The acne drug Accutane is as dangerous a cause of birth defects as thalidomide, causing 40% of women to miscarry and 25% to have children with severe birth defects if taken early in pregnancy, a study reported Thursday.
Thalidomide, a sedative, caused an epidemic of birth defects in Europe in the late 1950s and early ‘60s before it was withdrawn from the market.
Since Accutane was approved in the United States in late 1982, it has been linked to cases of miscarriage or birth defects in 25 states, said the author of the new study, Dr. Edward Lammer of the California Birth Defects Monitoring Program.
In a presentation in New Orleans at the annual meeting of the American Society of Human Genetics, Lammer reported that miscarriages occurred in 12 of 30 women studied, or 40%. Major birth defects occurred in 12 of 48 women studied, or 25%, he said.
“These unusually high risks are comparable to those posed by the thalidomide exposure,” Lammer said.
Neil Holtzman, a pediatrician and geneticist at Johns Hopkins University in Baltimore, said, “I don’t think there’s any doubt that it’s a real danger.” He agreed that the risks associated with thalidomide and Accutane--also called isotretinoin--are comparable.
Dr. Muin Khoury, a birth defects specialist at the U.S. Centers for Disease Control, said that about 25% of women who used thalidomide during pregnancy had children with birth defects, making its risk comparable to that reported for Accutane.
Accutane, made by Hoffmann-La Roche of Nutley, N.J., is now marketed with strong warnings about the risk of birth defects, and women of child-bearing age must sign a consent form before it can be prescribed to them, said Paula Frakes, spokeswoman for Hoffmann-La Roche.
“I’m not sure the way the drug is prescribed now is sufficiently protective,” Holtzman said.
Lammer said that in some European countries distribution of the drug is sharply restricted. A proposal to restrict its distribution here was not adopted by the U.S. Food and Drug Administration, Lammer said.
Frakes noted that additional requirements have been placed on doctors and patients when the drug is to be used in women of child-bearing age. The women must have a pregnancy test before taking the drug, for example, and must agree to use contraceptives, Frakes said. The company has offered to pay for the pregnancy test and for counseling on contraceptive use.
“We want to do everything in our power to make sure the drug is never taken during pregnancy,” she said in a telephone interview.
Lammer said that the birth defects associated with Accutane include abnormalities of the brain, the skull and face, the heart and the thymus gland, which governs the immune system.
An important difference between Accutane and thalidomide is that Accutane was known to be a cause of birth defects before it was approved; thalidomide was not. Furthermore, thalidomide was meant to be prescribed during pregnancy; Accutane is not. (Thalidomide, used as a tranquilizer and to control nausea, was never approved in the United States.)
In a separate report earlier in the meeting, Lammer said that another drug related to Accutane, called Tegison, also appears to cause birth defects.
Tegison, or etretinate, also made by Hoffmann-La Roche, additionally has the unfortunate ability to remain in the body for as long as two years after women stop taking it, Lammer reported.
“It poses a risk of birth defects even for people who stop using it before they conceive,” he said. The drug is used to treat psoriasis.
Both Accutane and Tegison are derivatives of Vitamin A. Lammer said there is some concern that Vitamin A itself might cause birth defects.
That is especially troubling because many multiple vitamin supplements intended to betaken during pregnancy contain Vitamin A, Lammer said. He said there is little evidence that Vitamin A has any benefits for pregnant women.