Feb. 27, 2004 -- An FDA advisory panel is recommending a stricter tracking program for women who take the acne drug Accutane, as well as generic and other versions of the drug isotretinoin. The recommendation follows a report that the current industry-run program has failed to lower rates of unplanned pregnancies and reduce the risk of birth defects in babies born to women taking the drug.
Manufacturers and regulators unveiled data showing that more than 200 women took the drug, also sold under the generic name isotretinoin, while pregnant. The pregnancies came after the initiation in April 2002 of a program intended to prevent women from becoming pregnant while taking the drug or from using the drug if they are already pregnant.
The program, known as SMART (System to Manage Accutane Related Teratogenicity), was developed because data show that despite extensive warnings, pregnant women continue to receive Accutane prescriptions and women continue to become pregnant while taking Accutane.
Manufacturers told regulators that they were willing to move to an even stricter tracking program in an attempt to stave off further potential fetal exposures. An FDA advisory panel voted 16-8 on Friday to recommend a mandatory registry for all Accutane users. In addition, physicians and pharmacists must document that women are complying with pregnancy prevention measures.
The FDA is not bound by its advisory committees' recommendations but usually follows them.
Potential for Birth Defects
Accutane has been prescribed to millions of adolescents and adults and is deemed a highly effective treatment against recurrent and severe acne.
However, the drug carries heavy FDA warnings because it can cause organ damage or mental retardation in fetuses.
As part of the current risk management program, the prescriber must obtain an informed consent from the patient, counsel the patient, and provide educational materials as well as encourage enrollment in the voluntary Accutane Survey.
Women are supposed to have two negative pregnancy tests before receiving a prescription for the drug, which contains a qualifying sticker on the prescription. The woman must also use two forms of contraception during therapy.
Pharmacists dispense Accutane only if a valid sticker is in place and only within one week of the date on the prescription, and refills and dispensing of greater than 30 days' supply are not allowed.
But Accutane maker Hoffmann-La Roche Inc. reported that 183 women took the drug while pregnant during its strict tracking program, compared with 150 in the year before. Three generic manufacturers reported 19 more cases since December 2002 while using identical tracking programs.
FDA officials warned that many more women have probably become pregnant while on the drug but have not reported it.
"We believe these ... cases represent a fraction of what occurs," says Marilyn Pitts, PharmD, a safety evaluator with the FDA's office of drug safety.
The majority of the pregnancies ended in spontaneous or elective abortions, and regulators have received a handful of reports of birth defects.
Data show that women usually became pregnant while already taking isotretinoin, suggesting that they did not stick to warnings to use two forms of contraception while on treatment.
Patients are displaying "a pattern of failure to comply with the educational messages they receive," says Martin H. Huber, MD, vice president and global head of drug safety at Hoffmann-La Roche.
Stricter Tracking Standards
The company and three generic manufacturers will start stricter company-run tracking standards for women taking isotretinoin, including the distribution of unique identification numbers for all patients.
The numbers would be used in a single, centralized database including qualified doctors, pharmacists, and their patients. Doctors would have negative pregnancy tests confirmed and patients would be required to hear repeated educational messages before they could receive 30-day refills.
"If they don't access the system properly, they cannot get the product," Huber says.
Other groups called on the FDA to take stricter action, citing continued pregnancies while women take isotretinoin. The consumer group Public Citizen called on regulators to take the drug out of regular distribution and make it available only under very tightly regulated conditions.
The tracking programs are "clearly a failure," says Sydney M. Wolfe, director of Public Citizen's health research group. He called on regulators to stop "needless use of a drug that each year causes the need for hundreds of abortions" and birth defects.
The March of Dimes called on the FDA to mandate stricter tracking programs for the drug. The group released a statement warning that it would call for a ban on oral forms of isotretinoin if the FDA does not mandate stricter tracking standards for women.
The committee is expected to vote Friday on whether to back the new program or recommend that the FDA take stricter action.
Peter A. Gross, MD, the chairman of the FDA's drug safety and risk management advisory committee, told WebMD that cases of pregnancy in women on isotretinoin are "a tragedy."
"You can't make people do what they ought to do," he says.
Gross notes that the drugmaker's proposal for a tighter tracking program is similar to what the committee recommended to the FDA in 2000.