When the doctor pulls out the prescription pad, most Americans assume the medication has been approved by the US Food and Drug Administration (FDA) for this particular condition. But that may not be the case. The doctor may be prescribing it for what is called off-label use.

The FDA evaluates the safety and effectiveness of a drug for treating a specific condition. Once the drug receives approval, doctors can prescribe it for any condition or any patient, even when those are different from what the FDA approved.

What Is Off-label Use?

Off-label drug use means prescribing a drug for a condition for which it has not received FDA approval. The term also refers to drugs ordered for a different population group, such as children instead of adults, or at a different dose or duration than was determined by the FDA to have a favorable risk-benefit ratio.

"Consumers should be told when they are receiving a drug for off-label use and make an informed decision if they want to accept the risk," says pharmacist Larry Sasich, of the consumer watchdog group Public Citizen, in Washington, DC.

The Approval Process

Since 1938, every drug sold in the United States has received a safety review by the FDA. In 1962, the FDA also became responsible for ensuring a drug's effectiveness.

When seeking approval for a new drug, manufacturers submit results from a series of clinical studies, indicating a specific use for the drug in a specific group of people (such as women or people with diabetes). The agency only approves a drug to treat conditions specified in the research.

Although the FDA reviews the scientific data very carefully, some side effects will not show up until very large numbers of patients start taking the medication. This is far more people than could ever be studied prior to approval.

Supplemental Approvals

After a drug has been on the market for awhile and new uses become identified, the drug company can conduct scientific research to confirm the safety and effectiveness of the new use and apply for a supplemental approval.

But often long before this happens, doctors begin to experiment with the use of medications for other purposes that seem logical, often based on analogies to similar drugs. For example, if one antidepressant is approved as a treatment for obsessive-compulsive disorder, doctors may try other antidepressants for the same purposes, even if they haven’t been approved for that use. This type of informal use may or may not eventually lead to formal research.

This is an accepted practice. However, it has some significant problems. One of the most significant is that doctors may incorrectly come to believe that a drug is effective for a given condition. Only double-blind, placebo-controlled studies can distinguish between expectation and the power of suggestion, and specific benefits. Both physicians and patients may incorrectly attribute benefits to a drug simply out of enthusiasm. The net effect is that the patient is placed at risk for side effects without real chance for benefit.

Benefits Versus Risks

Sometimes off-label use is the best possible treatment for a patient. For instance, a chemotherapy drug approved to fight one type of cancer may be given to someone with a different cancer. Or a doctor might order an unapproved combination of drugs to treat someone with AIDS. In these life-threatening situations, waiting for the additional research is not in the patient's best interest, and the potential benefits outweigh the risks.

The Consequences of Off-label Use

While off-label prescribing is generally considered safe when done by competent physicians, it has also contributed to some well-publicized harms. For example, fenfluramine and dexfenfluramine, two popular and effective anti-obesity drugs, were withdrawn from the market after reports suggested that up to 30% of patients who took these drugs in combination with other medications developed life-threatening changes in their heart valves. While off-label prescribing was not the only issue, this illustrates how the FDA approval process does not guarantee protection from serious adverse events.

What's a Consumer to Do?

Here are some tips for the next time your doctor prescribes a medication:

  • Ask about risks and benefits. Ask your doctor if the drug has been approved for your condition and about the potential benefits and risks involved.
  • Talk to the pharmacist. Often patients don't feel comfortable asking questions about medicine at the doctor's office. Sasich recommends that these consumers ask the pharmacist to review the package insert with them before filling the prescription.
  • Do some research. Look up the drug in the Physicians' Desk Reference or look in our drug database. Check for three things: whether your condition is an approved use, what the proper dose is, and what the proper duration of use is. You should also check if there are any known interactions with drugs you regularly take.
  • Inquire about other options. If you're not comfortable with a drug that has not been approved by the FDA for your condition, tell your doctor. Ask why he or she thinks you need this particular drug and if there's a similar drug that has been approved that you can take.