February 2001
ATLANTA
- Two health care workers who took nevirapine for post-exposure prophylaxis
following HIV exposure developed life-threatening hepatotoxicity, according to
the Centers for Disease Control and Prevention (CDC).
In addition, 22 case reports of adverse events associated with nevirapine (Viramune, Roxane) for post-exposure prophylaxis were reported from March 1997 to September 2000. Nevirapine is not currently recommended for post-exposure prophylaxis. Its initial success for prevention of perinatal HIV transmission may have sparked interest in its use in the occupational exposure setting.
According to the Morbidity and Mortality Weekly Report a 43-year-old female health care worker needed a liver transplant after developing fulminant hepatitis and end-stage hepatic failure after taking nevirapine, zidovudine (AZT, Retrovir, GlaxoSmithKline) and lamivudine (3TC, Epivir, GlaxoSmithKline) following an accidental needlestick. Similarly, a 38-year-old male doctor was hospitalized with life-threatening fulminant hepatitis while taking the above drug combination after mucous membrane exposure.
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Other reported adverse events included hepatotoxicity (12 of 22), skin reaction (14 of 22) and rhabdomyolysis (1 of 22). Four cases had both hepatotoxicity and skin reaction and one had rhabdomyolysis and skin reaction. More than half of the reported cases occurred inside the United States.
Of the 12 patients with hepatotoxic reactions, one developed liver failure (the patient requiring transplantation), seven had clinical hepatitis (jaundice, fever, nausea, vomiting, abdominal pain and/or hepatomegaly) and four had elevations in serum liver enzymes (alanine aminotransferase and aspartate aminotransferase) without reports of clinical hepatitis.
Numerous reports of health care workers (HCWs) who may have developed rashes or other milder illnesses after using nevirapine played into the current rationale for not recommending nevirapine for post-exposure prophylaxis for occupational exposure to HIV.
The two HCWs who developed life-threatening hepatotoxicity were taking AZT and 3TC along with nevirapine; but "the reason nevirapine was felt to be the causative agent is there were other reports of similar occurrences in HIV-infected persons taking it for treatment," said Elise Beltrami, MD, medical epidemiologist, CDC.
Symptoms disappeared for some patients on combination post-exposure prophylaxis when nevirapine was stopped, despite continuation of therapy with other drugs, said Beltrami.
"I think clinicians have always had a high degree of suspicion that it was nevirapine specifically [that caused adverse events]. We don't know for sure if any of these drugs are safe [as post-exposure prophylaxis]. They're used mainly in HIV-infected persons, but there's not good experience with them in non-infected or healthy persons who might take it for post-exposure prophylaxis."
The current indication for nevirapine calls for lead-in dosing, starting with a lower dose for the first two weeks then an increase in dosage. According to the CDC, nine of the 22 case patients took 200 mg of nevirapine daily, and 12 took 200 mg BID. (The dose for one case patient was not recorded.) At least six case reports of adverse events did not start with lead-in dosing.
"That may certainly have played a part in the serious adverse events. But I can say for sure that the patient who required the liver transplant was on the lower dose. We don't want to say the lower dose is safe because obviously some very significant adverse events have occurred in people who took the recommended lower dose," said Beltrami.
Current guidelines for post-exposure prophylaxis for occupational exposures call for two drugs, mainly AZT and 3TC. Two-drug therapy is considered the baseline regimen, and for higher risk exposures a third drug is recommended, usually a protease inhibitor like indinavir (Crixivan, Merck) or nelfinavir (Viracept, Agouron).
"I think the bottom line is that for post-exposure prophylaxis you really have to weigh the risks of exposure with the risks of taking the drugs. The risk of HIV transmission after an occupational exposure is very low. It's around 0.3%. You have to weigh that carefully against the risk of the drugs you might use for post-exposure prophylaxis."
For more information:
- CDC. Serious adverse events attributed to nevirapine regimens for post-exposure prophylaxis after HIV exposures - Worldwide, 1997-2000. MMWR. 2001;49(51/52):1153.
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