Fatal Skin Reactions Reported for HIV Drug

By Elizabeth Mechcatie
Elsevier Global Medical News

Warnings about severe skin reactions associated with the antiretroviral drug etravirine are being strengthened to include reports of hypersensitivity reactions and fatal cases of toxic epidermolysis necrolysis associated with the drug, says a notice posted on the Food and Drug Administration's MedWatch site.

The notice states that there have been postmarketing reports of cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme, "as well as hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure."

Both the FDA notice and a health care professional letter from the manufacturer, Tibotec Therapeutics, recommend that patients with signs and symptoms of severe skin or hypersensitivity reactions should immediately stop taking the drug.

Etravirine, a non-nucleoside reverse transcriptase inhibitor marketed as Intelence, was approved in January 2008 for use in combination with other antiretrovirals for treating HIV-1 infection in treatment-experienced adults. Warnings in the label at that time included a statement about "severe and potentially life-threatening" skin reactions that had been reported in fewer than 0.1% of patients on etravirine, including Stevens-Johnson syndrome, hypersensitivity reactions, and erythema multiforme. In clinical trials, the rash in general was mild to moderate and occurred primarily during the second week of treatment and was "infrequent" after the fourth week of treatment. In phase III studies, the drop-out rate due to rash in treated patients was 2%, the original label said.

This section now says etravirine treatment should be stopped immediately "if signs or symptoms of severe skin reactions or hypersensitivity reactions develop," according to the letter. A delay in stopping treatment "may result in a life-threatening reaction."

Serious adverse events that may be associated with etravirine should be reported to the company at 877-732-2488, or the FDA's MedWatch adverse event reporting program at 800-332-1088 or http://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm. 

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