MONDAY, May 8, 2006 (HealthDay News) -- The "off-label" use of prescription medications -- for conditions other than those approved by the U.S. Food and Drug Administration -- occurs in about one in every five prescriptions filled in the United States, a new study finds.
Unfortunately, the practice is potentially risky, since three-quarters of these off-label uses lack solid scientific support, experts say.
"The science for off-use can range from very carefully done rigorous trials that are available in peer-reviewed literature but not submitted to the FDA, to anecdotal evidence with no real scientific basis," said Dr. Mark Fendrick, professor of internal medicine at the University of Michigan School of Medicine in Ann Arbor.
"Before we say off-label use is positive or negative, we need to understand the amount of evidence for [a] particular use," said Fendrick, who was not involved in the study.
"The FDA approves for specific indications. It doesn't vouch for the safety and efficacy of all uses," added Dr. Randall Stafford, senior author of the study and associate professor of medicine at the Stanford Prevention Research Center. "That means there are drugs that are used for things other than FDA indications. We don't necessarily know if this is a good thing or a bad thing, but we do know that drugs used for those off-label indications have clearly received less scrutiny."
One possible remedy might be better monitoring of off-label use after drugs make it to the marketplace.
This type of surveillance, Stafford said, "would be particularly important for off-label uses which haven't gone through that initial step of being reviewed by the FDA."
"Difficulties have arisen over the last decade with drugs being approved and then removed from the market. Those situations have largely involved using the drugs exactly as they're approved. Off-label is, in a sense, where we are going out on a limb," he said.
As it now stands, once a medicine is approved by the FDA and makes it to the marketplace, it can be prescribed for any condition. But while the practice is legal, it may not always be safe.
For example, the blood-clotting drug NovoSeven, approved in the United States to treat hemophilia, has been linked to strokes, heart attacks and deaths when used off-label to treat cerebral hemorrhages and other types of serious bleeding.
And the drug letrozole (brand name Femara) is often prescribed as a fertility aid, even though it is only approved to treat breast cancer in postmenopausal women. When prescribed off-label, it may cause birth defects and miscarriages.
But Fendrick noted that getting any additional FDA approval for a drug costs pharmaceutical companies lots of money.
"To get a claim in the FDA in the U.S., you need two randomized, controlled trials," Fendrick explained. "It's expensive to get a claim."
To determine how frequently and for what reasons off-label use occurs, the authors of this study analyzed data from a national survey of office-based physicians. The survey, conducted in 2001, looked at prescribing patterns for 160 commonly prescribed drugs.
That year, 725 million total prescriptions were written for this sample of drugs.
According to the survey results, there were an estimated 150 million off-label prescriptions written, representing 21 percent of total use.
Of those, 27 percent were for indications supported by scientific evidence, while the remaining 73 percent, or 109 million prescriptions, had little or no evidence supporting the use in question.
The most common off-label uses were for heart medications (46 percent), anticonvulsants (46 percent) and asthma medications (42 percent).
The highest proportion of off-label use among specific medications was for gabapentin (brand name Neurontin, an anti-seizure drug), for which 83 percent of prescriptions were off-label, and amitriptyline hydrochloride (brand name Elavil, an antidepressant), for which 81 percent of prescriptions were off-label.
Eighty percent of the off-label prescriptions for gabapentin had little or no scientific evidence to back them up, the study found. Gabapentin drew controversy when its manufacturer, Pfizer, was accused and convicted of inappropriate marketing of off-label uses. It is illegal for pharmaceutical companies to promote off-label usage of their products.
Psychiatry and allergy medications were most likely to be prescribed off-label with limited or no scientific basis (96 percent and 89 percent, respectively).
Among the drugs that did have support for off-label use were certain antibiotics and Albuterol, approved for asthma but used also for chronic obstructive pulmonary disease.
The bottom line, the authors stated, is that off-label usage needs to be more rigorously scrutinized. Physicians, too, need to be alert to the potential pros and cons.
"Since all medical interventions, including all drugs, come with a risk, it's important to inquire about the potential benefit before exposing an individual to potential adverse consequences and costs," Fendrick said.
More information
For more on off-label use of drugs, head to the U.S. FDA.
