New warning about acutane and birth defects

FDA Consumer, Oct, 1988 by Judith Willis

New Warning About Accutane and Birth Defects

Some likened the decision asked of FDA to that required of the biblical Solomon when two women seemed to have equal claim to being mother of the same child.

The issue before FDA, however, was not one of parentage, but whether a drug that has the ability to clear a very severe and disfiguring form of acne should be taken off the market because it also carries a high risk of causing a deformed baby or miscarriage if taken by a pregnant woman.

The name of the drug is Accutane (generically called isotretinoin). The issues surrounding it could serve as a basis for a course in medical ethics. Summarized, these issues are:

* A relative of vitamin A (see accompanying article), Accutane was known to cause birth defects in animals and suspected of causing them in humans even before it was approved by FDA in 1983. Although the labeling has always forbidden use of the drug during pregnancy, such use has nevertheless occurred. Marketing experience with the drug indicates that Accutane causes birth defects in about one out of every four exposed fetuses.

* The condition fr which the drug was approved, severe recalcitrant cystic acne unresponsive to other therapy, is much more common in males than in females. Yet 40 percent of the prescriptions are written for women, virtually all of whom are of childbearing age. The primary reason given for this is that women seek treatment for thsi condition more often than men.

* Accutane is the only drug that can clear this severe and disfiguring form of acne. Other drugs approved to treat the same condition must be taken for extended periods and, when stopped, the condition usually reappears. But with Accutane, most patients need to take the drug for only a few months. When the drug is discontinued, the acne usually does not return.

* Birth defects continued to occur despite repeated revisions of the labeling, letters to physicians from the manufacturer, Hoffmann-La Roche, and articles in the FDA Drug Bulletin (a publication sent to more than 1 million health professionals) that the drug should not be used by women of childbearing age unless they were using an effective form of contraception. Miscarriages (technically called spontaneous abortions when occurring in the first three months of pregnancy) also continued to occur at a rate substantially higher than in the general population. In addition, there has been an increased rate of elective abortion among women taking Accutane, apparently resulting from the wish to avoid giving birth to a deformed child.

To publicly consider these issues, FDA convened a meeting last April of its Dermatologic Drugs Advisory Committee, a panel of experts from outside the agency. Highly knowledgeable and respected scientists lined up on both sides of the issue. Representatives from the federal Centers for Disease Control (part of the Public Health Service) and the American Academy of Pediatrics recommended that the drug be withdrawn from the market. Consumer advocates proposed severe restrictions. Spokespersons from the American Academy of Dermatology, representing skin specialists (who write 90 percent of all Accutane prescriptions), emphasized its therapeutic value and the physical and psychological scarring, along with the social ostracism, that patients with severe cystic acne often endure. They recommended continued marketing with a number of restrictions.

Proponents of keeping the drug on the market showed slides of patients with disfiguring acne, not only on the face but also on the shoulders, arms, back, and chest.

Proponents of severely restricting or totally banning the drug showed slides of babies with the birth defect syndrome known to be associated with the drug: mishapen head, lack of ears or ears placed low next to a too-small jaw, and cleft palate. They also described the defects of the brain and heart and explained that the drug does the most damage to the fetus in the early weeks of pregnancy, often before a woman realizes she is pregnant.

How was FDA to choose between protecting the unborn and healing patients with a disfiguring physical problem?

Should the agency allow a drug to remain on the market that continued to be a cause of birth defects despite warnings that it not be used in women who were pregnant or who might become pregnant?

On the other hand, could FDA ethically remove from the market a drug that had the capacity to clear up a disfiguring condition when no other marketed drug was as effective?

Fortunately, FDA had a solution available to it that was not available to Solomon: compromise.

Taking into account advice from consumer and professional organizations, the agency and Hofmann-La Roche have been hammering out further restrictions and unprecedented labeling warnings in the expectation that these will insure the appropriate use of the drug and, thus, the elimination of birth defects associated with its use.

One aspect of this plan is the inclusion, in the patient information labeling, of a drawing of a baby with the syndrome of deformities associated with Accutane use. The drawing is meant as an attention-getter and as a deterrent to women who might otherwise take lightly the warning not to take the drug unless they are using an effective form of contraception.