Compliance Plan Set for Teratogenic Acne Drug


In a move that caught many in the medical community by surprise, the Food and Drug Administration last month announced a comprehensive—and mandatory—risk management program for the teratogenic acne drug isotretinoin that demands complete compliance by year's end.

The program, called iPLEDGE, will require registration and ongoing compliance by all physicians and patients by Dec. 31, 2005. The iPLEDGE initiative replaces Roche's voluntary SMART program for Accutane and similar programs for the four generic versions of isotretinoin.

The FDA informed physicians in November 2004 that SMART would be replaced. “This is a system that has long been coming, and some would say is long overdue,” said Sandra Kweder, M.D., deputy director of the FDA's Office of New Drugs.

The program's implementation will be incremental, starting with the Oct. 31, 2005, deadline for registration of wholesalers and pharmacies to obtain isotretinoin from a manufacturer. Prescribing physicians and their patients will then have two more months to be registered and in full compliance. Under the program, wholesalers of Accutane or the four currently approved generic equivalents will distribute isotretinoin only to pharmacies that have registered with the safety program and continue to demonstrate ongoing compliance.

Those pharmacies will dispense prescriptions only when the prescribing physician has registered the individual patient being treated and certified that the patient has been informed of the teratogenicity risks and has had two negative pregnancy tests (a screening test and a confirmatory test) performed by a laboratory or in the physician's office. Patient registration will be done over the Internet or by phone.

Patients must also register themselves and sign a consent form agreeing to use two forms of birth control while on the drug. Patients will be required to have repeat pregnancy testing every month while they are on the drug and another 1 month after they stop. Prescriptions will need to be filled within 7 days of pregnancy testing.

The package insert and the patient informed consent form have been updated and now contain a new warning that there have been suicides reported in patients taking isotretinoin. Both inform patients about what signs to watch for and tell them to contact their health care provider if they recognize any of those signs.

The new program replaces the old, required program for Accutane known as SMART (System to Manage Accutane Related Teratogenicity) and the other similar programs for the generic products. Under SMART, physicians who wanted to prescribe Accutane needed to complete an education program to obtain the yellow stickers that needed to be attached to the paper prescriptions for pharmacies to fill the prescriptions. When attaching a sticker, the physician was also required to register the patient and to certify that the patient had undergone pregnancy testing and that the results were negative.

FDA determined that the SMART program needed to be replaced with a more stringent program because data from the first 2 years of the program, which went into effect in 2002, showed that it had not significantly reduced the rate of pregnancies occurring in patients on isotretinoin, which was its aim. Some also claimed that not all physicians were being fully compliant with the pregnancy testing requirement of the program.

Moreover, too few patients were signing up with the voluntary patient registry that was a part of the program.

Physicians can access the iPLEDGE program on the Internet by going to

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