Of all prescriptions written for 160 common medications, about one out of every five were prescribed off-label, according to recent research. This means that the drugs were used in ways never approved by the FDA.

To learn more about this practice, we spoke with Douglas Melnick, MD, MPH, a preventive medicine physician who worked in the pharmaceutical industry…

  • What is an "off-label" prescription? FDA approval is granted for medications that have been shown in clinical trials to be both safe and effective for a particular medical condition. However, once a drug is approved no matter what it's approved for-doctors can prescribe it for any medical condition.
  • Why do doctors prescribe medications off-label? For obvious reasons, pregnant women-and, until recently, most children-have been excluded from most drug studies, so few drugs have undergone the kind of testing required by the FDA in these particular groups. Therefore, a pregnant woman with, say, migraines, has little choice but to take a migraine drug off-label.

Also, it's common to discover new uses for old medications. Rather than wait for a drug company to conduct FDA-required studies on a medication's effect on a condition for which it was not approved—a process that can take years, cost hundreds of millions of dollars and might never be done-doctors use the drugs right away.

  • Is this practice responsible? In some cases, it would be irresponsible not to prescribe drugs off-label. For example, aspirin was known to reduce heart attacks long before it was given FDA approval for this use. Waiting might have resulted in thousands of unnecessary deaths.
  • Are there dangers associated with using drugs off-label? Most drugs that are prescribed off-label haven't been tested for such use in large populations using double-blind, placebo-controlled studies. These studies, which are the "gold standard," can take years to complete, but they are the only way to prove that a drug is both effective and safe. Some drugs that haven't been exhaustively tested for off-label uses will invariably prove to be ineffective. Others may prove to be dangerous.

For example, in 1973 the FDA approved an appetite suppressant, fenfluramine, for short-term use. Doctors then began prescribing it for longer periods (an off-label use) in combination with a drug called phentermine. Approximately 100 cases of heart-valve disease were reported in patients taking the combination drug, commonly known as Fen-Phen, before it was removed from the market.

  • What role do the drug companies play? It's illegal for pharmaceutical companies to promote-through advertising, conversations with doctors or other means—off-label drug uses. However, the industry routinely engages in practices to heighten awareness of off-label use.

In some cases, a drug's off-label uses may be more lucrative than its indicated use. If a company anticipates this, it may seek FDA approval for a so-called "decoy indication."

Here's how it works: Suppose that a company develops an ulcer drug that also shows potential for cancer prevention. The company will conduct a relatively inexpensive ulcer study-because cancer studies tend to be much lengthier and expensive. When the company gets FDA approval for this drug as an ulcer treatment, it will quietly put out the word that the drug also may work for cancer.

By law, pharmaceutical sales representatives are not allowed to discuss off-label uses with doctors. There's a loophole, however, if the doctor asks first. For example, suppose a doctor learns at a dinner conference sponsored by a drug company that a new drug is being used off-label to lower blood pressure. He can ask the drug manufacturer for a packet of information that contains abstracts or articles about the medication's effectiveness in treating high blood pressure.

In addition, medical professionals (most commonly, pharmacists) who work as medical liaisons for pharmaceutical companies are allowed to discuss off-label drug use with physicians—but, again, only if the doctor first asks about off-label uses of the drug.

  • Do doctors play any other role in the promotion of off-label drugs? A pharmaceutical company may recruit an influential physician to spread the word about off-label drug uses. This often is done indirectly-by funding research, for example or more directly by providing speaking fees. The goal isn't necessarily to conduct high-level research, but to generate buzz. When word gets out that a drug may work for an off-label use—and is being used by an expert in the field-physicians around the country will be more likely to try it.
  • Should patients worry about off-label prescriptions? They should, at a minimum, be aware of the practice. Every patient treated with an off-label drug is essentially taking part in an informal study. Will the drug work? Are there serious side effects? These are questions that truly get answered only during the FDA's approval process. Off-label drug uses, by definition, are more uncertain.

I suggest that patients who take any medication ask their doctors the following questions…

  • Is this drug FDA-approved for my condition? If not, why are you prescribing it? Are there other drugs that do have FDA-approval?
  • Do you know how many patients have been treated off-label with this drug? For how many years has it been used off-label?

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