Continued Occurrence of Accutane®-Exposed Pregnancies

Abstract

Accutane (isotretinoin, Roche Laboratories, Nutley, NJ) is a prescription drug approved by the US Food and Drug Administration to treat severe, treatment-resistant nodular acne that may cause major birth defects when the fetus is exposed in the first trimester of pregnancy. It is contraindicated in pregnancy, and the package carries an explicit warning. Despite the manufacturer instituting a Pregnancy Prevention Program (PPP) in 1988, exposed pregnancies continued to occur. In 1996 the manufacturer began a direct-to-consumer advertising campaign. The investigators examined recent trends in the use of Accutane by women of reproductive age (15-44 years). Data were taken from IMS HEALTH National Prescription Audit Plus and the National Disease and Therapeutic Index. In addition, 14 women with recent exposed pregnancies were interviewed to identify possible ways of preventing exposure. Between 1980 and 1999 the estimated annual number of Accutane prescriptions more than doubled to more than 1,800,000. The number written for women remains fairly stable at about 50%. Women of reproductive age consistently account for about 90% of all prescriptions for women. Assuming that the average prescription was for 30 days and that the average patient used Accutane for 5 months, an estimated 150,000 reproductive-aged women in the United States (2.5 per 1000) used the drug in 1999. Interviews revealed that most of the 14 exposed pregnancies were not contraceptive failures but rather failures to use contraception. Eight women acknowledged having intercourse at least once without using any form of contraception at the time of the exposed pregnancy. Ten women had a pregnancy test before starting to use Accutane, but three of them were in fact pregnant at this time despite a negative test (two urine tests and one blood test). Ten women were prescribed Accutane by a dermatologist, but two of them had used leftover medication from an earlier prescription. Half the women reported seeing an advertisement for prescription acne treatment before taking Accutane. All 14 women knew that the drug should not be used while pregnant, but none had seen all components of the PPP, and four did not see any components other than what is on the pill packet. One infant was born with major malformations consistent with Accutane embryopathy, while four others seemed well. There were four spontaneous and five induced abortions. Reproductive-age women are using Accutane to treat severe acne at an increasing rate. It is the most widely used teratogenic medication in the United States. When the drug is necessary, the physician should provide precautions and all elements of the PPP, and all recommended contraceptive measures should be followed. No woman of childbearing age who is not under care by a physician familiar with Accutane should use this medication.