What You Should Know About Off-Label Drug Use

Doctor in his office giving a medical prescription to the patient, healthcare concept

It may have happened to you: A doctor prescribes a drug without telling you much about it, and you pick it up at the pharmacy. Curious, you go online and discover the drug is approved and commonly used for another disease or condition, but there’s no mention of your condition.

It happens all the time, especially in cancer care. In fact, an estimated 1 in 5 prescriptions in the US are for so-called “off-label” uses.

The term refers to the drug approval process. The FDA approves drugs for specific purposes, based on detailed studies drug companies must submit to the agency. A drug’s formal label serves as a guide for doctors and pharmacists on its use, side effects and other specifics.

But, by law, the FDA cannot restrict that medicine to the use or uses for which it’s been approved. Once approved, doctors can prescribe it as they see fit.

The history of that policy is complex, but basically it’s because doctors’ trade organizations didn’t want the FDA to be able to dictate the practice of medicine. Congress went along. Regulate the approval of drugs: Yes. Tell doctors what to do: No.

Drug Companies and Off-Label Use

Is off-label use dangerous or risky? Should you ever take a prescription drug off-label?

Other research has linked off-label use to higher rates of side effects and adverse reactions. In a study published in JAMA Internal Medicine in January, the rate of side effects was 54% higher.

There’s a new and vigorous debate around off-label use. More precisely, the promotion by drug companies of off-label use. It started a few years ago and got kicked into high gear last year. At stake is whether drug companies get more leeway to actually promote off-label use to doctors.

In my view, that is dangerous and we should all be concerned. Here’s the short version of what’s afoot.

FDA rules prohibit drug companies from advertising and promoting off-label uses to doctors (or the public). But you could call the rules weak. Over the years, the companies have taken advantage of that weakness. They do so because of the potential profits. If they can build momentum behind an off-label use, they make more money. Sometimes lots more.

In fact, the potential rewards are so substantial that drug companies routinely test the limits of the laws and risk big penalties. Two numbers telegraph this point. Over the past 25 years, the federal government has collected around $15 billion in civil and criminal fines from pharmaceutical companies for off-label promotion. But experts estimate that sales of the drugs involved in those cases yielded pre-tax profits that are at least 10 times that amount — $150 billion.

Among the most recent cases, GlaxoSmithKline was fined $3 billion in 2012 for off-label promotion of several of its drugs, including the antidepressant Paxil (paroxetine). The company promoted Paxil for use in adolescents despite mounting evidence linking the drug to suicidal thoughts in that population and despite the FDA’s never having approved the drug for pediatric use.

Finding Ways Around Off-Label Rules

Despite such cases, several courts — including a federal appeals court in 2012 — have ruled in favor of drug companies’ right to communicate with doctors about the off-label use of the medicines they make.

The legal issues are dense, but the bottom line is that the courts have, to date, bought the companies’ argument that FDA’s current rules infringe their First Amendment “commercial speech” rights. The only stipulation the courts have made in 3 key cases so far is that the company’s communication to doctors involving off-label use must be “truthful and non-misleading,” and based on medical evidence even if nonconclusive.

The FDA has not appealed the decisions and claims that the decisions will not affect its enforcement of off-label “promotion” (versus “communication”). And the agency announced earlier in 2016 that it would issue revised guidance on off-label promotion and communication this year.

Meanwhile, to the consternation of consumer advocates, the FDA in March 2016 cut a deal with one company, Amarin Pharma, that allows it to promote an unapproved indication for its prescription omega-3 fish oil product (Vascepa) to reduce triglycerides in the blood.

Advice on Off-Label Drug Use

Doctors and researchers agree that some off-label uses are warranted. For example, a group of high blood pressure and heart disease medicines called beta-blockers are widely prescribed off-label for stage fright and performance anxiety. Since the drugs are available as generics, no drug company has sought approval for this use.

Cancer drugs are routinely prescribed off-label. Companies seek approval for one indication because conducting studies to prove a cancer drug may treat multiple cancers is very costly. But cancers spread and grow in similar ways and specialists look closely at a drug’s mechanism of action to see if it may work off-label. For some cancer drugs, a third to half of their use is off-label.

The problem is that the bulk of off-label use is not well grounded in science or backed by strong evidence. Indeed, much if it is sketchy. Studies have variously found between half and three-quarters of off-label use to have poor or no scientific support.

Do Your Homework

Most doctors (though not all, studies show) know when they are prescribing a drug off-label, but they don’t always tell patients. Neither do pharmacists. So, you have to ask — and always should — with every new prescription, especially if the drug is being prescribed in an inherently risky or high-stakes situation, such as cancer treatment.

Make it routine practice as well to check every drug you take online. The approved indications are easy to find. Try dailymed.nlm.nih.gov, search by drug, then click Indications & Usage.

What takes more digging, unfortunately, is finding out if an off-label use is widely accepted and backed by good evidence. Websites like drugs.com and WebMD often don’t have information about off-label use. You have to Google it. And, of course, circle back to your doctor or pharmacist if you don’t find the information you need.

If you are prescribed an expensive drug off-label, you are likely to hear about it from your pharmacist or health insurer. It may not be covered. That’s another reason to be proactive in getting the information up front from your doctor.

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