The Return of Thalidomide

Abstract

Thalidomide, the drug that caused a worldwide epidemic of serious birth defects in the late 1950s and early 1960s, was recently approved by the US Food and Drug Administration (FDA) for use in treating the skin disease erythema nodosum leprosum, a complication of leprosy. The drug has also shown promise in the treatment of other serious diseases. If thalidomide is eventually approved for use in the US and other countries for treatment of diseases more prevalent than erythema nodosum leprosum, or if use of the drug for non-approved indications becomes widespread, hundreds of thousands of women with childbearing ability could be treated. If this should happen, can we prevent another epidemic of birth defects?

In an effort to prevent fetal exposures to thalidomide, the FDA mandated a comprehensive programme to regulate prescription, dispensing and use of the drug. The programme is designed to require registration of all participating pre-scribers, pharmacies and patients. It also requires use of effective methods of contraception and periodic pregnancy testing of all patients with childbearing ability during treatment. Prescribers are directed to counsel both female and male patients on the risks, benefits and proper use of the drug, as well as on the proper use of contraceptives during treatment. The patient is required to sign an informed consent form before beginning treatment. Prescription and dispensing of thalidomide will be tightly controlled. A thalidomide registry will monitor prescription, dispensing and use of the drug, and will investigate all reported fetal exposures.

This mandatory, but untested, programme promises to be effective at preventing fetal exposures to thalidomide, provided that patients, prescribers and pharmacists comply with all of its provisions. However, even if the programme proves to be successful in the US, there is concern that thalidomide may eventually be widely used in countries that may not require such stringent controls. In Brazil, where thalidomide is commercially available for treatment of leprosy patients, 33 cases of thalidomide embryopathy have already been reported in the literature. Even in countries that may tightly regulate the distribution and use of thalidomide, some patients may obtain the drug through black market sources. Should these events occur, many cases of thalidomide-induced birth defects could appear. Therefore, there is a need to develop nonteratogenic analogues of thalidomide that can provide effective treatment for erythema nodosum leprosum and other serious conditions without increasing the potential for another epidemic of thalidomide-related birth defects.