Survey of Isotretinoin Use in Women
Isotretinoin is a drug uniquely effective for the treatment of severe acne; however, it is also a potent human teratogen. Isotretinoin is marketed as Accutane by its innovator, Hoffmann-La Roche, and as Amnesteem, Claravis, and Sotret by three manufacturers of generic products. In 2002, to minimize the risk of pregnancy during isotretinoin treatment, the manufacturers, with guidance from FDA, instituted a mandatory, multi-component risk management program (RMP) directed at physicians and patients. To evaluate the effectiveness of this program, the Slone Epidemiology Center conducted the Isotretinoin Survey under the sponsorship of the manufacturers of generic isotretinoin (Slone also designed the Accutane Survey and conducted that survey from 1989-2003). The Survey concluded in 2006 when the manufacturers implemented a new RMP, which included mandatory registration of all patients.
- To determine the rate of pregnancy among women of childbearing age who use isotretinoin.
- To assess physician and patient compliance with the pregnancy RMP.
The Survey sought to enroll all females taking any form of isotretinoin. Enrollment was voluntary; women could enroll on forms obtained from their physicians or on forms provided in every medication package. Mailed questionnaires, sent during isotretinoin treatment and six months after discontinuing the drug, requested information about women’s understanding of the teratogenic risks of isotretinoin, their pregnancy prevention practices, and the occurrence of pregnancies.
The Survey enrolled 37,765 women; the Survey concluded before all women completed follow-up. Compliance with most areas of the RMP was high. Based on information from 19,476 women who completed follow-up, the pregnancy rate was 1.9 per 1,000 140-day courses of isotretinoin. Since all women who enrolled in the Slone Isotretinoin Survey took isotretinoin after the introduction of the new pregnancy RMP, it is important to note that this rate is consistent with the rate observed in the years of the Slone Accutane Survey immediately preceding the initiation of the new RMP (for the 2000-2002 enrollment cohorts in that survey, the pregnancy rate varied from 1.1 to 1.8 per 1,000 140-day courses).
Investigators and Study Staff
Allen A. Mitchell, M.D., Principal Investigator
Carla M. Van Bennekom, R.N., M.P.H., Co-Investigator
Sources of Funding:
- Barr Laboratories
- Bertek Pharmaceuticals
- Ranbaxy Pharmaceuticals
December 2002 to March 2006
- Van Bennekom CM, Mitchell AA. An evaluation of a sticker-based RMP for isotretinoin [abstract]. Pharmacoepidemiol Drug Safety 2006;15:S12.
- Van Bennekom CM, Cho YK, Mitchell AA. Risk factors for pregnancy among isotretinoin users [abstract]. Pharmacoepidemiol Drug Safety 2004;13:S270.
- Van Bennekom CM, Mitchell AA. The Accutane Survey: 14 Years’ experience [abstract]. Pharmacoepidemiol Drug Saf 2003;12:S130-1.
- Van Bennekom CM, Mitchell AA. An assessment of the Accutane (Isotretinoin) Pregnancy Prevention Program. Annual meeting of Drug Information Association, Denver, CO, July 2001.
- Van Bennekom CM, Mitchell AA. One country’s programs for preventing pregnancies in women exposed to teratogens: experiences with Accutane and thalidomide in the US . International Symposium on Prevention and Epidemiology of Congenital Malformations, Cardiff, UK, September 2000.
- Van Bennekom CM, Mitchell AA. S.T.E.P.S. and the Accutane pregnancy prevention program: monitoring drugs with recognized teratogenic potential. Annual meeting of Teratology Society, Keystone, CO, July 1999.
- Van Bennekom CM, Mitchell AA, Louik C. Experience with Accutane. University of Utah conference: Thalidomide: Impact on the practitioner, Salt Lake City, UT, January 1999.
- Rao RS, Glynn RJ, Werler MM, Van Bennekom CM, Mitchell AA. Comparison of alternative survey methods for sensitive self-reported behaviors [abstract]. Am J Epidemiol 1997;145:544.
- Van Bennekom CM, Mitchell AA, Louik C. Experience with efforts to prevent use of isotretinoin during pregnancy. Annual meeting of Teratology Society, Keystone, CO, June 1996.
- Mitchell AA, Louik C, Van Bennekom C. Can human teratogens be used with relative safety? A novel survey method. Annual meeting of American Epidemiological Society, Pittsburgh, PA, March, 1993.
- Mitchell AA, Louik C, Gute DM. Accutane exposure in pregnancy–a novel survey design [abstract]. Teratology 1990;41:578.
- Mitchell AA, Van Bennekom CM. Response to FDA letter on Accutane Survey [letter to the editor]. J Am Acad Dermatol 2003;49:1201-2.
- Rao RS, Glynn RJ, Werler MM, Van Bennekom CM, Mitchell AA. Comparison of alternative survey methods for sensitive self-reported behaviours in a follow-up study of isotretinoin. J Epidemiol Biostat 2000;5:133-6.
- Chambers CD, Jones KL, Lammer EJ, Van Bennekom CM, Mitchell AA. Accutane-exposed pregnancies–California, 1999. MMWR 2000;49:28-31.
- Mitchell AA, Van Bennekom C, Louik C. A pregnancy-prevention program in women of childbearing age receiving isotretinoin. N Engl J Med 1995;333:101-6.