FDA Says Women Fail to Heed Warnings On Powerful Acne Drug
By ANNA WILDE MATHEWS
Staff Reporter of THE WALL STREET JOURNAL
Strict measures adopted to reduce the risk of birth defects linked to the acne drug Accutane appear to be having little effect.
The number of women who took versions of the drug while pregnant barely budged in the first year of the new restrictions imposed in April 2002, even though about 23% fewer prescriptions for Accutane and its generic rivals were being written. Accutane, which has been on the market for more than two decades, is perhaps the most powerful and effective treatment for severe acne. But it use has long been debated because of its impact on pregnancies as well as possible links to depression.
The new data, disclosed by the Food and Drug Administration in advance of an advisory committee meeting on the acne drug next week, underscore the challenges facing the agency as it tries to keep useful, though potentially dangerous, drugs on the market. Increasingly, the FDA is turning to more aggressive measures that can limit the ways doctors prescribe and pharmacists provide such medicines.
Within the next several months, the agency is expected to propose its first guidelines for drug risk-reduction efforts. The issue is already sparking debate among drug companies, doctors and pharmacists concerned about restrictions on distribution and prescribing. Because the FDA doesn't regulate the practice of medicine or the pharmacy industry, it typically has to negotiate risk-reduction measures with manufacturers as part of the drug-approval process.
Traditionally, the FDA's safety measures for drugs with serious side effects have focused on warnings included in drugs' labels and letters sent to doctors. But after a series of high-profile drugs had to be removed from the market in the late 1990s -- often after physicians failed to adhere to agency cautions -- the FDA has moved toward efforts that try to influence how drugs are handled in the marketplace.
"The traditional elements of labeling aren't always enough," says Steven Galson, acting director of the FDA's Center for Drug Evaluation and Research. But "we don't want to put on more restrictions than are necessary." One concern for the FDA is whether restrictions on risky medicines can create incentives for doctors to use different drugs that may have their own drawbacks.
The agency and drug makers turn to such measures for only a tiny number of drugs. Thalidomide, known for its risks to pregnant women, was approved in 1998 to treat leprosy-related symptoms but with very stringent antipregnancy requirements. Lotronex, a treatment for irritable bowel syndrome that was pulled from the market in 2000 after being tied to serious intestinal problems and some deaths, was reintroduced by GlaxoSmithKline PLC with new restrictions in 2002.
Accutane, whose generic name is isotretinoin, was one of the earliest examples of efforts to control a drug's risk. Approved in 1982, the drug's label warned it was not to be taken by pregnant women. Over the years, Accutane's maker, Roche Holdings AG, added measures including videos about the risks and blister packs with a warning graphic.
In April 2002, as use with pregnancies continued, Roche started a new program. Doctors would paste special yellow stickers on the prescriptions to verify that patients had taken a pregnancy test. Pharmacists were supposed to only fill prescriptions with stickers. Makers of generic Accutane, which started being approved in November 2002, provided similar initiatives. Patients were asked to take part in surveys on the results.
But the new FDA information on Accutane and its generic rivals shows that in the 12 months after the new restrictions started, 120 women were reported to be pregnant while taking Accutane, either because they were pregnant when they started or conceived while taking it.
Those numbers compared with 127 reported pregnancies in the previous 12 months, when the restrictions were looser. The FDA's conclusion: Only "minimal or no improvement" over the old measures, the agency said in its briefing documents. The agency now suggests it may consider adopting more stringent steps "to further reduce the likelihood" of pregnancies.
Roche, in a document submitted to the FDA, is recommending its own stricter measures. Generics makers submitted a document saying they "agree in principle" with the brand maker. In a statement, Roche said it "generally agrees with FDA that the numbers of pregnancies do not reflect an appreciable decrease" after the restrictions begun in 2002. "We always want to work toward the ultimate goal of no woman getting pregnant or starting Accutane while pregnant," says Susan Ackermann Shiff, head of global risk management for the company.
One goal of the Accutane risk-reduction efforts was for 60% of patients to participate in user surveys. According to the FDA data, only about 22% to 26% did so.
However, the plan met another key goal. Ninety percent or more of isotretinoin prescriptions had stickers indicating the physician had conducted a pregnancy test. Those results may be skewed, though, because many major pharmacy companies asked to be removed from the study. Overall, 91% of apparently fertile women had a pregnancy test before they started taking isotretinoin. Of those who said they had a sticker on their prescriptions, 9% said they didn't get a pregnancy test.
The FDA says that there were 325 pregnancies involving users of the acne drug reported between April 1, 2001, and August 15, 2003. The agency said in about half the cases, it doesn't know the results of those pregnancies. Of the remainder, FDA says, there were 23 spontaneous abortions or ectopic pregnancies and 113 elective abortions. Of the 29 babies born, seven of those involved reported abnormalities, including cases of heart, kidney and facial anomalies.
Write to Anna Wilde Mathews at anna.mathews@wsj.com
Updated February 18, 2004
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