Accutane: The Benefits and Risks of a Breakthrough Acne Drug

by Food and Drug Administration (FDA)

Acne plagued Julie Harper throughout high school and college. She depended on makeup and wore her hair down over the side of her face. She gave up chocolate and french fries, only to find that neither made a difference. And she went through medicine after medicine, from over-the-counter creams to oral antibiotics.

These were not occasional pimples that vanish after a couple of days. This acne covered her face and left scars on her neck. "I had tried everything and felt frustrated all the time," says Harper, now a physician and assistant professor of dermatology at the University of Alabama-Birmingham — a career she chose due in large part to her struggle with acne.

Harper finally found a successful treatment nine years ago at the age of 22. She took a drug called isotretinoin (trade name Accutane) and watched her skin improve in just a couple of months. By the third month, her acne had disappeared. She says with clearer skin came more self-confidence and higher self-esteem.

Considered the biggest breakthrough in acne drug treatment over the last 20 years, Accutane is the only drug that has the potential to clear severe acne permanently after one course of treatment. One course, which is typically five months, results in prolonged remission of acne in up to 85 percent of patients. A member of a class of drugs known as retinoids, Accutane is highly effective. But it doesn't work for everyone, and some patients need more than one course of treatment. Dr. Harper took a second course of Accutane one year after the first and has been free of severe acne ever since, now only occasionally using a topical medication.

No other acne medicine works as well for severe acne. Patients generally have to keep using other medications because they only suppress acne temporarily. But as powerful as Accutane can be in improving patients' lives, its adverse effects can be just as powerful. The drug is known to cause miscarriage and severe birth defects. Patients taking Accutane may develop potentially serious problems affecting a number of organs, including the liver, intestines, eyes, ears, and skeletal system. And some patients taking Accutane have developed serious psychiatric problems, including depression. More rarely, patients have developed suicidal behavior and killed themselves.

Because it is a high-risk drug, Accutane should be reserved for cases of "severe recalcitrant nodular acne," according to the product's labeling. This type of acne is resistant to standard acne treatment, including oral antibiotics, and is characterized by many nodules or cysts — inflammatory lesions filled with pus and lodged deep within the skin. These lesions can cause pain, permanent scarring, and negative psychological effects.

"Sometimes people tend to dismiss the impact of acne because it's not life-threatening, says Kathy O'Connell, MD, PhD, a medical reviewer for Accutane in FDA's division of dermatologic and dental drug products, Center for Drug Evaluation and Research (CDER). "But patients with severe acne know all too well the very real suffering caused by this disfiguring disease."

FDA approved Accutane in 1982, and since then, about 5 million people in the United States and 12 million worldwide have been treated with it, according to its manufacturer, Hoffmann-La Roche of Nutley, N.J. The number of patients taking the drug has increased, and half are females, most of whom are in their childbearing years (age 15-44). Because of concern about the drug's risks, FDA continues to evaluate Accutane and work with the manufacturer to maximize safe use of the drug.

Warning about Pregnancy Risks

When FDA approved Accutane, the drug was known to be teratogenic — able to cause birth defects. It was designated as Category X, meaning that it must be avoided under all circumstances during pregnancy. Nursing mothers also should not use Accutane.

Though not every fetus exposed to Accutane becomes deformed, the risk of birth defects among pregnant women is extremely high. These defects include hydrocephaly (enlargement of the fluid-filled spaces of the brain) and microcephaly (small head), heart defects, facial deformities such as cleft lip and missing ears, and mental retardation.

Reports in the literature suggest that about 25 to 35 percent of babies will suffer a malformation after exposure, and that doesn't account for other defects, such as learning disabilities, that aren't detectable at birth. Miscarriages and premature births have also been reported.

Though FDA approved labeling in 1982 that warned Accutane should not be used in pregnant women, reports of severe birth defects associated with the drug began to arrive in June 1983. Over the following years, a series of labeling changes and letters to pharmacists and prescribers of the drug stressed pregnancy warnings and sought to increase awareness about reported malformations.

Then, after an FDA review of pregnancy exposures to Accutane, Roche launched the Pregnancy Prevention Program (PPP) in late 1988 to further educate women using Accutane and their physicians about the dangers. The goal was to ensure that prescriptions would only be given to women with severe recalcitrant nodular acne who could comply with contraceptive requirements.

Roche sent PPP kits to physicians and encouraged them to review pregnancy prevention materials with patients before starting the drug. Materials included a contraceptive booklet, checklists to help assess whether patients could adhere to the drug's requirements, and consent forms that patients sign to acknowledge their understanding of the risk of birth defects. Roche also set up a toll-free line, made contraceptive information available in 13 languages, and offered to pay for contraceptive counseling and pregnancy testing by a specialist.

To further reinforce pregnancy prevention, Roche began packaging Accutane in blister packs that include red and black warnings, along with a drawing of a malformed baby and the "Avoid Pregnancy" symbol.

Even though Accutane's labeling recommended use of two reliable forms of contraception, there have been reports of pregnancies occurring in patients who used hormonal contraception, including pills, injectables, and implantables, while taking Accutane. Accutane's labeling was updated in the summer of 2000. One change emphasized the need for two reliable forms of contraception for at least one month before taking Accutane, during treatment, and for one month after discontinuing Accutane, even when one of the forms of contraception is hormonal.

About the Author

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