What Is Off-Label Drug Use?

The term "off-label drug use" sounds pretty serious, like it might be risky or illegal, but it's actually very common. Still, if you read about prescription drug lawsuits or scandals in the media, it can seem like off-label use always hurts patients or leads to litigation. So how can this type of prescription be both common in our healthcare system and legally problematic? The answer lies in the difference between the U.S. Food and Drug Administration's (FDA) prescription drug regulation and the practice of medicine by licensed physicians.

Off-Label Drug Use in a Nutshell

Off-Label Prescribing Off-Label Marketing
  • any prescription given for a use not approved by the FDA
  • committed by physicians and healthcare providers as a normal part of our healthcare system
  • 100% legal
  • really helpful for patients with rare conditions
  • possibly risky since side effects and adverse reactions may be unknown
  • regulated by state medical boards as part of the practice of medicine
  • promotion of any drug or medical device for a purpose not included on its FDA cleared label
  • committed by pharmaceutical and medical device manufacturers
  • illegal
  • a public health risk
  • unfair to patients and physicians
  • often punished with multi-billion dollar fines
  • regulated by the U.S. Food and Drug Administration

Any time your physician recommends a prescription for unapproved uses, be sure to ask questions. Will your health insurance or Medicare cover the drug as prescribed? Does your doctor know of any published scientific support for using the drug to treat your medical condition? What are the risks and benefits of using this drug? The key to keeping off-label prescriptions safe and accessible is simply clear communication between patient and physician.

Prescription Drug Approval

When a pharmaceutical company begins the prescription drug approval process, they have to tell the FDA what the drug treats. If the extensive scientific evidence in a clinical trial shows efficacy and safety, the target ailments become the drug's indications. You can find them listed under the Uses section in the package insert of an over-the-counter medication or on the full bag label of any prescription drug.

The FDA Does Not Regulate the Practice of Medicine

Once a drug gains approval for any indication, physicians can begin prescribing it for anything they deem appropriate. Yes, physicians are legally allowed to prescribe FDA approved drugs for anything they want, but why?

The drug approval process, mandated and overseen by the FDA, determines which products pharmaceutical companies can sell and how they can market those products. For example, in the past federal regulations prevented Bayer from marketing aspirin for the prevention of future heart attacks, because it did not have approval for that indication. They could market it for pain relief, because it went through the FDA clearance process, demonstrating safety and efficacy for relieving pain.

On the other hand, federal regulations had no bearing on whether or not a physician could instruct a patient to take aspirin for heart attack prevention. If medical journals publish scientific evidence indicating safe new uses of a drug, a physician can legally prescribe it for those uses.

FDA regulations allow physicians to exercise off-label prescribing discretion this way for several reasons:

  • Medical advances can and do occur more quickly than the FDA can approve or re-label medications.
  • Some patient populations like children or pregnant women are difficult to study for every drug.
  • Some indications may not have any viable treatment options.
  • The practice of medicine is controlled and monitored at the state level by medical licensing boards.

So healthcare providers in the United States have the freedom to prescribe any FDA approved medication they believe will help their specific patient. This allows them to make important, highly patient-specific treatment decisions using their medical expertise rather than depending on the drug approval process.

Risks and Benefits of On-Label vs. Off-Label Prescriptions

On-Label Drug Use Off-Label Drug Use
  • Drug safety and efficacy extensively studied
  • Predictable patient response rate
  • Established dosing protocols
  • Can provide treatment or relief for symptoms with no other treatment
  • Provides treatment access to patients often excluded from clinical approval studies
  • Can provide cutting edge treatment for scientifically studied indications not yet on the drug label
  • Clearly listed on the label
  • Risk of side effects may be unknown
  • May not be effective for the prescribed use
  • Dosing may be incorrect

Problematic Off-Label Drug Use

In most cases, off-label drug use provides more benefit than risk, but it does occasionally cause problems. In the past, large drug manufacturers have been fined by the Justice Department for intentionally marketing their drugs for off-label use, exposing patients and doctors to undue risk. Check out the examples below to see off-label marketing in the real world.

Zofran Off-Label Marketing

Zofran (ondansetron) was initially approved for the treatment of nausea and vomiting associated with chemotherapy regimens, but it quickly became the most popular prescription for morning sickness. Unfortunately, it had not been tested or approved for use in pregnant women, and some believe their children's birth defects were caused by the drug. In 2012, GlaxoSmithKline plead guilty to unlawfully promoting the drug for off-label use and paid $3 billion in fines, the largest settlement in U.S. history for fraudulent drug marketing.

Invokana Off-Label Promotion

Active ingredient canagliflozin was approved for the reduction of hemoglobin A1C levels in diabetic patients, but marketing efforts included unapproved uses. Advertisements for Invokana openly promoted blood pressure and weight reduction despite their absence from the label. These off-label uses may have contributed to the swift adoption of the drug in diabetic patients.

Manufacturer Janssen Pharmaceuticals currently faces over 1,100 lawsuits over side effects not mentioned on the original drug label. Those lawsuits are unrelated to Janssen's illegal marketing efforts. If you experienced the negative effects of Invokana, from off-label promotion or otherwise, you can hold the manufacturers responsible.

Risperdal Promotion for Unapproved Uses

This atypical antipsychotic received FDA approval for the treatment of schizophrenia in adults in 1994, but the drug manufacturer promoted it for a number of unapproved uses. Risperdal was marketed as a treatment for both young people and the elderly despite not having FDA approval in those patient populations. The illegal marketing campaigns involved a number of kickback schemes and questionable methods for targeting children.

Johnson and Johnson settled a False Claims Act lawsuit alleging fraudulent Risperdal marketing for close to $2.2 billion in 2012. The massive settlement is unrelated to the thousands of lawsuits filed by patients harmed by the drug after receiving it for an off-label indication. Unfortunately, studies associated off-label Risperdal use in young boys with the abnormal development of breast tissue. A significant portion of Risperdal lawsuits were filed as a result of this extreme side effect.

Off-Label Promotion Hurts Patients

When prescriptions deviate from the standard of care, or the manufacturer markets them illegally, patients can suffer extreme and costly consequences. If you or a loved one were injured by an off-label prescription, you should speak to an experienced lawyer today to find out if you qualify for compensation.

Authored by Katy Moncivais, Ph.D.Medical Editor
Photo of Katy Moncivais, Ph.D.
Katy Moncivais holds a Ph.D. in Biomedical Engineering from The University of Texas at Austin. She’s an experienced Regenerative Medicine Consultant with a demonstrated history of working in the hospital & healthcare industry. Skilled in adult stem cells, medical devices, biomechanics, bacterial and mammalian cell culture, and regenerative medicine, she provides guidance on an array of topics affecting consumers. In her role at ConsumerSafety.org, Dr. Moncivais works alongside the writing and research staff to help deliver fact-based news stories to consumers. Her unique professional history alongside her rigorous educational background allows her to contribute to a variety of consumer-focused topics with a fresh perspective. In addition, Dr. Moncivais reviews portions of medically driven content to ensure scientific accuracy.
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