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Memantine

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

Medically reviewed by Drugs.com on Oct 19, 2020. Written by ASHP.

Introduction

N-Methyl-d-aspartate (NMDA) receptor antagonist.

Uses for Memantine

Alzheimer’s Disease

Management of moderate to severe dementia of the Alzheimer’s type (Alzheimer’s disease).

Provides only modest benefits in patients with moderate to severe disease. Because of some benefit and lack of adverse effects, experts state that memantine may be considered (alone or in combination with a cholinesterase inhibitor) in patients with moderate to severe Alzheimer's disease.

Has been used in patients with mild Alzheimer's disease; however, studies generally have not found a benefit for milder forms of the disease.

May be used in combination with a cholinesterase inhibitor (e.g., donepezil, galantamine, rivastigmine). A fixed-combination preparation containing memantine and donepezil is commercially available for the treatment of moderate to severe Alzheimer's disease in patients currently receiving donepezil hydrochloride at a stable dosage of 10 mg once daily. The addition of memantine to established therapy with a cholinesterase inhibitor may result in less clinical deterioration than therapy with a cholinesterase inhibitor alone in patients with moderate to severe Alzheimer's disease, but the effect size appears to be small and of uncertain clinical importance.

Autism Spectrum Disorders

Has been evaluated as a potential treatment in children with autism spectrum disorders. However, efficacy not established for this use; clinical studies generally have found no difference with the drug compared with placebo in core symptoms of autism.

Memantine Dosage and Administration

Administration

Oral Administration

Administer orally (as tablets, oral solution, or extended-release capsules) without regard to meals.

Tablets and oral solution are bioequivalent.

Oral solution: Administer using the oral dosing syringe provided by manufacturer. Do not mix oral solution with any other liquids.

Extended-release capsules: Swallow capsules intact (do not divide, chew, or crush); alternatively, may open capsules, sprinkle on applesauce, and swallow without chewing. Consume entire contents of capsule; do not divide dose.

Fixed-combination preparation containing memantine hydrochloride and donepezil hydrochloride (Namzaric): Swallow capsules intact (do not divide, chew, or crush); alternatively, may open capsules, sprinkle on applesauce, and swallow without chewing. Consume entire contents of capsule; do not divide dose.

If a dose is missed, take next dose as scheduled; do not double dose to make up for a missed dose. If treatment is interrupted for several days, may need to restart with a lower dosage and retitrate.

Dosage

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

Adults

Alzheimer’s Disease
Tables and Oral Solution
Oral

Initially, 5 mg once daily.

Increase dosage by increments of 5 mg daily at intervals of ≥1 week to recommended maintenance dosage of 10 mg twice daily; this can be achieved by increasing 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).

Effective dosage in controlled clinical trials was 10 mg twice daily.

Extended-release Capsules
Oral

Initially, 7 mg once daily.

Increase dosage by increments of 7 mg daily at intervals of ≥1 week, if well tolerated, to recommended maintenance dosage of 28 mg once daily.

Effective dosage in controlled clinical trials was 28 mg once daily.

Patients currently receiving memantine hydrochloride tablets or oral solution at a dosage of 10 mg twice daily may be switched to the extended-release capsules at a dosage of 28 mg once daily; the transition should occur on the day following the last dose of the conventional preparation.

Fixed-combination Memantine and Donepezil Extended-release Capsules (Namzaric)
Oral

Patients stabilized on donepezil hydrochloride 10 mg daily and not currently on memantine who are switching to the fixed-combination preparation: Recommended initial dosage is 7 mg of memantine hydrochloride and 10 mg of donepezil hydrochloride once daily in the evening. May increase dosage in increments of 7 mg of the memantine hydrochloride component at minimum intervals of ≥1 week up to maximum recommended maintenance dosage of 28 mg of memantine hydrochloride and 10 mg of donepezil hydrochloride once daily in the evening.

Patients switching from separate donepezil and memantine preparations (i.e., donepezil hydrochloride 10 mg daily; memantine hydrochloride 10 mg twice daily or 28 mg once daily as the extended-release preparation) to the fixed-combination preparation: Recommended dosage is 28 mg of memantine hydrochloride and 10 mg of donepezil hydrochloride once daily in the evening. Initiate therapy with the fixed-combination preparation on the day following the last dose of the individual preparations.

Prescribing Limits

Adults

Alzheimer's Disease
Oral

Tablets or oral solution: 10 mg twice daily (or 5 mg twice daily in patients with severe renal impairment).

Extended-release capsules: Maximum of 28 mg once daily (or 14 mg once daily in patients with severe renal impairment).

Special Populations

Hepatic Impairment

No dosage adjustment needed in patients with mild to moderate hepatic impairment. Use with caution in patients with severe hepatic impairment. (See Special Populations under Pharmacokinetics.)

Renal Impairment

No dosage adjustment needed in patients with mild to moderate renal impairment. In patients with severe renal impairment (i.e., Clcr 5–29 mL/minute), a target dosage of 5 mg twice daily (as conventional preparations) or 14 mg once daily (as extended-release capsules) is recommended. (See Special Populations under Pharmacokinetics.)

Geriatric Patients

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

Cautions for Memantine

Contraindications

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

Warnings/Precautions

General Precautions

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. (See Alkalinizing Agents under Interactions and Elimination under Pharmacokinetics.)

