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Hepatitis Associated with Low-Dose Venlafaxine for Postmenopausal Vasomotor Symptoms

Clinical Pharmacy Specialist, Ambulatory Care, University of Iowa Hospitals and Clinics; and Assistant Professor (clinical), Division of Clinical and Administrative Pharmacy, University of Iowa College of Pharmacy, Iowa City, IA

Rachel R Digmann, PharmD

at time of writing, Specialized Resident in Primary Care, University of Iowa Hospitals and Clinics; now, Clinical Pharmacy Specialist, Kaiser Permanente, Denver, CO

M Gwen Beck, MD

Associate Professor, Department of Internal Medicine, College of Medicine, University of Iowa, and University of Iowa Hospitals and Clinics

Reprints: Dr. Phillips, Department of Pharmaceutical Care, University of Iowa Hospitals and Clinics, 200 Hawkins Dr., Iowa City, IA 52242-1009, fax 319/353-8443, beth-phillips{at}uiowa.edu

OBJECTIVE: To report a case of drug-induced hepatitis associated with low-dose venlafaxine.

CASE SUMMARY: A 60-year-old white woman receiving venlafaxine 75 mg daily for vasomotor symptoms presented after one month of therapy with nonspecific complaints, including abdominal pain. A series of diagnostic and laboratory tests revealed an enlarged liver and elevated alanine aminotransferase (ALT) up to 372 U/L, aspartate aminotransferase (AST) up to 99 U/L, -glutamyltransferase (GGT) up to 962 U/L, and alkaline phosphatase up to 758 U/L. All potential hepatotoxic medications were discontinued. Within one week after stopping venlafaxine, her liver function test results showed marked improvement. Almost 4 weeks after discontinuing therapy, venlafaxine 37.5 mg was reinitiated. Her ALT, AST, GGT, and alkaline phosphatase again increased to 269, 49, 256, and 263 U/L, respectively, 6 days after resuming therapy. Upon discontinuation of venlafaxine, her liver function abnormalities resolved.

DISCUSSION: This case is significant due to the severity of symptoms and consequent liver function test results involved in diagnosing drug-induced hepatitis. It is also remarkable because of the hepatotoxicity that occurred initially and on rechallenge with low-dose venlafaxine. The hepatotoxic effects of venlafaxine have been characterized as rare and idiosyncratic. The Naranjo probability scale revealed that the adverse drug event was probable.

CONCLUSIONS: Venlafaxine therapy can lead to drug-induced hepatitis, even when used at low doses. Clinicians should be aware of this possible adverse effect of venlafaxine therapy and monitor patients closely after initiation of therapy.

Key Words: hepatic transaminases, hepatotoxicity, venlafaxine

Published Online, January 17, 2006. www.theannals.com, DOI 10.1345/aph.1G339

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