In response to calls for the withdrawal of Accutane, Roche proposed a patient education program on the risk of birth defects, that included patient materials and informed consent forms for women to sign before receiving the drug.
In September, 2000, because the number of prescriptions to women of child-bearing age had tripled from 70,000 a year in 1989, to almost 210,000 in 1999, there was more concern over the increasing number of pregnant women exposed to the drug so FDA's Dermatologic and Ophthalmic Drugs Advisory Committee held a meeting to discuss what measures might help prevent further fetal exposure.
Public Citizen once again testified at the hearing and recommended that a Patient Medication Guide be issued and again urged the FDA to remove Accutane from the market unless restrictions were implemented and proven to be effective.
The "System to Manage Accutane Related Teratogenicity," or SMART program, was implemented in April 2002, and required women to have 2 pregnancy tests before starting on Accutane, to get a pregnancy test each month before refilling a prescription, to receive counseling on birth control, and to agree to use two forms of birth control simultaneously while using Accutane.
The Adverse Event Reporting System (AERS) is a computerized database of post-marketing adverse events for all approved drugs, designed to support the FDA's post-marketing safety surveillance program.
The reports in AERS are evaluated by agency reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to detect safety signals and to monitor drug safety.
During the December 11, 2002 hearing, Roche claimed that only 2,300 pregnancies had occurred among Accutane users since its introduction in 1982. However, Congressman Bart Stupak (D-MI), refuted that assertion, by citing a 1999 company report indicating that in a single 3 month period that year, 93 unwanted pregnancies were reported and 42 abortions occurred.
According to Dr Janet Woodcock, Director of the CDER at the hearing, AERS contained almost 23,000 adverse event reports for Accutane from the time of its approval in 1982 to December 2002.
For 2002 thus far, she said, AERS contains just over 1,100 adverse event reports. During 2002, she told the panel, the five most frequently reported reactions are, in descending order, depression, pregnancy, induced abortion, suicidal ideation, and headache.
Dr Woodcock explained that the Office of Drug Safety (ODS) within CDER maintains a quarterly cumulative count of reports of Accutane-exposed pregnancies and outcome, if known, based on Roche's quarterly submission.
The latest update as of June 2002, she said, "shows a total of 2,350 Accutane-exposed pregnancies and 172 babies born with a congenital defect or anomaly in the U.S. since the product was approved in 1982."
According to testimony by Dr Nancy Green, medical director of the March of Dimes Birth Defects Foundation, Associate Professor of Pediatrics and Cell Biology at the Albert Einstein College of Medicine, the major birth defects include a syndrome that includes mental retardation, hydrocephalus, microcephaly, cleft lip and palate, cardiovascular anomalies, and ear and limb abnormalities.
Lynn Martinez, Manager of the Organization of Teratology Information Services (OTIS), a national group that tracks prenatal birth defects exposure, informed the committee that OTIS was still receiving reports from women who had become pregnant while taking Accutane, despite the SMART program.
To measure compliance with the SMART program, researchers surveyed 34 women who had called a member service of the OTIS between April 2002 and September 2004 because they had become pregnant while taking isotretinoin.
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