FDA downgrades the antiviral efavirenz to pregnancy category D.(Obstetrics)

The Food and Drug Administration has downgraded efavirenz to pregnancy category D, "Positive Evidence of Fetal Risk," and is urging women to avoid becoming pregnant while taking the antiretroviral drug.

The new package label stems from four retrospective reports of women who gave birth to infants with neural tube defects after first-trimester exposure to efavirenz (Sustiva). Three infants were diagnosed with meningomyelocele and one with Dandy Walker syndrome.

Physicians are being asked to report pregnant patients who have been exposed to efavirenz to the Antiretroviral Pregnancy Registry (800-258-4263), which was established to monitor fetal outcomes. The drug had previously been labeled category C: "Risk of Fetal Harm Cannot Be Ruled Out."

Bristol-Myers Squibb Co., Princeton, N.J., alerted health care providers to the label change in a letter dated March 2005 and made public in June. Signed by Freda C. Lewis-Hall, M.D., senior vice president for medical affairs, the letter urged pregnancy testing before women start on efavirenz.

"Though there are no adequate, well-controlled studies in pregnant women, Sustiva should be used during the first trimester of pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options," Dr. Lewis-Hall advised. "Barrier contraception should always be used in combination with other contraceptive methods."

Dr. Lewis-Hall described a prospective review of pregnancy outcomes for 206 women who carried 207 fetuses, while exposed to efavirenz. Five of 188 infants born after first-trimester exposure had birth defects; none were observed in 13 live births after second- or third-trimester exposures. Dr. Lewis-Hall did not describe the birth defects, except to say they were not neural tube defects, ...