Generic Name: Memantine Hydrochloride
Class: Central Nervous System Agents, Miscellaneous
VA Class: CN900
Chemical Name: 3,5-Dimethyl-1-adamantanamine21
Molecular Formula: C12HN
CAS Number: 19982-08-2

Introduction

N-Methyl-d-aspartate (NMDA) receptor antagonist.1 2 3 4 5 6 7 8 9 10 11 12 13

Uses for Namenda

Alzheimer’s Disease

Palliative treatment of moderate to severe dementia of the Alzheimer’s type (Alzheimer’s disease).1 2

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Namenda Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.1

Administer dosages >5 mg daily in 2 divided doses.1

Administer oral solution using the oral dosing syringe and dosing device provided; follow the patient instructions provided by the manufacturer.1 Do not mix oral solution with any other liquids.1

Dosage

Available as memantine hydrochloride; dosage expressed in terms of memantine hydrochloride.1

Tablets and oral solution are equivalent on a mg-per-mg basis.15

Adults

Alzheimer’s Disease
Oral

Initially, 5 mg once daily for 1 week.1

Subsequently, increase dosage to 10 mg daily (5 mg twice daily) for ≥1 week, then 15 mg daily (administered as separate doses of 5 mg and 10 mg) for ≥1 week, and then to 20 mg daily (10 mg twice daily).1

Recommended target dosage: 20 mg daily given in 2 divided doses (10 mg twice daily).1

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1 (See Special Populations under Pharmacokinetics.)

Renal Impairment

No dosage adjustment needed in patients with mild to moderate renal impairment.1 In patients with severe renal impairment (i.e., Clcr 5–29 mL/minute), a target dosage of 5 mg twice daily is recommended.1 (See Special Populations under Pharmacokinetics.)

Geriatric Patients

No specific dosage adjustments at this time.1 (See Special Populations under Pharmacokinetics.)

Cautions for Namenda

Contraindications

  • Known hypersensitivity to memantine hydrochloride or any ingredient in the formulation.1

Warnings/Precautions

General Precautions

Seizures

Not systematically evaluated in patients with seizure disorders.1

Urinary Excretion

Conditions increasing urinary pH (e.g., dietary changes, concomitant use of drugs that alkalinize urine, renal tubular acidosis, severe urinary tract infections) may decrease memantine elimination and increase plasma concentrations and adverse effects; use with caution under these conditions.1 11 (See Alkalinizing Agents under Interactions and Elimination under Pharmacokinetics.)

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether memantine is distributed into human milk.1 Caution if used in nursing women.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

Efficacy studied principally in patients 50–93 (mean 76) years of age with moderate to severe Alzheimer’s disease.1 2 5 7 15 (See Special Populations under Pharmacokinetics.)

Hepatic Impairment

Not studied in patients with hepatic impairment.1 (See Special Populations under Pharmacokinetics.)

Renal Impairment

Increased exposure in patients with renal impairment.1 (See Renal Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Dizziness, confusion, headache, constipation.1 8

Interactions for Namenda

Minimally metabolized by CYP isoenzymes.1 Memantine produces minimal inhibition of isoenzymes 1A2, 2A6, 2C9, 2D6, 2E1, or 3A4 in vitro.1 No induction of isoenzymes 1A2, 2C9, 2E1, or A4/5 observed in vitro at concentrations exceeding those associated with therapeutic efficacy.1

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions unlikely.1 15

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions unlikely.1

Alkalinizing Agents

Potential decreased memantine clearance with resulting increases in adverse effects when the drug is used concomitantly with agents that increase urine pH.1 Use with caution.1

Protein-bound Drugs

Pharmacokinetic interaction with highly plasma protein-bound drugs is unlikely because memantine is only 45% bound to plasma proteins.1

Drugs Secreted by Renal Tubular Cationic Transport

Potential pharmacokinetic interaction (altered plasma concentrations of both drugs) when used with drugs secreted by the same renal cationic system.10

