You likely have heard of off-label prescription use. You may have even been prescribed a medication like this before. Off-label prescription drug use is legal and widely accepted in the United States and is more common than we think.
A report published by the U.S. Congressional Research Service shows a variation in off-label drug use dependent on factors like where the data originates.
A 2016 Canadian study that tracked prescriptions written in primary clinics estimated that 12% of those written by in-office physicians were for off-label drug use. According to the National Ambulatory Medical Survey, roughly 38% of prescriptions are typically written for off-label drug use.
Read on to learn about what off-label drug use is, why it occurs, and what to ask your doctor about it.
To help clarify what off-label use means, let’s start by explaining what
When the FDA approves a drug, it works with the manufacturer to create a label. This drug label includes the label on the drug package and a balanced, detailed report
This report includes key information, such as:
- the disease, symptom, or condition the drug is approved to treat, also called the drug indication
- the dosage for the drug, or how much and how often the drug should be taken
- the drug route and drug form, such as a tablet taken by mouth
- the age ranges of people the drug is authorized to treat
- the side effects the drug could cause
The package insert also
- details about boxed warnings
- strategies for
managingthe risks of using the drug, or risks evaluation and mitigation strategies (REMS)
- patient counseling information, which is
calleda medication guide
Doctors use the information to help them decide how to prescribe and monitor the use of the drug.
Off-label drug use means the drug is FDA approved for one purpose but
This lack of approval is not because the FDA refuses to provide it. Rather, it’s because the FDA has not been asked to evaluate the drug for that particular purpose.
That means the alternative use is not included in the drug label, and the FDA does not provide any guidance for the alternative usage of the drug.
However, your doctor can still use the drug for an alternative purpose. This is because the FDA regulates drug testing, approval, and marketing. But they do not oversee how doctors use drugs to treat their patients. So your doctor can prescribe a drug however they think is best for your care.
If your doctor decides to use a drug off-label, that means they’re prescribing it in one or more of the following ways:
- For a condition that has not been reviewed or approved by the FDA. For instance, aripiprazole (Abilify) is approved to treat schizophrenia, but doctors sometimes prescribe it off-label to treat dementia-related psychosis.
- In a dosage or by a route that has not been reviewed or approved by the FDA. For example, long-acting morphine tablets are not approved for rectal use. However, they are sometimes given that way to hospice patients who cannot swallow pills.
- In a patient population that has not been reviewed or approved by the FDA. Polyethylene glycol 3350 (Miralax) is not approved for use in children. But your child’s doctor may decide to prescribe it for your child.
Another example of a drug commonly prescribed for off-label use is dexamethasone (Decadron). It’s approved for many uses, such as treating allergic reactions and reducing inflammation or swelling. It’s not approved to treat lung inflammation caused by COVID-19 infection. Still, it’s been widely used off-label since 2020 for this purpose.
Some off-label uses work so well that they’re used as a first-line treatment. This means they’re the main treatment used for a condition.
One example is tricyclic antidepressants. These drugs
Additional examples of common off-label drug uses are:
|Drug names||FDA-approved use (indication)||Common off-label use|
|amitriptyline||depression||migraine headache pain, phantom-limb pain|
|carbamazepine (Tegretol, Tegretol XR, Epitol)||seizures, trigeminal neuralgia||bipolar disorder|
|clonidine (Kapvay)||high blood pressure||alcohol and opioid withdrawal symptoms, insomnia|
|cyclobenzaprine (Amrix, Fexmid)||muscle spasm||migraine headache pain, fibromyalgia|
|duloxetine||depression||stress urinary incontinence|
|fluoxetine||depression||social phobia, post-traumatic stress disorder (PTSD)|
|gabapentin (Neurontin)||seizures||diabetic nerve pain, restless leg syndrome|
|hydroxyzine pamoate (Vistaril)||itching||insomnia, seasonal allergies|
|lamotrigine (Lamictal, Lamictal XR, Lamictal CD, and Lamictal ODT)||seizures, bipolar disorder||fibromyalgia|
|lisinopril (Prinivil and Zestril)||high blood pressure||diabetic kidney protection|
|metformin (Glucophage, Glumetza, Fortamet, and others)||diabetes||polycystic ovary syndrome (PCOS), pregnancy, diabetes|
|metoprolol succinate (Toprol-XL)||high blood pressure||migraine headache prevention|
|prazosin (Minipress)||high blood pressure||nightmares, PTSD|
|propranolol||high blood pressure||anxiety|
|quetiapine||schizophrenia, bipolar disorder||insomnia, anxiety, dementia|
|semaglutide (Ozempic, Wegovy, Rybelsus)||diabetes||weight loss|
|tamsulosin (Flomax)||enlarged prostate in men||to relax the urinary tract in females with kidney stones|
Perhaps the main benefit of off-label drug use is that it gives you access to a broader range of drugs. Your doctor has more treatment options than if they only prescribe drugs for approved uses.
The increased drug access can benefit people with many conditions, from migraine to HIV. Specific reasons
- New uses. Doctors and researchers may have found a new use for an older drug called repurposing, but the drug maker
has not requestedFDA approval for that use.
- Lower cost. Drugs available for years longer than newer approved drugs may have generic forms available. Typically, if newer treatment costs exceed your budget, your doctor will try to find alternative drugs, including less expensive generic medications.
- Limited usage. A drug maker may not have requested FDA approval for the use of the drug in a certain patient group because many studies are still designed to first prove safety and efficacy in adult white males. Other people, such as females, children, People of Color, and people with disabilities, are often left without approved drugs because of this
- Lack of appropriate approved choices. This may be the case in several situations. For example, approved drug use may not work to treat your life threatening condition. Your doctor may think that off-label drug use offers a higher chance of benefit.
