Memantine - Index

All criteria may be applied retrospectively and each set identifies prospective application is indicated with an asterisk [*]. The information contained is for the convenience of the public. The Texas Health and Human Services Commission is not responsible for any errors in transmission or any errors or omissions in the document.

  • Revision history
    • July 21, 2023
    • July 23, 2021
    • May 2019
    • May 2017
    • Nov. 2015
    • March 2014
    • March 2012
  • Initially developed
    • April 2010

1.1. Adults

Memantine, a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist, is FDA-approved for use in the palliative management of moderate-to-severe Alzheimer’s disease. Glutamate, the key excitatory neurotransmitter in the central nervous system, is released into synapses when certain neurons die and activates NMDA receptors, causing over excitation, an influx of calcium ions and, ultimately, death of downstream neurons. NMDA receptor activation is thought to be one of the main causes of neurodegeneration in various types of dementia, including Alzheimer’s-associated dementia. Memantine exerts pharmacologic effects by binding to NMDA receptors thus blocking activation by glutamate. However, memantine has not been shown to delay or prevent neurodegeneration in Alzheimer’s disease patients1-4.

Memantine is available as an immediate-release (IR) tablet and solution as well as extended-release (ER) capsule. A combination product containing donepezil and memantine extended-release (Namzaric®) is also available for use in patients with moderate to severe Alzheimer’s dementia stabilized on donepezil. Acetylcholinesterase inhibitors like donepezil exert pharmacologic effects by increasing availability of intrasynaptic acetylcholine in the presence of intact cholinergic neurons. Alzheimer’s disease is associated with significant losses in cholinergic neurons and decreased concentrations of acetylcholine, a neurotransmitter significantly involved in learning and memory processes.

Recommended memantine and memantine/donepezil dosages are summarized in Table 1. Patient profiles documenting dosages exceeding these recommendations will be reviewed.

In patients with severe renal impairment (creatinine clearance 5-29 mL/min, based on Cockcroft-Gault equation), the memantine target IR dose should be reduced to 5 mg orally twice daily, while memantine ER maximum dosages should not exceed 14 mg once daily. Patients with severe renal impairment (CrCl 5-29 mL/min) stabilized on memantine 5 mg twice daily immediate-release or 14 mg daily extended-release and donepezil 10 mg daily may utilize memantine/donepezil combination therapy in doses not exceeding 14 mg/10 mg daily.

Table 1. Approved Memantine Adult Dosage Recommendations: Monotherapy
Drug Name Dosage Form/Strength Titration Dose ^ Maximum Recommended Dosage
memantine IR* (Namenda®) 5 mg, 10 mg tablets
2 mg/ml oral solution
Week 1: 5 mg orally once daily
Week 2: 5 mg orally twice daily
Week 3: 10 mg in am, 5 mg in pm
Week 4: 10 mg orally twice daily 
20 mg/day, in divided doses
memantine ER+ (Namenda XR®) 7 mg, 14 mg, 21 mg, 28 mg capsules Week 1: 7 mg orally once daily
Week 2: 14 mg orally once daily
Week 3: 21 mg orally once daily
Week 4: 28 mg orally once daily
28 mg/day as a single dose

Legend:

  • *IR = immediate-release
  • +ER = extended-release
  • ^Titrate in weekly intervals to next dose, only if previous dose tolerated
Table 2. Approved Memantine Adult Dosage Recommendations: Combination Therapy
Drug Name Dosage Form/Strength Titration Dose^ Maximum Recommended Dosage
memantine extended-release/donepezil (Namzaric®) 7 mg/10 mg, 14 mg/ 
10 mg, 21 mg/ 10 mg, 
28 mg/ 10 mg capsules
  • Week 1: 7 mg/ 10 mg orally once daily
  • Week 2: 14 mg/ 10 mg orally once daily
  • Week 3: 21 mg/ 10 mg orally once daily
  • Week 4: 28 mg/ 10 mg orally once daily*
28 mg/10 mg once daily