Specific Drugs

Drug

Interaction

Comments

Amantadine

Potential additive NMDA antagonistic effects1 8

Not systematically evaluated; use caution1

Carbonic anhydrase inhibitors

Potential decreased memantine clearance because of alkaline urine; possible increased incidence of adverse effects 1

Use with caution1

Cholinesterase inhibitors (e.g., donepezil, galantamine, tacrine)

Concomitant use with donepezil has been well tolerated1 13

Reversible inhibition of acetylcholinesterase not affected by memantine in vitro and in animals1 10

Cimetidine

Potential altered plasma concentrations of both drugs1

Dextromethorphan

Potential additive NMDA antagonistic effects1

Not systematically evaluated; use caution1

Digoxin

Pharmacokinetic interaction unlikely1

Hydrochlorothiazide (HCTZ)

Potential altered plasma concentrations of both drugs1

Maximum plasma HCTZ concentrations and AUCs decreased by 20% with concomitant use of memantine with fixed-combination of HCTZ and triamterene; memantine bioavailability unaffected 1 10

Ketamine

Potential additive NMDA antagonistic effects1

Not systematically evaluated; use caution1

Metformin

No effect on pharmacokinetics of memantine, metformin, or glyburide with concomitant use of memantine and fixed combination of glyburide and metformin hydrochloride; hypoglycemic effects of glyburide-metformin combination not affected1

Nicotine

Potential altered plasma concentrations of both drugs1

Quinidine

Potential altered plasma concentrations of both drugs1

Ranitidine

Potential altered plasma concentrations of both drugs1

Sodium bicarbonate

Potential decreased memantine clearance because of alkaline urine; possible increased incidence of adverse effects 1

Use with caution1

Triamterene

Potential altered plasma concentrations of both drugs1

Bioavailability of memantine or triamterene unaffected by concomitant use with triamterene (in fixed-combination with hydrochlorothiazide) 1 10

Warfarin

Pharmacokinetic interaction unlikely1

Namenda Pharmacokinetics

Absorption

Well absorbed following oral administration, with peak plasma concentrations attained in about 3–7 hours.1 4

Tablets and oral solution are equivalent on a mg-per-mg basis.15

Food

Food does not appear to affect absorption.1

Distribution

Extent

Not known whether memantine is distributed into human milk.1

Plasma Protein Binding

45%.1

Elimination

Metabolism

Undergoes limited metabolism, principally to 3 inactive metabolites; minimally metabolized by CYP isoenzymes.1

Elimination Route

Excreted principally in urine as unchanged drug (57–82%).1

Eliminated via active tubular secretion, moderated by pH-dependent tubular reabsorption. Clearance reduced by about 80% under alkaline urine conditions (urine pH of 8).

Half-life

Terminal half-life is approximately 60–80 hours.1

Special Populations

In patients with hepatic impairment, only a modest effect on clearance is expected.1

Renal impairment increases exposure.1 AUC increased by 4, 60, or 115% in individuals with mild (Clcr >50 but <80 mL/minute), moderate (Clcr 30–49 mL/minute), or severe (Clcr 5–29 mL/minute) renal impairment, respectively.1 Terminal elimination half-life increased by 18, 41, or 95% in those with mild, moderate, or severe renal impairment, respectively.1 (See Renal Impairment under Dosage and Administration and under Cautions.)

