FDA’s ‘New’ Program to Prevent Birth Defects Caused By Acne Drug Isotretinoin (ACCUTANE) Is Powerless

The Food and Drug Administration (FDA) announced a “new” program on November 1, 2001 to prevent pregnancies and eliminate fetal exposure in women taking the acne drug isotretinoin (ACCUTANE) produced by Roche Laboratories of Nutley, New Jersey. The stated goals of the program are that: 1) no woman should begin isotretinoin treatment if she is pregnant; and 2) no pregnancies should occur while a woman is on the drug.

Isotretinoin is approved to treat the most serious form of acne, known medically as severe recalcitrant nodular acne. This form of the disorder is painful, permanently disfiguring, and not responsive to other acne treatments. It is very effective for this condition, but its use carries significant potential risks, including birth defects and even fetal death. According to the FDA, the new program is designed to enhance the safe and appropriate use of isotret-inoin by strengthening Roche’s Pregnancy Prevention Program described as “a comprehensive patient education program.” By any accounting the program has been a tragic failure. The FDA estimates that between 1982, when isotretinoin was approved, and last June 30, there have been 2,181 reports of women becoming pregnant while using isotretinoin. This number includes 1,310 elective abortions, 242 spontaneous abortions, 192 normal babies born and 166 reports of babies born with birth defects. Remember, that only 1 in 10 serious adverse drug reactions are typically reported to the FDA.

The new program goes by the catchy acronym SMART (System to Manage Accutane Related Teratogenicity). Unfortunately for those who have been adversely affected since isotretinoin was approved in 1982, the FDA failed to adopt similar steps urged by Public Citizen’s Health Research Group, in petitions filed in 1983 and 1988. The major difference between our recommendations and the new program is FDA’s inadvisable reliance on the private sector (Roche in this case) to ensure the safe use of isotretinoin. It has become painfully obvious that relying on the private sector to protect public safety is folly. Roche’s dominant concern is profit from isotretinoin sales, not the safety of its users. Since true public control of SMART may very well decrease the corporate bottom line, the company would rather stay in control to minimize such damage.

An overview of the failure of the FDA to properly regulate isotretinoin over the years and our recommendations can be found in our September 18, 2000 comments before the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee meeting on isotretinoin. This document is available on our web site at www.citizen.org/publications/release.cfm?ID=6738 or by writing to the Health Research Group, 1600 20th Street, N.W., Washington, DC 20009.

The major elements of the SMART program are:

• Prescribers must study the SMART “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 isotretinoin. Roche has also developed a Continuing Medical Education (CME) course for prescribers that includes specific, practical information about pregnancy prevention. The FDA strongly encourages participation in this half-day course. Prescribers will then receive from Roche special self-adhesive Accutane Qualification Stickers. All prescriptions for isotretinoin should have the special yellow sticker attached to the prescribers’ regular prescription form. This sticker will indicate to the pharmacist that the patient is “qualified” according to the new package insert, which means that she 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 isotretinoin treatment course, and no prescriptions should be given for more than a one-month supply at a time.
• Female patients must have two negative urine or serum pregnancy tests before the initial isotretinoin 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 might become, sexually active with a male partner must also select and use two forms of effective contraception simultaneously for at least one month prior to initiation of isotretinoin therapy, during therapy, and for one month following discontinuation of therapy. They must sign a Patient Information/Consent form about isotretinoin and birth defects, in addition to the Consent Form that all patients should receive about other potentially serious risks. Finally, female patients must be given the opportunity to enroll in the Accutane Survey. This confidential survey will collect data to help decide if SMART is preventing exposure of fetuses to isotretinoin.
• Pharmacists will dispense isotretinoin only upon presentation of a prescription with the special Accutane Qualification Sticker. Pharmacists will dispense a maximum one-month supply of isotretinoin, fill prescriptions within seven days from the date of “qualification,” and provide a Medication Guide (FDA-approved written information for patients) with each isotretinoin prescription. Requests for refills (i.e. more isotretinoin without a new prescription) and phoned-in prescriptions will not be filled.

When the manufacturer of a drug is given primary responsibility to ensure the safe and effective use of that drug, the public remains at an unacceptable level of risk.

What You Can Do

You or your children should only use isotretinoin in the case of severe recalcitrant nodular acne after other safer acne treatments have been tried and failed.

Exposure of an unborn fetus to isotretinoin is a serious adverse event and should be reported directly to the FDA MedWatch Program along with other adverse reactions.