Legend:

  • ^ Titrate in weekly intervals to next dose, only if previous dose tolerated
  • * Titration schedule indicated for patients who are stabilized on donepezil and not currently on memantine

While Tariot et al. have shown beneficial improvements in cognitive and behavioral performance when memantine is administered in combination with donepezil, a recent trial by Howard and cohorts and systematic review by Tricco et al. revealed that monotherapy with memantine or donepezil was significantly better than no therapy, but combined therapy did not produce significant improvements in cognitive and functional outcomes compared to donepezil alone. Although not FDA-approved, memantine therapy has demonstrated some efficacy in treating mild-to-moderate vascular dementia and Parkinson’s disease dementia. Memantine has been approved as an extended-release formulation to simplify the dosage regimen and improve compliance/adherence.

1.2. Pediatrics

Memantine is not recommended for use in children and adolescents as safety and efficacy have not been established in the pediatric population.

2. Duration of Therapy

Memantine may be prescribed chronically until the dementia associated with Alzheimer’s disease becomes unresponsive to therapy.

3. Duplicative Therapy

Adjunctive administration of memantine with other NMDA antagonists, such as amantadine and dextromethorphan, has not been clinically evaluated. Therefore, memantine should be prescribed cautiously, if at all, with other available NMDA antagonists. 

4. Drug-Drug Interactions

Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for memantine are summarized in Table 3. Only those drug-drug interactions identified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.

Table 3. Memantine Drug-Drug Interactions
Target Drug Interacting Drug Interaction Recommendation Clinical Significance Level #
memantine, memantine/ donepezil alkalinizing agents (e.g., select carbonic anhydrase inhibitors, sodium bicarbonate) memantine clearance reduced by about 80% in alkaline conditions (pH greater than or equal to 8); adjunctive administration with alkalinizing agents may decrease memantine elimination and increase memantine serum levels and potential for increased pharmacologic/adverse effects administer drug combination cautiously together; monitor patients for increased pharmacologic/adverse effects 3-moderate (CP)
memantine, memantine/ donepezil other drugs excreted by renal tubular secretion (e.g., amiloride, cimetidine, dofetilide, nicotine, quinidine, ranitidine) memantine eliminated by renal tubular cationic transport; combined administration may result in altered serum levels of both memantine and other drugs excreted by renal tubular secretion due to competition for transport system; elevated dofetilide levels may increase potential for arrhythmias, including torsades de pointes monitor patient responses, observe for adverse effects or loss of efficacy, and adjust doses as necessary dofetilide, procainamide, quinidine: 2-major; all other drugs: 3-moderate (CP)

Legend:

  • #CP = Clinical Pharmacology

5. References

  1. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2023. Available at: http://clinicalpharmacology-ip.com.ezproxy.lib.utexas.edu/. Accessed May 31, 2023.
  2. IBM Micromedex® DRUGDEX® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www-micromedexsolutions-com.libproxy.uthscsa.edu/ (cited: May 31, 2023).
  3. Memantine tablets/oral solution (Namenda®) package insert. Allegan USA, Inc., November 2018.
  4. Memantine extended-release capsules (Namenda XR®) package insert. Allergan USA, Inc., November 2019.
  5. Memantine and donepezil extended-release capsules (Namzaric®) package insert. Allergan USA, Inc., January 2019.
  6. Tariot PN, Farlow MR, Grossberg GT, et al, for the Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291:317-24.
  7. Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med. 2012;366:893-903.
  8. Tricco AC, Ashoor HM, Soobiah C, et al. Comparative effectiveness and safety of cognitive enhancers for treating Alzheimer’s disease: systematic review and network metaanalysis. J Am Geriatr Soc. 2018;66(1):170–8.
  9. Emre M, Tsolaki M, Bonuccelli U, et al.  Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9:969–77.
  10. Leroi I, Overshott R, Byrne EJ, et al.  Randomized controlled trial of memantine in dementia associated with Parkinson's disease.  Mov Disord. 2009;24(8):1217-21.