The Food and Drug Administration has announced changes that strengthen a risk management program regarding pregnancy and a drug used to treat severe acne. Accutane (isotretinoin) is a drug approved to treat the most serious form of acne--a type that is painful, permanently disfiguring, and does not respond to other acne treatments. Accutane is very effective, but its use carries significant potential risks, including birth defects and even fetal death.

The new risk management program is called S.M.A.R.T., the System to Manage Accutane-Related Teratogenicity. "Teratogen" refers to any substance with the potential to cause birth defects. S.M.A.R.T. was developed in consultation with the FDA by Accutane's manufacturer, Roche Laboratories of Nutley, N.J. The program is designed to enhance safe and appropriate use of the drug by strengthening an existing patient education program known as the Accutane Pregnancy Prevention Program.

In recent years, as more and more women have been receiving Accutane prescriptions, the risk that pregnant women may be inappropriately using the drug has increased. In September 2000, the FDA held a meeting of its dermatologic and ophthalmic drugs advisory committee to discuss what additional measures might help prevent exposure of unborn babies to Accutane.

The S.M.A.R.T. program was developed to address the two main goals identified at the meeting. The first is that no woman should begin Accutane therapy if she is pregnant; and second, no pregnancies should occur while a woman is taking Accutane.

The risk management components are described fully within the boxed contraindications and warnings (Black Box) and the precautions sections of the Accutane package insert, which provides prescribing information for health-care professionals. The S.M.A.R.T. program requires the following:

• Doctors who prescribe Accutane must study the S.M.A.R.T. "Guide to Best Practices" provided by Roche, and then sign and return to Roche a "Letter of Understanding" certifying their knowledge of the measures to minimize fetal exposures to Accutane. The manufacturer has also developed a continuing medical education (CME) course for Accutane prescribers that includes specific, practical information about pregnancy prevention. The FDA strongly encourages participation in this half-day course. Accutane prescribers will then receive special self-adhesive Accutane qualification stickers from Roche. All Accutane prescriptions should have the special yellow sticker attached to the prescriber's regular prescription form. This sticker will indicate to the pharmacist that the patient is "qualified" according to the new package insert. This means the patient has had negative pregnancy tests as described below, as well as education and counseling about pregnancy prevention. The pregnancy test will be repeated every month throughout the Accutane treatment course, and no prescriptions should be given for more than a one-month supply of Accutane at a time.
• All female patients must have two negative urine or serum pregnancy tests before the initial Accutane prescription is written. And for each month of therapy, they must have a negative pregnancy test result before receiving their next prescription, regardless of whether they are sexually active. Patients who are, or who might become, sexually active with a male partner must also select and use two forms of effective contraception simultaneously for at least one month before initiation of Accutane therapy, during therapy, and for one month following discontinuation of therapy, according to the program. They must sign a patient information/consent form about Accutane and birth defects, in addition to the consent form that all patients should receive about other potentially serious risks related to Accutane. Finally, female patients must be given the opportunity to enroll in the Accutane survey. This confidential survey will collect data to help Roche and the FDA decide if S.M.A.R.T. is helping to prevent exposure of unborn babies to Accutane.
• Pharmacists will dispense Accutane only upon presentation of a prescription with the special Accutane qualification sticker. Pharmacists will dispense a maximum one-month supply of Accutane, fill prescriptions within seven days from the date of "qualification" and provide a medication guide for patients with each Accutane prescription. Requests for refills and phoned-in prescriptions will not be filled.

Exposure of an unborn baby to Accutane is a serious adverse event and should be reported to Roche Medical Services at 1-800-526-6367 or the FDA MedWatch program at 1-800-FDA-1088 (1-800-332-1088). MedWatch can also be accessed via the Internet at www.fda.gov/medwatch/.