Texas Health and Human Services Commission
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Criteria for Outpatient Use Guidelines

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Memantine (Namenda®)

[Developed, April 2010]

Information on indications for use or diagnosis is assumed to be unavailable. All criteria may be applied retrospectively; prospective application is indicated with [*].

* Dosage

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 overexcitation, 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 blocking glutamate activity. However, memantine has not been shown to delay or prevent neurodegeneration in Alzheimer’s disease patients.

The recommended initial adult memantine dose is 5 mg daily orally. This dose should be titrated slowly over 1-week intervals in increments of 5 mg for a period of three weeks to reach a target dose of 10 mg orally twice daily by week 4 (e.g., week 1: 5 mg orally once daily; week 2: 5 mg orally twice daily; week 3: 10 mg orally in am and 5 mg in pm; week 4 and subsequent weeks: 10 mg orally twice daily). In patients with severe renal impairment, the memantine target dose should be reduced to 5 mg orally twice daily. Memantine is available as a 5 mg and 10 mg tablet, as well as a 10 mg/5 ml oral solution.

While not FDA-approved, memantine has shown beneficial improvements in cognitive and behavioral performance when administered in combination with donepezil, and has also demonstrated some efficacy in treating mild-to-moderate vascular dementia.

Pediatrics

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

Duration of Therapy

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

*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.

*Drug-Drug Interactions

Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions.
The following drug-drug interactions are considered clinically relevant for memantine. 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:

a. Alkalinizing Agents (e.g., carbonic anhydrase inhibitors, sodium bicarbonate) [clinical significance level –moderate (Clinical Pharmacology); moderate (DrugReax)]Memantine clearance is reduced by approximately 80% in alkaline urine conditions (i.e., pH 8). Concurrent administration of memantine with alkalinizing agents may result in reduced memantine elimination and the potential for increased memantine serum concentrations and enhanced pharmacologic/adverse effects. Therefore, memantine should be administered cautiously with drugs known to increase urinary pH, and patients should be monitored for increased memantine adverse effects if this drug combination is utilized.

b. Dofetilide (Tikosyn®) [clinical significance level – severe (Clinical Pharmacology)] Both memantine and dofetilide are eliminated by renal tubular cationic transport. Concurrent administration of memantine and dofetilide may result in increased dofetilide concentrations and the potential for arrhythmias, including torsades de pointes, due to competition for renal elimination. Adjunctive administration of memantine and dofetilide is not recommended by the dofetilide manufacturer and will be reviewed.

REFERENCES

  1. AHFS Drug Information 2010 [book online]. Jackson, WY: Teton Data Systems, Version 6.7.1, 2009. Based on: McEvoy GK, editor. AHFS drug information 2010. Bethesda (MD): American Society of Health-System Pharmacists; 2010. Stat!Ref Electronic Medical Library.
  2. Drug Facts and Comparisons. Clin-eguide [database online]. St. Louis, MO: Wolters Kluwer Health, Inc; 2010. Available at: http://clineguide.com. Accessed April 9th, 2010.
  3. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc; 2010. Available at: http://www.clinicalpharmacology.com. Accessed April 9th, 2010.
  4. Memantine (Drug Evaluation). In: DRUGDEX® System (electronic version). Thomson Reuters (Healthcare) Inc., Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com.libproxy.uthscsa.edu. Accessed April 9th, 2010.
  5. Drug treatment of dementia due to Alzheimer’s disease. Pharmacist’s Letter/Prescriber’s Letter. 2006;22(10):221005.
  6. Memantine (Namenda®) package insert. Forest Pharmaceuticals, Inc., April 2007.
  7. Dofetilide (Tikosyn®) package insert. Pfizer Inc., November 2006.
  8. Reisberg B, Doody R, Stoffler A, et al, for the Memantine Study Group. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med. 2003;348:1333-41.
  9. 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.
  10. Reisberg B, Doody r, Stoffler A, et al. a 24-week open-label extension study of memantine in moderate to severe Alzheimer disease. Arch Neurol. 2006;63:49-54.
  11. Farlow MR, Cummings JL. Effective pharmacologic management of Alzheimer’s disease. Am J Med. 2007;120:388-97.
  12. Shah RS, Lee HG, Xiongwei Z, et al. Current approaches in the treatment of Alzheimer’s disease. Biomed Pharmacother. 2008;62:199-207.
  13. Cummings JL, Mackell J, Kaufer D. Behavioral effects of current Alzheimer’s disease treatments: a descriptive review. Alzheimers Dement. 2008;4:49-60.

Prepared by: Drug Information Service, The University of Texas Health Science Center at San Antonio, and the College of Pharmacy, The University of Texas at Austin.