Controversial Acne Drug Could Get Popped (With More Regulation)

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Dec. 4, 2000 (Washington) -- Recent reports suggesting the popular acne drug Accutane (isotretinoin) may trigger depression and suicide have spurred a congressional hearing Tuesday to investigate whether tighter controls need to be placed over the drug. But experts are cautioning that, despite the drug's side effects, further restrictions on its use and distribution could, in effect, lead to the drug's withdrawal.

Accutane was approved in 1982 as a treatment for severe acne. It is the only drug proven to effectively control severe cystic acne, the most serious form of this skin disease.

The congressional hearing follows a claim by Rep. Bart Stupak (D-Mich.) that Accutane was responsible for his son's recent suicide. At a press conference, Stupak called upon the drug's maker, Roche, to conduct independent studies of Accutane's mood-altering effects. He also called for enhanced surveillance over the drug.

According to the FDA, Accutane has been associated with about 44 suicides since 1983. But the agency says there is not enough data to establish a definite link, although the drug does appear to have mood-altering effects.

Calling the suicides "spontaneous," Roche says they simply reflect "the multiple risk factors in the adolescents and young adults afflicted with the disfiguring disease." The company also notes that the drug's label already warns that Accutane has been associated with depression and suicide, although a clear link has yet to be established.

Still, some experts fear that Tuesday's hearing might lead to further restrictions because of Accutane's other well-known side effect: The drug is known to cause birth defects.

Birth defects occur in an estimated one of every four babies born to women who take Accutane while pregnant. But the number may be higher, some experts believe, since about 40% of the pregnancies that occur among women on Accutane end in a miscarriage.

As a result, the FDA has required the company to make a number of labeling changes since the drug's approval, to the point where few drugs are as explicitly labeled. But despite all the labeling changes, new patient information inserts, and "Dear Doctor" letters alerting doctors to these changes that the agency has required over the years, the absolute number of pregnancies among women on Accutane has remained largely unchanged.


At an FDA meeting in September, a panel of medical experts indicated that while the reported psychiatric events do not appear to be of major concern, the ongoing pregnancies are of particular concern considering that the use of Accutane has tripled since its approval. The panel commended Roche for its ongoing efforts to educate physicians and patients, but then recommended that a mandatory registration program be created to ensure that patients use the drug as directed. Roche wants a voluntary registration program.

At present, Roche already is phasing in a Targeted Pregnancy Prevention Program directly aimed at those women who, for whatever reason, fail to comply with the mandatory pregnancy prevention provisions required under the prescription. Roche also has prepared a checklist for doctor and patients, which includes a 24-hour contraceptive counseling hotline. And the company has begun shipping pregnancy tests to physicians and now plans to send marketing representatives to about 97% of the prescribing doctors as well.

The FDA has yet to act on the panel's recommendations for Accutane. But the agency recently has taken a number of actions to ensure the proper use of other controversial drugs that, in one instance, eventually resulted in the drug's withdrawal.

The FDA recently attempted to restrict the distribution of Glaxo Wellcome's Lotronex (alosetron), a treatment for irritable bowel syndrome. Lotronex has been associated with 49 cases of a rare, but potentially serious side effect called ischemic colitis. But rather than accept the FDA's proposed restrictions, the British drug maker decided to withdraw the drug voluntarily, saying that the agency's proposed restrictions were equivalent to a withdrawal.

Experts caution that restricting Accutane to only a set of registered pharmacies and physicians could in effect lead to a similar result.

"As dermatologists, we strongly believe that limiting access to [Accutane] is a disservice to patients and erodes the patient-physician relationship," said Richard Scher, MD, president of the American Academy of Dermatology (AAD), following the FDA panel meeting in September. "Education, not regulation, is the key to safe use of this drug to protect women of childbearing age."


"It's not workable," adds David Pariser, MD, FACP, chief of dermatology at the Eastern Virginia Medical School in Norfolk. A registry of all the doctors and pharmacies that need access to Accutane simply would be impossible to generate and maintain, he argues.

Pariser, who will appear at the congressional hearing as a representative of the dermatology association, adds that a registry could drive patients to seek Accutane by other means. "Our fear is that patients will turn to the Internet" and other unreliable sources to get the drug, he tells WebMD.

The American Medical Association (AMA) may soon back the AAD's position. At the AMA House of Delegates interim meeting, currently underway, the AAD is lobbying for the AMA to support encouraging the FDA to seek educational, not regulatory, solutions. The proposed mandatory registry would erode the relationship between patients and their physicians and diminish patient confidentiality, the AAD proposal warns.

But certain influential citizen groups already are uniting in favor of the restrictions. "It is inexcusable that the company has gone for so long without restricting the use of Accutane," says Sidney Wolfe, MD, a director of the consumer watchdog group Public Citizen, the group influential in getting the controversial diabetes drug troglitazone (Rezulin) off the market earlier this year.

Some lawmakers also believe that the FDA and Roche have underestimated Accutane's ability to cause depression and suicide. According to Stupak, his office has determined that over the last two-and-a-half years there have been about two suicides per month that can be associated with Accutane use.

While this does not confirm that Accutane causes depression or suicide, it is ample proof that patients should at least receive additional information concerning these risks, add representatives of the House Committee on Government Reform, which will be hosting the congressional hearing Tuesday.

The hearing is titled "Is Teen Acne Drug Linked to Depression and Suicide?" Besides testimony from experts, the committee is scheduled to hear from family members of teens that committed suicide while on Accutane, as well as federal regulators such as Janet Woodcock, MD, director of the FDA division responsible for prescription drugs.

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