Specific Populations

Pregnancy

No adequate data on developmental risks associated with use in pregnant women. In animal reproduction studies, adverse developmental effects (e.g., decreased body weight, decreased skeletal ossification) observed.

Lactation

Not known whether memantine is distributed into milk or if the drug affects the nursing infant or milk production. Consider known benefits of breast-feeding along with the mother's need for memantine and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy in pediatric patients not established.

Has been evaluated in children 6–12 years of age with autism spectrum disorders (ASD); however, efficacy not demonstrated. (See Autism Spectrum Disorders under Uses.)

Geriatric Use

No clinically important differences in adverse effects observed between geriatric patients and younger adults. (See Special Populations under Pharmacokinetics.)

Hepatic Impairment

No effect of moderate hepatic impairment (Child-Pugh class B) on exposure of memantine.

Not evaluated in patients with severe hepatic impairment; use with caution.

Renal Impairment

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

Common Adverse Effects

Conventional preparations: Dizziness, confusion, headache, constipation.

Extended-release capsules: Headache, diarrhea, dizziness.

Interactions for Memantine

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

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions unlikely.

Alkalinizing Agents

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

Protein-bound Drugs

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

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.

Specific Drugs

Drug

Interaction

Comments

Amantadine

Potential additive NMDA antagonistic effects

Not systematically evaluated; use caution

Bupropion

Pharmacokinetics of bupropion and its hydroxy metabolite not affected

Carbonic anhydrase inhibitors

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

Use concomitantly with caution

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

Concomitant use with donepezil has been well tolerated; pharmacokinetics of either drug not affected

Reversible inhibition of acetylcholinesterase not affected by memantine in vitro and in animals

Cimetidine

Potential altered plasma concentrations of both drugs

Dextromethorphan

Potential additive NMDA antagonistic effects

Not systematically evaluated; use caution

Digoxin

Pharmacokinetic interaction unlikely

Hydrochlorothiazide (HCTZ)

Potential altered plasma concentrations of both drugs

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

Ketamine

Potential additive NMDA antagonistic effects

Not systematically evaluated; use caution

Metformin

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

Nicotine

Potential altered plasma concentrations of both drugs through renal transporter-mediated interaction

Quinidine

Potential altered plasma concentrations of both drugs through renal transporter-mediated interaction

Ranitidine

Potential altered plasma concentrations of both drugs through renal transporter-mediated interaction

Sodium bicarbonate

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

Use concomitantly with caution

Triamterene

Potential altered plasma concentrations of both drugs

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

Warfarin

Pharmacokinetic interaction unlikely

Memantine Pharmacokinetics

Absorption

Well absorbed following oral administration of conventional preparations, with peak plasma concentrations attained in about 3–7 hours.

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

Following multiple-dose administration of extended-release capsules, peak concentrations achieved in about 9–12 hours.

Food

Food does not appear to affect absorption.

Distribution

Extent

Not known whether memantine is distributed into human milk.

Plasma Protein Binding

45%.

Elimination

Metabolism

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

Elimination Route

Excreted principally in urine as unchanged drug (about 48%).

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.

Special Populations

In patients with moderate hepatic impairment (Child-Pugh class B), no change in memantine exposure observed; however, terminal half-life was increased by about 16%. Pharmacokinetics not evaluated in patients with severe hepatic impairment.

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

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

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).

Extended-release Capsules

25°C (may be exposed to 15–30°C).

Oral Solution

20–25°C.

Fixed-combination Memantine and Donepezil Extended-release Capsules

20–25°C (may be exposed to 15–30°C).

Actions

  • Low- to moderate-affinity, noncompetitive NMDA receptor antagonist; binds preferentially to NMDA receptor-operated cation channels.

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

  • May act by blocking actions of glutamate (principal CNS excitatory neurotransmitter), which are mediated in part by NMDA receptors.

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

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

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

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

Advice to Patients

  • Importance of instructing patients and/or caregivers regarding proper dosing and administration of memantine.

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

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

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

  • 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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Memantine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release

7 mg*

Memantine Hydrochloride Extended-release Capsules

Namenda XR

Allergan

14 mg*

Memantine Hydrochloride Extended-release Capsules

Namenda XR

Allergan

21 mg*

Memantine Hydrochloride Extended-release Capsules

Namenda XR

Allergan

28 mg*

Memantine Hydrochloride Extended-release Capsules

Namenda XR

Allergan

Solution

10 mg/5 mL*

Memantine Hydrochloride Solution

Tablets, film-coated

5 mg*

Memantine Hydrochloride Tablets

Namenda

Allergan

10 mg*

Memantine Hydrochloride Tablets

Namenda

Allergan

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

Namenda Titration Pak

Allergan

Memantine Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release

7 mg with Donepezil Hydrochloride 10 mg

Namzaric

Allergan

14 mg with Donepezil Hydrochloride 10 mg

Namzaric

Allergan

21 mg with Donepezil Hydrochloride 10 mg

Namzaric

Allergan

28 mg with Donepezil Hydrochloride 10 mg

Namzaric

Allergan

AHFS DI Essentials™. © Copyright 2021, Selected Revisions October 19, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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