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Memantine is an oral N-methyl-D-aspartate glutamate receptor antagonist used in the therapy of Alzheimer disease and dementia.  Memantine is associated with a minimal rate of serum enzyme elevations during therapy and has only rarely been implicated as a cause of clinically apparent acute liver injury.



Memantine (mem' an teen) is an antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptors and has been shown to reduce the rate of clinical deterioration in moderate-to-severe Alzheimer disease.  The mechanism by which inhibition of NMDA receptors is beneficial in dementia is not known, but Alzheimer disease is characterized by persistent activation of these receptors and their antagonism may reduce excitotoxicity.  Memantine was approved for use in the United States in 2003 as therapy for moderate-to-severe dementia due to Alzheimer disease.  Memantine is available in tablets of 5 and 10 mg under the brand name Namenda.  It is also available as an oral solution (2 mg/mL).  The usual maintenance dose is 10 to 20 mg daily.  Side effects are not common but can include headache, dizziness, agitation, anxiety, fatigue, insomnia, diarrhea, nausea, vomiting, and rash.



In large placebo controlled trials, the rate of serum enzyme elevations during memantine therapy was similar to that in patients on placebo and no instances of clinically apparent liver injury were reported.  Nevertheless, since its introduction into clinical use, memantine has been implicated in at least one report of clinically apparent hepatotoxicity.  The time to onset was 3 weeks and the clinical syndrome was that of an acute cholestatic hepatitis which was mild-to-moderate in severity and rapidly reversible upon drug discontinuation.  Immunoallergic and autoimmune features were not present.


Mechanism of Injury

Memantine is minimally metabolized by the liver and excreted mainly in the urine.  The mechanism by which it might cause hepatotoxicity is not known.


Outcome and Management

Cases of hepatotoxicity from memantine have been too few to characterize clinically.  There have been no published reports of acute liver failure, chronic hepatitis or vanishing bile duct syndrome attributed to memantine.  There is no information on the possible cross sensitivity to liver injury of memantine with the acetylcholinesterase inhibitors or other NMDA antagonists such as amantadine.

References regarding the safety and potential hepatotoxicity of the drugs used for Alzheimer disease are provided together after the Overview section of Alzheimer Disease Agents.

Drug Class:  Alzheimer Disease Agents


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Case 1.  Mild acute cholestatic hepatitis due to memantine
[Modified from:  Ferrara N, Corbi G, Capuano A, Filippelli A, Rossi F. Memantine-induced hepatitis with cholestasis in a very elderly patient. Ann Intern Med 2008; 148: 631-2. PubMed Citation]


A 92 year old woman with dementia developed pruritus, dark urine and jaundice 16 days after starting memantine (5 mg daily for 8 days followed by 10 mg daily).  She had no history of liver disease, risk factors for viral hepatitis or alcohol use.  Her other medications included dignoxin, lisinopril, tiapride, alprazolam and promazine which she had taken chronically.  She had no history of drug allergies.  She had no fever or rash.  Liver tests showed serum bilirubin of 4.3 mg/dL (2.5 mg/dL direct), ALT 132 U/L, AST 74 U/L, alkaline phosphatase 912 U/L and GGT 155 U/L.  Serum immunoglobulins were normal and AMA was negative as were tests for hepatitis A, B and C.  Ultrasound of the abdomen showed no evidence of biliary obstruction.  Memantine was discontinued and laboratory results began to improve (Table).  Her other medications were continued.  All liver tests were normal 20 days after stopping memantine.


Key Points

Medication: Memantine (10 mg daily)
Pattern: Cholestatic (R=0.3)
Severity: 2+ (jaundice, no mention of hospitalization)
Latency: 16 days
Recovery: Within 20 days
Other medications: Digoxin, lisinopril, tiapride, alprazolam and promazine

Laboratory Values

Time After Starting Time After Stopping ALT (U/L) Alk P (U/L) Bilirubin (mg/dL) Other
0 Memantine started (5 mg/d for 8 days, then 10 mg/d)
16 days 1 day 132 912 4.3 Memantine stopped
20 days 5 days 71 189 13.3 Normal ultrasound
35 days 20 days 50 186 11.8
Normal Values <56 <126 <1.2


An elderly woman developed a mild cholestatic hepatitis within 2 to 3 weeks of starting memantine and recovered promptly with its discontinuation.  The major differential diagnosis is biliary obstruction from gallstones or malignancy which was effectively excluded on the basis of the normal ultrasound, absence of fever and abdomenal pain and full recovery on stopping the implicated medication.  Memantine is generally well tolerated and liver injury from its use is very rare.




Memantine – Namenda®


Alzheimer Disease Agents



Product labeling at DailyMed, National Library of Medicine, NIH


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Memantine 19982-08-2 C12-H21-N Memantine Chemical Structure

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  1. PubMed logoRecent References on Memantine

  2. Clinical Trials logoTrials on Memantine

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