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Memantine Hydrochloride

Pronunciation: me-MAN-teen HYE-droe-KLOR-ide
Class: NMDA receptor antagonist

Trade Names

- Tablets 5 mg
- Tablets 10 mg
- Solution, oral 2 mg/mL

Namenda XR
- Capsules, ER 7 mg
- Capsules, ER 14 mg
- Capsules, ER 21 mg
- Capsules, ER 28 mg

Ebixa (Canada)


It is postulated that memantine exerts its therapeutic effect as a low to moderate affinity uncompetitive nervous system N-methyl-D-aspartate (NMDA) receptor antagonist by binding preferentially to the NMDA receptor–operated cation channels.



Well absorbed from the GI tract; T max is approximately 3 to 7 h (immediate release) and 9 to 12 h (ER).


Vd is 9 to 11 L/kg. Plasma protein binding is 45%.


Little metabolism with 57% to 82% excreted unchanged in the urine and remainder eliminated as 3 polar metabolites that possess minimal activity.


Terminal elimination half-life is approximately 60 to 80 h. Renal elimination involves active tubular secretion moderated by pH-dependent tubular reabsorption.

Special Populations

Renal Function Impairment

Mean AUC 0-∞ 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.

Hepatic Function Impairment

Terminal elimination half-life increased by approximately 16% in patients with moderate hepatic impairment. Pharmacokinetics of memantine have not been evaluated in patients with severe hepatic impairment.


Pharmacokinetics similar in younger and elderly patients.


Women had approximately 45% greater exposure than men; however, there was no difference in exposure when body weight was taken into account.

Indications and Usage

Treatment of moderate to severe dementia of the Alzheimer type.

Unlabeled Uses

Attention deficit hyperactivity disorder; postherpetic neuralgia; prevention of migraine in adults; treatment of vascular dementia.


None well documented.

Dosage and Administration

Adults Immediate Release

PO Start with 5 mg daily. Increase the dose in 5 mg increments to 5 mg twice daily, 15 mg/day (5 and 10 mg as separate doses), and 10 mg twice daily. The minimum recommended interval between dose increases is 1 wk.


PO Start with 7 mg daily. Increase the dose in 7 mg increments to a maximum of 28 mg daily. The minimum recommended interval between dose increases is 1 wk.

Conversion from immediate release to ER

PO Patients taking immediate-release 10 mg twice daily may switch to ER 28 mg once daily the day following the last dose of an immediate-release 10 mg tablet.

Renal Function Impairment
Adults Immediate Release Severe renal impairment (CrCl 5 to 29 mL/min)

PO A target dosage of 5 mg twice daily is recommended. Patients taking 5 mg twice daily may switch to ER 14 mg once daily the day following the last dose of an immediate-release 5 mg tablet.

Mild to moderate renal impairment (CrCl 30 to 79 mL/min)

PO No dosage adjustment is recommended.

ER Severe renal impairment (CrCl 5 to 29 mL/min)

PO A target dosage of 14 mg/day is recommended.

Mild to moderate renal impairment (CrCl 30 to 79 mL/min)

PO No dosage adjustment is recommended.

General Advice

  • Administer without regard to meals.
  • ER capsules can be taken intact or may be opened, sprinkled on applesauce, and then swallowed. The entire contents of each capsule should be consumed; the dose should not be divided. Swallow capsules whole. The capsules should not be divided, chewed, or crushed.
  • Refer to the patient information for instructions on how to use the oral solution dosing device.


Store between 59° and 86°F.

Drug Interactions

Drugs eliminated via renal mechanisms (eg, cimetidine, hydrochlorothiazide, nicotine, quinidine, ranitidine, triamterene)

Plasma concentrations of both drugs may be altered. Use with caution. Monitor the clinical response of the patient and adjust treatment as needed.

Other NMDA antagonists (eg, amantadine, dextromethorphan, ketamine)

Has not been studied; use with caution.

Urinary alkalinizers (eg, carbonic anhydrase inhibitors, sodium bicarbonate)

Renal Cl of memantine is reduced approximately 80% under alkaline urine conditions at pH 8. Use with caution. Monitor the clinical response of the patient. Adjust the memantine dose as needed.