- Allergy to an approved drug for a specific condition. A doctor may prescribe a drug off-label if you experience an allergic reaction to or serious side effects from the approved drug for that indication.
Studies show that off-label prescription use is widespread in the United States, especially for pediatric healthcare,
For one 2018 review of studies, researchers reviewed off-label drug use in persons younger than 18 years old. In all except three studies, results showed that
In addition, a 2019 report published by the American Academy of Pediatrics on prescriptions in ambulatory care also found that between 2006 and 2015, 18.5% of prescriptions doctors wrote were for off-label use.
The study noted a rise in off-label prescription use in children. Doctors also prescribed more drugs off-label for use in females and people with certain complex or chronic conditions.
Another study from 2017 showed that off-label use is much more common in cancer care than in other types of medical care. The study found that
Because there are no FDA-approved instructions for prescribing drugs for off-label use, your doctor may research how best to use a drug off-label.
For instance, they may consult with other doctors who have used the drug. Or they may follow available
Also, some health organizations or professional societies may provide treatment guidelines for off-label use. Your doctor may follow any of these guidelines when prescribing a drug for off-label use.
Your doctor may prescribe a drug off-label that works so well and is so commonly used that it has become an accepted treatment method. As a result, your doctor may not see a reason to mention it.
According to the American Medical Association Journal of Ethics, your doctor is
In some cases, your doctor may believe it’s important to discuss the off-label use of a drug. For instance, if you have a rare cancer with only a few approved drug treatment options, your doctor may know of off-label drug use that could help you.
If there’s not much published research on that use, your doctor may want to talk with you about it. They may want you to know there could be unknown risks of using the drug for that purpose.
If a drug maker wants the FDA to approve a drug for new use, the maker must conduct new testing for that use. This testing can take years and be extremely costly, estimated to be approximately
Also, the FDA must thoroughly review all the testing results. In short, the drug approval process is lengthy and complex. Due to these hurdles, drug companies will not always pursue FDA approval of a drug for new uses.
If your doctor prescribes off-label drug use for you, take a moment to ask any questions you may have. You have a right to be involved in any decisions about your care.
Examples of questions you
- Is this drug approved to treat my condition?
- Why did you prescribe off-label use of this drug?
- Are there approved drugs available that can do the same thing?
- Does research support the use of this drug for this purpose?
- Will my health insurance cover this drug for off-label use?
- What side effects may I have from this drug?
- How will you monitor the off-label use of this drug in my medical condition?
- Have you ever given this drug for this off-label purpose? If so, what kind of results did your patients have?
What does “off-label prescribing” mean?
Is off-label drug use legal?
Off-label drug use is legal and common in the United States. The FDA is responsible for approving the use of a drug but does not have the authority to govern prescribing by doctors.
Many drugs are studied for purposes other than the original FDA-approved use and can be included in accepted treatment guidelines. Doctors may use those studies or guidelines to support the off-label medication use in your condition.
Does off-label drug use mean the doctor is experimenting on me?
Doctors are licensed by state boards of medicine and are responsible for providing ethical care to you. This means they must put your best interests first and do their best to give you care based on professional standards.
If the doctor is performing research, they must get your approval for this. If they are prescribing a drug-off label, they
Will I have more side effects using a drug off-label than using it for its approved use?
When using a drug off-label, you will need clear information on side effects to look for and how your doctor plans to evaluate the safety and efficacy of the drug in your condition.
How can I find information on off-label usage of the drug I have been prescribed?
Most doctors and pharmacists will have access to off-label drug use information in their prescribing and dispensing software. You may want to ask for printouts on off-label use.
Currently, there is no centralized consumer database for information on off-label drug use.
You can use the National Library of Medicine free drug database, DailyMed, to read about FDA-approved uses, side effects, and suggested safety monitoring.
What is the advantage of using a drug off-label?
A drug for off-label use may be used so frequently that many studies, treatment guidelines, and professional society discussions supporting their use in your condition may exist.
These types of resources
Also, using drugs off-label may give you more options to consider and a lower cost of therapy, especially in treating rare diseases and diseases with few approved treatments available.
Will my insurance pay for using a drug off-label?
Whether the insurance will pay for off-label drug use depends on many things, including:
- Is this a high cost drug?
- Does the drug have severe side effects?
- Are other approved drugs available?
- Is there a reason the doctor cannot prescribe an approved drug?
- Have you failed other approved therapies?
Most of the drugs commonly used off-label (see above table) are available in their less costly generic form, and insurance will most likely cover them. You can talk with your insurance provider, pharmacy, or doctor to get more coverage information.
High cost drugs may require an insurance process called prior authorization. This process will vary with different insurance companies.
Usually, the doctor must fill out paperwork and send it to the insurance company explaining why this particular off-label drug use is needed to treat your condition. Once the paperwork is complete, the insurance provider will determine whether the drug is covered. If approved, your insurance will cover the drug cost. If not, you will be responsible for covering the cost.
The most important thing to remember about off-label drug use is that doctors must use their professional judgment and seek your best interest when prescribing. That often could mean prescribing a drug for off-label use.
You, as a patient, may want to ask questions and do some research on your condition and the therapy your doctor is prescribing.
Ask other doctors or pharmacists on your healthcare team to help you when in doubt. They can suggest questions to ask and provide written information for you to read. Being well-informed will give you the confidence to make decisions that are right for you.