What Does ‘Off-Label’ Use Mean for Medications?

When looking at your treatment options, your healthcare provider may decide to have you use a medication differently than how it is normally prescribed. This is referred to as “off-label” use, and your provider may determine that it is the best option in treating your condition.

This article will go over when off-label use is commonly recommended, what the risks of off-label use are, and some examples of medications often used off-label.

What does ‘off-label’ mean?

The term “off-label” or “unapproved use” is when an FDA-approved medication is used in a way that has not been approved by the FDA. Off-label prescribing is a legal practice, and it is actually more common than you may think. In fact, 1 out of every 5 prescriptions are written for an off-label use.

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Examples of off-label uses can include, but are not limited to:

• When a medication is used for a condition that it is not approved to treat

• When a medication is dosed differently than what has been approved

• Treating children with a medication that has been approved for use in adults only

Off-label uses may eventually get approved by the FDA. But before that happens, the pharmaceutical company needs to invest time and money into doing the research required for the new use to be approved. This may not always happen given the costs associated with approving every possible use of a medication.

Why do healthcare providers prescribe drugs off-label?

Once a medication is approved by the FDA, healthcare providers can use their clinical judgement to prescribe it in ways that are medically appropriate for their patients. While an off-label use may not be the first choice to treat a condition, providers may use it as an alternative if there aren’t other effective options available. 

Here are a few common examples of when off-label prescribing is more frequently used.

Children

Off-label use is very common in children since most medications are approved only for use in adults and may not have been studied in younger populations. Examples of medications that are frequently prescribed off-label for children include drugs that treat gastrointestinal (GI) conditions, as well as antidepressants, antibiotics, and respiratory treatments.

Cancer

Cancer is another condition where off-label use is common. This is because many drugs used to treat cancer can work against more than one type of cancer. If you are receiving cancer treatment, you may be receiving a combination of medications. These combinations may not be approved by the FDA to be used together, but they can be effective in treating different types of cancer.

Diseases without approved treatments (e.g., COVID-19)

As the COVID-19 pandemic started to spread across the globe, providers were racing to find treatments that would work against the virus and manage its effects in critically ill patients. Some of these treatments included medications used to treat malaria and rheumatoid arthritis, as well as antiviral medications, antibiotics, corticosteroids, and other medications approved for other uses. 

Over the course of the pandemic, several of these medications have been studied off-label to identify which therapies may be effective in fighting the disease. Several treatments have been authorized for emergency use during the pandemic, and the FDA has approved at least one.

What are the risks of off-label use, and is it safe?

If you are prescribed a medication, you may not always know if it has been approved for the way you are taking it. And while it may be a good option to treat your condition, it doesn’t always come without potential risks. 

The purpose of the FDA approval process is to make sure that a medication has been shown to be safe and effective to treat the condition. Each approved medication comes with labeling that explains how the medication is used, any known risks and side effects, and other important information, such as how to detect and manage the risks. 

When a medication is used off-label, this means that its safety and efficacy has not been reviewed by the FDA. In this case, the benefits and risks may not be known for how you are using the medication. The risks of off-label use may overlap with some of the risks of approved uses, but we may not have a full picture of what can happen when you take it differently.

But even though off-label use can have risks, it is common practice and has a place in therapy when used appropriately. 

What does the FDA say about off-label use?

The FDA regulates the approval of medications, not the practice of medicine. This means that providers can use approved medications in ways that are best for their patients, even if it is outside of the approved labeling. But the FDA may step in if off-label prescribing is being done for research purposes. 

While many off-label uses are well documented and widely used, others may have little to no scientific support. The FDA advises that when prescribing a medication off-label, providers need to be well informed about the medication and make sure that the off-label use has scientific support. 

But there are restrictions in place when it comes to pharmaceutical companies. If these companies are found to be marketing uses of medications outside of the approved labeling, they may be subject to massive penalties.

Does insurance pay for off-label use?

Whether or not your insurance will pay for off-label use can be complicated. In general, you may have a harder time getting your plan to pay for a medication that has not been FDA-approved to treat your condition. 

