Off-Label Drug Use: What You Need to Know

A Risky Practice?

There is debate about off-label drug use. Doctors emphasize that off-label prescribing has its place in medical practice, but they also admit that using a drug off-label can raise the risk of lawsuits should a patient have unwanted or bad side effects.

"Off-label prescribing can expose patients to risky and ineffective treatments," medical ethics professor Rebecca Dresser and Joel Frader, MD, write in the fall 2009 issue of The Journal of Law, Medicine & Ethics.  

Fen-Phen is one of the best examples of off-label use with a poor outcome. The FDA approved medications fenfluramine hydrochloride and phentermine hydrocholoride as individual, short-term treatments for obesity. But doctors eventually began prescribing the two drugs together after an article describing the cocktail's dramatic weight loss effects appeared in a medical journal and numerous mainstream publications.

That off-label drug combination had devastating results: Many patients ended up with severe, and potentially deadly, heart valve damage, an outcome that triggered a multi-billion dollar lawsuit. In 1997, the FDA ordered Fen-Phen off the market.

Although some off-label therapies can be beneficial and even lifesaving for some patients, in most cases, there is little or no scientific evidence to prove they work. In a recent commentary in the Archives of Internal Medicine, three scientists from the National Institutes of Health (NIH) Clinical Center's department of bioethics say that "off-label use has been identified as one aspect of problematic drug prescribing," in part because of inadequate data regarding drug safety and effectiveness for the off-label use.

An Issue for Doctors

Some doctors may also be confused about a drug's approval status. A surprising number of doctors think a medicine is FDA-approved for something when it is not, Alexander and colleagues recently reported in Pharmacoepidemiology and Drug Safety.

"This is not a trivial issue," Alexander says. "Our findings suggest that some off-label prescribing might be driven by mistaken beliefs about FDA approval and the level of evidence supporting off-label drug use."

Alexander says better strategies and tools are urgently needed to inform doctors about common, off-label uses that pose the greatest harm. Misunderstandings about a drug's approved use or side effects can increase the patient's risk of medication errors and dangerous outcomes.

For example, Alexander's research showed that nearly one in five doctors questioned who prescribed the drug quetiapine (Seroquel) for dementia with agitation mistakenly believed it was approved for such use. But the medicine carries a "black box" warning -- the FDA's sternest warning -- stating that the use of antipsychotic drugs was associated with an increased death risk in elderly patients with dementia.

Psychiatric medicines are among the most common drugs to be prescribed off-label, and their use in children is of special concern. Many drugs prescribed to children are used off-label because medications are less commonly tested in this age group. In March 2009, researchers reported in Academic Pediatrics that 62% of outpatient pediatric visits resulted in an off-label prescription. Children under age 6 were most likely to be prescribed a drug off-label.