Serious Adverse Events Attributed to Nevirapine Regimens for Postexposure Prophylaxis After HV Exposures - Worldwide, 1997 - 2000 [MMWR 2001;49:1153]: The CDC reports two cases of life-threatening hepatotoxicity in healthcare workers given nevirapine for post-exposure prophylaxis. One was a 43-year-old female who required a liver transplant, and the second was a 38-year-old male physician who was hospitalized with life-threatening fulminant hepatitis. Both healthcare workers were taking nevirapine, AZT, and 3TC. A review of MedWatch showed 12 cases of hepatotoxicity as the cause of serious reactions to nevirapine taken for PEP during the period March 1997 to September 2000. The median time to the first abnormal liver test was 21 days. Eleven patients reported symptoms including fever, malaise, and abdominal pain; the median time for onset of symptoms was 14 days after beginning nevirapine. There were also 14 cases of skin rash with one documented and two possible cases of Stevens-Johnson syndrome; the median time for onset of rash was nine days. The authors conclude that persons taking nevirapine for PEP are at risk for serious adverse reactions.
Comment: Nevirapine is not currently recommended in the CDC guidelines for PEP [MMWR 1998;47:RR-1]. Nevertheless, this has been a potentially attractive agent based on the data showing prevention of perinatal transmission and the theoretical advantage of rapid activity since nevirapine does not require phosphorylation for activation. A possible confounding feature here is that most of the healthcare workers were taking 200 mg twice daily for the one-month prophylaxis, although the standard dose for HIV treatment is 200 mg once daily for two weeks as the "lead in" prior to 200 mg twice daily. The authors from the CDC point out that nevirapine has never been advocated by the CDC for PEP, and also notes that these observations should not deter application of their current recommendations for nevirapine to prevent perinatal transmission, since no serious toxicity has been reported among mother-infant pairs using the standard regimen for this setting.
Viramune Expands Hepatotoxicity Warning ["Dear Health Care Professional" issued 11/9/00 from Dr. Manfred Haehl, Senior Vice President for Roxane]: The supplier of nevirapine (Viramune) has warned health care professionals about increasing reports of hepatotoxicity as well as cutaneous reactions as potentially fatal side effects. The letter notes that two-thirds of the serious cases of hepatotoxicity occurred in the first 12 weeks of therapy, so that this is the "critical period during which intensive clinical and laboratory monitoring, including liver function test, is essential." The frequency of monitoring is unclear, but "some experts" recommend measuring AST or ALT at baseline, with the dose escalation at two weeks, then at monthly intervals for the first 12 weeks, and then intermittently there after. The risk of hepatotoxicity is increased with chronic hepatitis due to HBV or HCV. The use of prednisone to prevent the nevirapine-associated rash, once a popular ploy, is no longer recommended. Patients should be warned of both the potential for hepatitis and for serious skin reactions.
posted 1/18/2001

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