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.
|Medication:||Memantine (10 mg daily)|
|Severity:||2+ (jaundice, no mention of hospitalization)|
|Recovery:||Within 20 days|
|Other medications:||Digoxin, lisinopril, tiapride, alprazolam and promazine|
|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|
|DRUG||CAS REGISTRY NUMBER||MOLECULAR FORMULA||STRUCTURE|
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