In the news ... 2007

FDA issues Dear Doctor letter for Viracept

September 10, 2007

The Food and Drug Administration (FDA) has issued a Dear Doctor letter regarding a possible cancer-causing compound in the protease inhibitor Viracept (nelfinavir). The letter recommends that pregnant women who are taking Viracept switch to an alternative regimen, if one is available. The letter also recommends that children not begin a new regimen with Viracept . Other than pregnant women, anyone currently taking Viracept with undetectable HIV levels and who are clinically stable are not encouraged to switch.

The Dear Doctor letter follows up on an earlier recall of Viracept outside the US. In most of the world, Roche manufactures and sells Viracept. As reported in Manufacturer Recalls Viracept, Roche recalled all Viracept when ‘chemical impurities’ were detected. At that time, Pfizer (who manufactures and sells the drug in the US) issued a press release stating that their manufacturing facilities are completely separate from Roche’s, and there was no need to recall its product.

The chemical impurity is called ethyl methane sulfonate (EMS). It’s a byproduct of the manufacturing of Viracept. The FDA and Pfizer have agreed to test all of its batches of Viracept sold in the US, and only release those with EMS levels considered acceptable by the FDA.

EMS disrupts normal DNA function and can lead to cancers and birth defects at high enough levels. The EMS levels that the FDA considers safe are said to be ‘substantially lower’ than those found in the recalled, Roche-manufactured batches of Viracept. While the EMS levels in Pfizer’s version of the drug are believed to be lower than those in Roche’s, the exact amount in Pfizer’s drug is unclear. Moreover, a clear standard for acceptable levels has not yet been determined.

While it was once a popular treatment option, the use of Viracept has dropped off substantially in the US due to concerns about its lack of potency and high incidence of diarrhea. One area where it is still widely used is by pregnant women, where it has been considered safe.

The FDA uses a letter-rating scheme to categorize the risk of any drug to a developing fetus. The categories range from A (known to be safe) to X (known to be very dangerous, not to be used by women who are pregnant or may become pregnant). There are no anti-HIV drugs that are Category A. The protease inhibitors Reyataz (atazanavir), Prezista (darunavir), Invirase (saquinavir) and Norvir (ritonavir) are labeled Category B, which is defined as “Either animal reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).”

For more information on treating HIV during pregnancy, read the Federal Perinatal HIV Treatment Guidelines.