Off-Label Promotion, On-Target Sales

Adriane Fugh-Berman; Douglas Melnick


PLoS Med. 2008;5(10) 

In This Article

Risks and Benefits for Patients

Off-label use is sometimes unavoidable; three-quarters of marketed prescription drugs have no labeling indications for children, a population only recently included in clinical trials.[1] Pregnant women are also routinely excluded from studies, so most drug treatment during pregnancy is off-label.

Some off-label use is demonstrably beneficial. For example, in the United States, misoprostol, a prostaglandin, is approved only to prevent ulcers. However, misoprostol is widely used off-label for ripening the cervix, inducing abortion, and other indications, and more than 200 studies involving more than 16,000 pregnant women support the use of misoprostol in obstetrics.[2]

Pregnant women and children, however, do not account for most off-label use. In 2001, 150 million off-label prescriptions were written -- 21% of all prescriptions written for 160 common medications in the US. About three-quarters (73%) of off-label prescriptions were written for conditions for which there was little or no scientific support for efficacy.[3] Up to 75% of drug use in cancer care, and about 90% of drug use in rare diseases, is off-label.[1]

Off-label use of drugs has been associated with serious adverse effects. For example, Duract (bromfenac), an analgesic, was approved only for treating acute pain, and only for short-term use (less than ten days). However, some physicians prescribed Duract off-label for longer durations. Duract caused liver failure, and was withdrawn from the market less than a year after approval.[4] The appetite suppressant Pondimin (fenfluramine), approved for short-term use, was widely prescribed with phentermine and used long-term. The off-label combination "fen-phen" caused valvular heart disease.[4,5] In children, off-label use of drugs is associated with an increased number and severity of adverse effects.[6]