Thalidomide--Will Physicians Comply with FDA Rules?

By Ronald L. Scott

The Food and Drug Administration (FDA) recently approved the drug Thalidomide for the treatment of a condition affecting fewer than 100 people in the United States. Patients with Hansen’s disease (leprosy) may benefit because the drug effectively treats painful lesions known as erythema nodosum leprosum by suppressing a chemical in the body called tumor necrosis factor alpha. The FDA’s approval of Thalidomide is controversial because the drug caused severe birth defects in the 1960s when used to treat morning sickness in pregnant women. Ironically, the FDA has never previously approved use of Thalidomide. The birth defects in other countries nonetheless led to laws in the United States that strengthened the FDA, and its refusal to approve the drug in the 1960s was lauded internationally.

When the FDA first approves a drug, its labeling is also approved, signifying that the FDA has determined that the drug is both safe and effective to treat the conditions stated in the labeling. However, physicians are allowed to prescribe drugs for conditions not listed in the FDA-approved labeling, i.e., off-label use. Even though Thalidomide is dangerous when misused, physicians are free to prescribe it for other uses even without approval from the FDA. One argument for such "off-label" use is that it is expensive and time-consuming for a pharmaceutical company to amend a drug’s labeling. Essentially, the company must conduct sufficient clinical trials to convince the FDA that a drug is safe and effective to treat a new condition to be included in the labeling. Thalidomide shows promise for treating severe mouth ulcers that some people with AIDS develop, and may even help fight the wasting associated with AIDS.

In approving Thalidomide, although the FDA has not sought to restrict its use to the approved labeling, it has enacted innovative safeguards. Both physicians who prescribe the drug and pharmacists who dispense it must register with the FDA and receive training on how to warn patients about the drug’s dangerous side effects. Female patients must undergo a pregnancy test before receiving the drug and have periodic pregnancy tests throughout their use of the drug. Women must also agree to utilize two forms of contraception, and men will be advised to use condoms when taking the drug, even though it is not known whether Thalidomide passes through sperm.

The FDA’s concern that the drug may be misused is not without foundation. The heart drug Posicor caused several deaths due to interaction with cholesterol-lowering drugs, even though physicians were warned about the interactions. The FDA and the drug’s manufacturer eventually withdrew Posicor from the market. More recently, the painkiller Duract was withdrawn when it became clear that physicians were prescribing it for more than the 10 days specified in the drug’s labeling. In approving Thalidomide with the extraordinary safeguards on prescribing and dispensing, the FDA has sought to balance concerns for safety with a physician’s ability to prescribe the drug for a condition not specified in the drug’s labeling.