Isotretinoin-related birth defects

Isotretinoin (also known as Accutane) is a drug used to treat severe acne, but it can cause birth defects when taken by pregnant women. Because of these risks, the U.S. Food and Drug Administration and Roche Pharmaceuticals (Accutane's manufacturer) developed a voluntary pregnancy prevention program (PPP) in 1988 to try and prevent conception in women taking the drug. This program was replaced in the U.S. in 2002 with the System to Manage Accutane Related Teratogenicity (SMART), a program that placed more emphasis on pregnancy testing and contraception.

A study published online October 14, 2005 in Birth Defects Research (Part A): Clinical and Molecular Teratology (www.interscience.wiley.com/journal/bdr) surveyed pregnant women who contacted a birth defect information service seeking information on the effects of isotretinoin. The purpose of the survey was to determine how the drug was dispensed in women who subsequently became pregnant and to identify possible reasons for failure in preventing conception.

Led by Julia Robertson of the Birth Defects and Genetics Program at the Utah Department of Health in Salt Lake City, researchers surveyed 34 women who had called a member service of the Organization of Teratology Information Services (OTIS) between April 2002 and September 2004 because they had become pregnant while taking isotretinoin. "The results of the OTIS survey show that the majority of women who participated were treated for less severe disease than is recommended in the SMART program," the researchers state. A total of 24 percent of the women reported receiving contraception counseling while taking the drug. In addition, the results showed that healthcare professionals and their patients failed to comply with a number of key SMART and/or PPP requirements. According to these requirements, women must have two negative pregnancy tests before receiving a prescription, yet 76 percent of the women in the study said they did not have a second pregnancy test during menstruation. When asked about the SMART requirement of receiving a pregnancy test each month before refilling a prescription, 35 percent of the women surveyed said they did not have monthly pregnancy tests during the therapy. SMART also requires women to use two forms of birth control simultaneously while taking isotretinoin, yet only 62 percent of the women reported using birth control and only 29 percent of these women reported using two forms of contraception. In addition, only 53 percent of the women reported signing the informed consent required by SMART prior to taking the drug.

The authors point out that the study's strengths include using counselors with extensive experience in communicating with women about their reproductive concerns and the fact that most initial interviews were completed within 3 months of exposure, before fetal outcome was known. They acknowledge that the study's limitations include the small number of women surveyed and the fact that responses are based on patient self-reporting and may be subject to recall error. "Nonetheless, women were surveyed prior to the outcome of the pregnancy, so we believe the responses provided in this report can be useful in elucidating important factors that hinder the success of pregnancy prevention programs," the authors state.

Last year, the FDA began examining ways of designing a new pregnancy program with stricter requirements to prevent isotretinoin-related birth defects and in August 2005 the new plan, called iPLEDGE, was announced. Beginning December 31, 2005, the regulations will require doctors and patients to register in an electronic database before the drug can be dispensed. The plan also includes the two pregnancy tests, two birth control methods, and other safeguards previously recommended by SMART.