Background:

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, SEC conducted the Isotretinoin Survey under the sponsorship of the manufacturers of generic isotretinoin (SEC 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.

Objectives:

To determine the rate of pregnancy among women of childbearing age who use isotretinoin;

To assess physician and patient compliance with the pregnancy RMP.

Methods:

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.

Results:

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 SEC 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 SEC 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:

Allen A. Mitchell, M.D., Principal Investigator
Carla M. Van Bennekom, R.N., M.P.H., Co-Investigator

Source of funding:

Barr Laboratories
Bertek Pharmaceuticals
Ranbaxy Pharmaceuticals

Study Period:

December 2002 - March 2006

Program Publications:

Link to Publications

Presentations:

Link to Presentations