: miscellaneous central nervous system agents
- Memantine (AHFS Monograph)
- Memantine ER Tablets (FDA)
- Memantine ER capsules (FDA)
- Memantine Oral Solution (FDA)
- Memantine Tablets (FDA)
- Memantine (FDA)