However, they also showed that the compound was likely to cause birth defects, so in light of the events around thalidomide, Roche abandoned the product. In 1979, the New England Journal of Medicine published an article demonstrating the drugs effectiveness as a treatment of cystic and conglobate acne on fourteen patients, thirteen of which experienced complete clearing of their disease. Roche resumed work on the drug. In clinical trials, subjects were carefully screened to avoid including women who were or might become pregnant. Roches New Drug Application for isotretinoin for the treatment of acne included data showing that the drug caused birth defects in rabbits. The FDA approved the application in 1982. Scientists involved in the clinical trials published articles warning of birth defects at the same time the drug was launched in the US, but nonetheless, isotretinoin was taken up quickly and widely, both among dermatologists and general practitioners. Cases of birth defects showed up in the first year, leading the FDA to begin publishing case reports and to Roche sending warning letters to doctors and placing warning stickers on drug bottles, and including stronger warnings on the label. Lawsuits against Roche started to be filed. In 1983 the FDAs advisory committee was convened and recommended stronger measures, which the FDA took and were that time unprecedented: warning blood banks not to accept blood from people taking the drug and adding a warning to the label advising women to start taking contraceptives a month before starting the drug.
Isotretinoin, also known as 13-cis-retinoic acid and sold under the brand name Accutane among others, is a medication primarily used to treat severe acne. It is also used to prevent certain skin cancers (squamous-cell carcinoma), and in the treatment of other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. It is a retinoid, meaning it is related to vitamin A, and is found in small quantities naturally in the body. Its isomer, tretinoin, is also an acne drug. The most common adverse effects are dry lips (cheilitis), dry and fragile skin, and an increased susceptibility to sunburn. Uncommon and rare side effects include muscle aches and pains (myalgias), and headaches. Isotretinoin is known to cause birth defects due to in-utero exposure because of the molecules close resemblance to retinoic acid, a natural vitamin A derivative that controls normal embryonic development. It is also associated with psychiatric side effects, most commonly depression but also, more rarely, psychosis and unusual behaviours. Other rare side effects include hyperostosis and premature epiphyseal closure, which have been reported to be persistent. In the United States, a special procedure is required to obtain the pharmaceutical. In most other countries, a consent form is required which explains these risks. In other countries, it is prescribed like any other medicine from a dermatologist (after proper blood tests). Women taking isotretinoin must not get pregnant during and for one month after the discontinuation of isotretinoin therapy.