FDA Warns Antiretroviral Drug Viramune Can Cause Liver Damage; Says Drug Still Important Option for HIV-Positive PeopleFDA on Wednesday said it recently revised the side-effect warnings for Boehringer Ingelheim's antiretroviral drug Viramune -- which is known generically as nevirapine -- to say that the drug can cause "deadly liver damage," Reuters reports. However, the agency said that nevirapine remains a "key option" for many HIV-positive people, Reuters reports (Richwine, Reuters, 1/20). "Both clinically symptomatic and asymptomatic liver toxicity are observed with long-term use of nevirapine in combination with other HIV drugs," FDA said in a release, adding, "Symptomatic nevirapine toxicity consists of elevated liver enzymes plus at least one symptom, which is typically [a] rash but may include flu-like symptoms or fever. The severity of symptomatic liver toxicity ranges from mild symptoms ... to rapidly occurring liver failure and death" (FDA release, 1/19). However, no "serious" liver toxicity or deaths have been reported when a single dose of the drug has been given to an HIV-positive pregnant woman to prevent mother-to-child HIV transmission, according to Reuters. "In spite of the potential for serious and life-threatening liver toxicity and skin rashes with nevirapine, there are multiple reasons why nevirapine remains an important part of an HIV treatment regimen (for many people)," FDA said.
Controversy Over Nevirapine
South Africa's ruling African National Congress has recently accused U.S. officials of conspiring with Boehringer Ingelheim to hide the drug's side effects, which U.S. officials dispute, Reuters reports (Reuters, 1/20). The charge came after a recent series of Associated Press articles criticized the conduct of a trial of nevirapine among pregnant women in Uganda. The articles concerned an NIH-funded trial that began in 1997 to study the use of nevirapine in single doses among HIV-positive pregnant women in Uganda to determine the drug's ability to prevent vertical HIV transmission. The initial results showed that the drug prevented HIV transmission to newborns in as many as half of births. By early 2002, medical safety specialists and auditors with NIH as well as Boehringer Ingelheim all cited "widespread" problems with the research in Uganda -- including a failure to receive participants' consent about changes in the study, administration of incorrect doses, and delays in reporting and underreporting of fatal and life-threatening reactions to the drug. Because of the reported problems, NIH suspended the research from spring 2002 to summer 2003 in order to review the trial and take corrective steps. Last month, National Institute of Allergy and Infectious Diseases Division of AIDS Director Dr. Edmund Tramont also admitted to rewriting a safety report on the use of nevirapine in pregnant women in order to change its conclusions and remove negative information about the drug. However, NIAID in a recent Q & A document regarding the trial said that nevirapine is a "safe and effective" treatment to reduce the risk of vertical HIV transmission and that reviews of the study data "have found only a very small number of serious adverse reactions that potentially might be due to nevirapine." NIH in July 2004 asked the Institute of Medicine to conduct a review of the Ugandan trial, and its results are expected in March. Some South African HIV/AIDS experts said the articles are threatening to undermine the drug's use to prevent infection among newborn infants in developing countries (Kaiser Daily HIV/AIDS Report, 1/7).