A “Dear Healthcare Provider” letter has been issued in the US advising that pregnant women should not start an anti-HIV regimen that contains nelfinavir (Viracept), or switch to an alternative regimen if they are already taking the drug. The letter also states that children aged under 16 years should not initiate treatment with nelfinavir.
The letter was issued by Pfizer, who manufacture and market nelfinavir in the US and Canada. In June this year, nelfinavir manufactured in Europe (and distributed to countries around the world) was recalled by Roche after it was discovered that some batches of the drug had been contaminated with excess amount of ethyl methanesulfonate (EMS), large quantities of which have been shown to cancer in rats.
Because of this recall, the US Food and Drug Administration requested that Pfizer introduce new guidance to limit patient exposure to EMS.
Tests on nelfinavir in the US found levels of EMS considerably lower than those that prompted the recall of nelfinavir in Europe.
Nevertheless the FDA and Pfizer have agreed interim and long-term EMS exposure levels. The interim level of EMS exposure would involve a theoretical increased lifetime cancer risk of less than 17 cases per 100,000 exposed individuals. The long-term specification for EMS exposure limits the theoretical lifetime increased risk of cancer to less than one case per 100,000 exposed patients.
“Pfizer is taking this step to balance the need to maintain the availability of Viracept as a therapeutic alternative for patients and prevent unexpected interruption of HIV-1 antiretroviral treatment with the need to minimize patient exposure to a potential carcinogen”, states the letter.
Special recommendations have been made to limit the exposure of children and pregnant women to EMS and nelfinavir.
It is thought that children aged between two and 16 years have a threefold increased risk of developing cancer after exposure to EMS, and that infants under this age have an even greater risk. Because of this, Pfizer and the FDA have recommended that, until further notice, children should not start anti-HIV therapy with nelfinavir.
However, for infants and children who are already taking a stable regimen that contains nelfinavir “the FDA and Pfizer agree that the benefit-risk ratio remains favourable and those children may continue to receive Viracept.”
Although there is no evidence that women who took nelfinavir during pregnancy had an increased risk of having a baby with birth defects, the FDA is nevertheless recommending that women should limit their exposure to EMS during pregnancy.
Therefore, pregnant women should not initiate antiretroviral therapy that contains nelfinavir, and pregnant women currently taking nelfinavir should switch to an alternative regimen. If a pregnant woman had no other treatment options available, then the FDA and Pfizer have agreed that benefits of continuing to take nelfinavir outweigh the potential risks.
There are no changes to the recommended use of nelfinavir in other patients, and the letter states, “in considering the best treatment for patients, please be aware that many HIV antiretroviral medications are carcinogenic in animal studies.”