The middle-aged woman who came in for an appointment told me that another doctor had prescribed hydroxychloroquine (Plaquenil) to help her with symptoms of Raynaud’s disease. With this condition, exposure to cold causes blood vessels in the fingers and toes to spasm, leaving the digits feeling frigid and numb—and occasionally blue.

Plaquenil, used to decrease joint pain and swelling, is approved by the Food and Drug Administration for the treatment of lupus and rheumatoid arthritis. But my patient insisted that she had never been diagnosed with either condition.

It turns out she had an off-label prescription. FDA approval means evidence has shown that a drug is safe and effective for a specific disease or symptom.

But many doctors (myself included) sometimes prescribe a drug for another indication or different population or age group than those for which it’s FDA-approved.

Research published in 2006 suggests that 20 percent of prescriptions are off-label. And because the FDA is considering allowing drug companies to advertise drugs for unapproved uses, we may see more off-label prescribing in the near future. Here’s what you need to know to get safe and smart treatment.

Off-Label Pros and Cons

Off-label prescribing is perfectly legal, and there are some good reasons for its use. Doctors often turn to it to help patients who haven’t responded to drugs that are FDA-approved for their condition. Sometimes, as with Raynaud’s, there are no FDA-approved drugs.

Doctors may also be tempted to prescribe an off-label drug when features of two conditions are similar. I suspect that happened with my patient, because a small number of those with Raynaud’s are also diagnosed with lupus.

But off-label prescribing can have drawbacks. For example, research suggests it can increase the risk of some side effects, which is what happened to my patient. She had been experiencing itchiness, an occasional side effect of Plaquenil­, for three years. It was so severe that her skin was covered by cuts and scars from scratching.

5 Questions to Ask

To make sure you’re fully informed about the status of your medications, I suggest asking these five questions each time you get a new prescription:

Is this an off-label use? Doctors often neglect to tell patients when they’re recommending a drug off-label. In fact, 94 percent of Americans say they have never been told by a physician that their medication wasn’t approved by the FDA for their condition, according to an October 2016 survey from Consumer Reports. So you must ask.

You can also find out by going to Daily Med, which is part of the National Institutes of Health. Search for the drug you take, then click on “Indications and Usage” to see whether your condition is listed.

Where’s the evidence? If your doctor has prescribed a drug off-label, there may be a good reason. A professional medical society may have deemed it a safe and effective choice. Or solid scientific research may suggest it’s useful for your condition.

But off-label prescribing is supported by strong evidence only about 20 percent of the time, according to a 2016 JAMA Internal Medicine study. And patients receiving prescriptions for off-label indications that lacked strong evidence were 54 percent more likely to experience an adverse drug event.

What are the risks and side effects? You should ask this question about any new prescription you’re given, but it’s especially important for off-label medications because the potential risks are higher.

In the case of my patient, the side effect she experienced—itching—disappeared when she stopped taking Plaquenil. But some side effects can cause life-threatening or permanent damage.

Are there better options? If you’re uncomfortable with the answers to the preceding three questions, ask whether FDA-approved drugs are available for your condition.

And find out whether medication-free measures, such as physical therapy or talk therapy, might be an option. We’re now finding that nondrug treatments may be more effective for conditions such as back pain, depression, and insomnia.

Will insurance cover it? If you feel satisfied that an off-label use is appropriate, be sure to call your insurance company to make sure it will pay for the drug. Medicare Part D may require a rigorous prior authorization process or may not cover your off-label prescription at all. 

Editor's Note: This article originally appeared in the July 2017 issue of Consumer Reports on Health.