A letter from the manufacturer concerning a possibly carcinogenic chemical found in the antiretroviral drug nelfinavir (Viracept), used to treat HIV-1 infection, has been issued to health care providers. Ethyl methanesulfonate (EMS), an impurity formed in the nelfinavir manufacturing process, has been found in animal studies to be teratogenic, mutagenic, and carcinogenic, and although there are no data pertaining to its effects on humans, it is suspected that they might be comparable. The association between antiretroviral medication and serious adverse effects in animals is not unique to nelfinavir--other antiretrovirals have been noted to be carcinogenic, teratogenic, or mutagenic in animal studies. What appear worrisome are the high levels of EMS found in nelfinavir marketed in Europe that prompted the manufacturer to recall the drug from all its markets in the European Union and other parts of the world in June 2007. Pfizer has analyzed its nelfinavir produced and marketed in the United States and found levels of EMS to be lower than those found in the product released in the European market. To prevent high levels of EMS in nelfinavir in the United States, Pfizer and the Food and Drug Administration (FDA) have agreed to "implement a new specification to limit" its presence in the product.

Because of the assumed higher lifetime risk associated with the exposure to a carcinogen among pediatric patients, Pfizer and the FDA are recommending that any drug regimen involving nelfinavir not be initiated in such patients until notice to the contrary is given. Children already receiving the drug should continue to receive it because the benefit conferred is expected to be greater than any possible risk posed. Treatment with nelfinavir should not be initiated in pregnant patients either, and those already taking the drug should change to another antiretroviral medication as a precaution. Despite the absence of any data from the Antiretroviral Pregnancy Exposure Registry indicating any higher risk posed to infants born to mothers who take nelfinavir, the FDA is recommending the limitation of exposure to EMS during pregnancy.

Pfizer Inc. Dear healthcare professional [letter]: Viracept (nelfinavir mesylate) 250 mg, 625 mg tablets, and powder for oral suspension. Important information for prescribers. Sep 10, 2007. http://www.fda.gov/medwatch/safety/2007/VIRACEPT_HCPLetter_9_10_07.pdf.