Adverse Reactions


Hypertension (4%); hypotension (2%); cardiac failure, cerebrovascular accident, syncope, transient ischemic attack (at least 1%); bradycardia; MI; atrial fibrillation, AV block (including second- and third-degree block), cardiac failure, cerebral infarction, deep venous thrombosis, ECG QT prolonged, INR increased, orthostatic hypotension, pulmonary embolism, QT prolonged, supraventricular tachycardia, tachycardia, thrombophlebitis, torsades de pointes (postmarketing).


Dizziness (7%); confusion, headache (6%); anxiety (4%); depression, hallucination, somnolence (3%); aggression, fatigue (2%); aggressive reaction, ataxia, hypokinesia, vertigo (at least 1%); agitation; convulsion; delirium; delusion; dementia of the Alzheimer type; insomnia; restlessness; tremor; claudication, depressed level of consciousness (including rare reports of coma), dyskinesia, encephalopathy, extrapyramidal disorder, hypertonia, intracranial hemorrhage, lethargy, loss of consciousness, malaise, NMS, parkinsonism, suicidal ideation, tardive dyskinesia (postmarketing).


Rash (at least 1%); Stevens-Johnson syndrome (postmarketing).


Cataract, conjunctivitis (at least 1%).


Constipation, diarrhea (5%); vomiting (3%); abdominal pain (2%); fecal incontinence; nausea; colitis, dysphagia, gastritis, gastroesophageal reflux, ileus, pancreatitis (postmarketing).


Urinary incontinence (2%); frequent micturition (at least 1%); UTI; acute renal failure (including abnormal renal function test), impotence, urinary retention (postmarketing).


Cholelithiasis, hepatic failure, hepatitis (including abnormal hepatic function test, cytolytic and cholestatic hepatitis) (postmarketing).


Anemia (at least 1%); agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombotic thrombocytopenic purpura (postmarketing).


Decreased weight, increased alkaline phosphatase (at least 1%); anorexia; decreased appetite; dehydration; hyperglycemia; peripheral edema; hyperlipidemia, hypoglycemia, hyponatremia (postmarketing).


Back pain (3%); arthralgia; pain in extremity; bone fracture, carpal tunnel syndrome, myoclonus (postmarketing).


Coughing (4%); dyspnea (2%); pneumonia (at least 1%); bronchitis; nasopharyngitis; upper respiratory tract infection; aspiration pneumonia (postmarketing).


Influenza (4%); pain, weight increased (3%); fall; gait disturbance; pyrexia; chest pain, sepsis, SIADH, sudden death (postmarketing).



Category B .




Safety and efficacy not established.

Renal Function

Dosage reduction recommended in patients with severe renal impairment.

Hepatic Function

Use with caution in patients with severe hepatic impairment.

GU conditions

Conditions that raise urine pH may decrease urinary elimination of memantine, resulting in increased plasma levels.


Has not been studied in patients with seizure disorders.



Agitation, asthenia, bradycardia, coma, confusion, diplopia, dizziness, ECG changes, increased BP, lethargy, loss of consciousness, psychosis, restlessness, slowed movement, somnolence, stupor, unsteady gait, vertigo, visual hallucinations, vomiting, weakness.

Patient Information

  • Advise patient or caregiver that this drug does not alter the Alzheimer process and that the efficacy of the medication may decrease over time.
  • Advise patient or caregiver that medication is started at a low dose and gradually increased at intervals of at least 1 wk.
  • Advise patient or caregiver to take without regard to meals, but to take with food if GI upset occurs.
  • Advise patients or caregiver that the ER capsules should be swallowed whole. Alternatively, the capsules may be opened and sprinkled on applesauce and the entire contents consumed. Do not divide, chew, or crush capsules.
  • Ensure that the patient or caregiver using oral solution understands how to attach the green cap and plastic tube to new bottles of oral solution, withdraw prescribed dose using dosing syringe, and administer the dose.
  • Caution patient that memantine may cause drowsiness or dizziness, and to use caution while driving or performing other activities requiring mental alertness or coordination until tolerance is determined.

Copyright © 2009 Wolters Kluwer Health.