In geriatric patients, pharmacokinetics similar to those in younger adults.1

Stability

Storage

Oral

Tablets and Oral Solution

25°C (may be exposed to 15-30°C).1

Actions

  • Low- to moderate-affinity, noncompetitive NMDA receptor antagonist; binds preferentially to NMDA receptor-operated cation channels.1 3 4 5 6 7 8 9 10 11 12

  • Differs structurally and pharmacologically from other currently available agents used for the palliative treatment of Alzheimer’s disease.1 2

  • May act by blocking actions of glutamate (principal CNS excitatory neurotransmitter), which are mediated in part by NMDA receptors.1 2 3 5 6 7 9

  • Persistent NMDA receptor activation by glutamate may cause neurodegeneration in various types of dementia and may contribute to Alzheimer’s disease symptomatology.1 3 5 6

  • Low- to moderate-affinity NMDA receptor antagonists may prevent glutamate-induced neurotoxicity without interfering with NMDA receptor-mediated physiologic processes.3 6 7 12

  • Currently no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer’s disease.1

  • Does not affect reversible inhibition of acetylcholinesterase produced by donepezil, galantamine, or tacrine in vitro.1

Advice to Patients

  • Importance of instructing caregiver regarding proper administration (divide dosages >5 mg daily into 2 separate doses) and dosage escalation (≥1 week between dosage increases).1

  • Importance of instructing patients and/or caregivers in proper use of oral syringe and dosing device provided with oral solution.1 Ensure that patients and/or caregivers are aware of the patient instruction sheet enclosed with the solution.1 Oral solution should not be mixed with any other liquids.1 Advise that questions about administration should be directed to their pharmacist or clinician.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Memantine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

10 mg/5 mL

Namenda (with parabens and propylene glycol)

Forest

Tablets, film-coated

5 mg

Namenda

Forest

10 mg

Namenda

Forest

5 mg (28 tablets) and 10 mg (21 tablets)

Namenda Titration Pak

Forest

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Namenda 10MG Tablets (FOREST): 60/$240.84 or 180/$673.93

Namenda 5MG Tablets (FOREST): 60/$240.00 or 120/$462.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Forest Pharmaceuticals, Inc. Namenda (memantine hydrochloride) tablets and oral solution prescribing information. St. Louis, MO; 2005 Jul.

2. Tariot PN, Farlow MR, Grossberg GT et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil. JAMA. 2004; 291:317-24. [IDIS 510229] [PubMed 14734594]

3. Doraiswamy PM. Non-cholinergic strategies for treating and preventing Alzheimer’s disease. CNS Drugs. 2002; 16:811-24. [PubMed 12421115]

4. Jarvis B, Figgitt DP. Memantine. Drugs Aging. 2003; 20:465-76. [PubMed 12710865]

5. Reisberg B, Doody R, Stöffler A et al. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med. 2003; 348: 1333-41.

6. Scarpini E, Scheltens P, Feldman H. Treatment of Alzheimer’s disease: current status and new perspectives. Lancet Neurol. 2003; 2:539-47. [PubMed 12941576]

7. Anon. Alzheimer’s disease: emerging noncholinergic treatments. Geriatrics. 2003; 58 (Suppl):3-14, inside cover. [IDIS 492749] [PubMed 12599937]

8. Anon. Memantine for Alzheimer’s disease. Med Lett Drugs Ther. 2003; 45:73-4. [PubMed 12968123]

9. Feret B, Dicks R. Memantine. Formulary. 2004; 39:91-103.

10. Cada DJ, Levien T, Baker DE. Memantine. Hosp Pharm. 2004; 39:254-63.

11. Anon. Memantine for dementia?. Drug Ther Bull. 2003; 41:73-6. [PubMed 14593973]

12. Areosa SA, Sherriff F. Memantine for dementia. Cochrane Database Syst Rev. 2003; 3:CD003154. [PubMed 12917950]

13. Periclou AP, Ventura D, Sherman T et al. Lack of pharmacokinetic or pharmacodynamic interaction between memantine and donepezil. Ann Pharmacother. 2004; 38:1389-94. [IDIS 528906] [PubMed 15266045]

14. Reisberg B, Ferris S, Möbius HJ et al. Long-term treatment with the NDMA antagonist memantine: results of a 24-week, open-label extension study in moderately severe-to-severe Alzheimer’s disease [abstract]. Neurobiol Aging. 2002; 23:S555, abst 2039.

15. Forest Laboratories, New York, NY. Personal communication.

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