But off-label use may be necessary for some people. In this case, insurers may use different tools to guide and manage coverage decisions for off-label use, including but not limited to:

• Prior authorization to make sure that you’ve tried other FDA-approved options, and that the medication is being prescribed appropriately

• Medically accepted indications from drug compendia, which are summaries of drug information reviewed and compiled by experts that can include both FDA-approved and off-label uses of drugs

Medically accepted indications are uses either approved by the FDA or supported by a drug compendium. A drug compendium may provide a recommendation, efficacy, and evidence rating for an off-label use. For example, the experts may recommend an off-label use based on a review of multiple, high-quality clinical trials involving large numbers of people. On the other hand, the experts may not recommend an off-label use because the available evidence is only expert opinion or case reports.

These ratings are often used by insurers like Medicare when deciding whether or not to cover an off-label use of a medication. 

What are some popular medications with off-label use?

Off-label use extends beyond pediatrics and cancer treatments, and it can include popular medications that are normally used to treat conditions like pain, seizures, diabetes, and depression. 

Here is a list of popular medications that are used off-label.

Gabapentin

Gabapentin (Neurontin) is a medication that was originally developed to treat seizures. Since then, it has also been approved to treat nerve pain that occurs after shingles. However, it is frequently used off-label for a growing list of conditions, including:

• Bipolar disorder

• Diabetic nerve pain

• Complex regional pain syndrome (chronic pain in the arm or leg after injury, surgery, etc.)

• Attention deficit hyperactivity disorder (ADHD)

• Restless leg syndrome

• Trigeminal neuralgia (a type of chronic facial pain)

• Migraine

• Drug and alcohol withdrawal seizures

Metformin

Metformin (Glucophage) is a medication approved to treat type 2 diabetes by helping to control blood sugar levels. One of the side effects is that it can lower your appetite, so it has gained popularity for off-label use in helping people lose weight. 

Naltrexone

Naltrexone (Revia) is a medication approved to treat opioid and alcohol dependence. But it is sometimes used off-label to treat impulse-control disorders like gambling. It is also used in lower doses, called low-dose or ultra-low-dose naltrexone, for conditions like fibromyalgia, multiple sclerosis, and cancer.

Topiramate

Topiramate (Topamax) is a medication approved to treat certain types of seizures and to prevent migraines. It also has a growing list of off-label uses, including:

• Nerve pain

• Alcohol dependency

• Eating disorders

• Bipolar disorder

• Obsessive-compulsive disorder (OCD)

• Posttraumatic stress disorder (PTSD)

• Tourette syndrome

Topiramate may also cause weight loss, and it has been used off-label to treat obesity. In 2012, it was approved for the treatment of obesity in combination with the drug phentermine under the brand name Qsymia.

Bupropion

Bupropion (Wellbutrin) is an antidepressant medication available as a few different versions, and it can be used to treat depression, seasonal affective disorder, and smoking cessation. Off-label uses include:

• Sexual dysfunction caused by antidepressants

• Attention deficit hyperactivity disorder (ADHD) in adults and children

• Depression associated with bipolar disorder

• Obesity

In 2012, the pharmaceutical company GlaxoSmithKline was charged a $3 billion fine for marketing off-label uses for bupropion like sexual dysfunction and weight loss. But in 2014, it was approved for weight loss in combination with the drug naltrexone under the brand name Contrave.

Acyclovir

Acyclovir (Zovirax) is an antiviral medication used to treat shingles, genital herpes, and chickenpox. It is sometimes used off-label in combination with a steroid to treat Bell’s palsy, and to treat inflammation of the esophagus caused by the herpes simplex virus (HSV).

Aimovig

Aimovig (Erenumab) is a newer medication used to prevent migraines in adults. But some providers use it off-label to help prevent other types of headache, including cluster headache and vestibular migraine (migraine with dizziness and vertigo). Emgality, a medication in the same drug class as Aimovig, has been approved to treat episodic cluster headache.

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Written by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

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