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Memantine-Induced Hepatitis with Cholestasis in a Very Elderly Patient

Nicola Ferrara, MD; Graziamaria Corbi, MD, PhD; Annalisa Capuano, MD; Amelia Filippelli, MD, PhD; and Francesco Rossi, MD
[+] Article and Author Information

From University of Molese, Campobasso 86100, Italy, and Second University of Naples, Naples 80138, Italy.


Potential Financial Conflicts of Interest: None disclosed.


Ann Intern Med. 2008;148(8):631-632. doi:10.7326/0003-4819-148-8-200804150-00023
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Letter to Editor:
Posted on April 29, 2008
Thomas Finucane
Johns Hopkins Bayview Medical Center
Conflict of Interest: None Declared

To the Editor:

Dr. Ferrara and colleagues report a case of hepatitis due to memantine. Their Clinical Observation begins with the observation that, "Memantine, recently approved in Europe and the U.S. for treating dementia, has been show to reduce clinical deterioration in moderate-to- severe Alzheimer disease and in vascular dementia." (1)

This is misleading on two counts, in my opinion. First, "Memantine has been marketed in Germany (as Akatinol Memantine®) since 1982 for the treatment of organic brain syndrome", according to an FDA briefing document from it's vendors in 2003, (2) and was approved in the US in 2002. This is hardly "recent". Second, whether it produces any meaningful clinical benefit to patients remains uncertain. The National Institute for Health and Clinical Excellence recommends that it only be used as part of a clinical trial (3).

Another way of looking at it would be to ask whether it is possible that a drug that benefits patients with Alzheimer disease could be marketed in Germany for 20 years and somehow remain unnoticed and unused in the United States?

Reference List

(1) Nicola Ferrara, Graziamaria Corbi, Annalisa Capuano, Amelia Filippelli, and Francesco Rossi. Memantine-Induced Hepatitis with Cholestasis in a Very Elderly Patient. Ann Intern Med 2008; 148: 631-632

(2) Memantine HCI. Briefing document. (September 24, 2003). http://www.fda.gov/OHRMS/DOCKETS/ac/03/briefing/3979B1_01_ForestLabsMemantine.pdf accessed 04/28/2008.

(3) Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer's disease (amended). (September 2007). http://www.nice.org.uk/nicemedia/pdf/TA111QRGSept07.pdf accessed 04/28/2008.

Conflict of Interest:

None declared

The effect of hepatitis virus on memantine-induced hepatotoxicity
Posted on May 7, 2008
Liu Hong
Institute of Digestive Disease, Xijing Hospital, Fourth Military Medical University, Xi¡¯an, China
Conflict of Interest: None Declared

To the editor:

We read with interest the article by Ferrara N and colleagues (1). They have described the first case of memantine-induced hepatotoxicity in a very elderly patient with mixed, moderate dementia and behavior disorders. As the authors suggest, memantine may cause phospholipidosis in macrophages, which induce cell vacuolization and hepatocyte injury. In our opinions, other factors may contribute to the mechanism by which memantine causes cholestasis liver injury. Clinicians will need to know the results of liver biopsy. In China, memantine have caused severe but reversible hepatotoxicity in a 67-year-old man, who is a hepatitis B virus carrier. The patient presented with anorexia, jaundice, pale-colored stool, dark urine, itching, pedal edema and diarrhea. A liver biopsy showed marked portal edema, marked bile ductular proliferation and bile duct epithelial damage. However, the signs and symptoms didn't completely disappear untile memantine therapy was withdrawn and artificial liver therapy was performed for two times. It seens that hepatitis B virus may enhance the effect of memantine on hepatotoxicity. Could the authors comment on the factors, which enhance (or weaken) memantine-induced hepatotoxicity?

References:

1 Ferrara N, Corbi G, Capuano A, Filippelli A, Rossi F. Memantine- induced hepatitis with cholestasis in a very elderly patient. Ann Intern Med. 2008 Apr 15;148(8):631-2.

Conflict of Interest:

None declared

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