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What is off-label drug use?
In the United States new drugs are tested in 3 phases of clinical trials (research studies) before they are approved for use in the general public. The clinical trials are done to prove that the drug effectively treats a certain medical condition, works the way it is supposed to, and is safe when used as directed. When the Food and Drug Administration (FDA) is satisfied that the drug is safe and effective, it works with the maker of the drug to create the drug label. This is not an actual label that sticks onto a container, but a report of very specific information. The FDA also must approve this report, which is made available to health professionals who dispense and prescribe the drug. The drug label contains information about the drug, including the approved doses and how it's to be given to treat the particular medical condition for which it was approved. When a drug is used off-label, it is most commonly given for a different disease or medical condition than described in the FDA-approved label. Or it may be given by a different route, or in a different dosage. For example, chemotherapy approved for one type of cancer treatment and used to treat a different cancer is a common practice in oncology. This is considered off-label use. Off-label is also called "non-approved" or "unapproved" use of the drug.
Is off-label drug use legal?
The off-label use of FDA-approved drugs is not regulated, but it is entirely legal in the United States as well as many other countries. An exception to this is the use of some controlled substances, such as opioids, which cannot be legally prescribed in the United States except for approved purposes.
Why are drugs used off-label?
Off-label prescribing is most often done with older, generic medications. New uses for these drugs may have been found and there is likely medical evidence to support the new use. But the makers of the drugs have not put them through the formal, lengthy, and often costly studies required by the FDA to officially approve the drug for these new uses.
Off-label drug use is very common in cancer treatment. There are many reasons for this:
- Some cancer drugs are found to be effective against many different kinds of tumors.
- Cancer chemotherapy often involves the use of combinations of drugs. These combinations might include one or more drugs not approved specifically for that disease. Also, drug combinations change over time as doctors try different combinations and find out which seem to produce the greatest benefit for patients.
- Cancer treatment is always changing and improving.
- Oncologists are regularly faced with few approved treatment options, especially if the first treatment didn't work.
- Oncologists and their patients may be more willing to try off-label drugs than other medical specialties.
What problems are caused by off-label drug use?
The biggest problem with off-label drug use is reimbursement. Many insurance companies will not pay for an expensive drug that is used in a manner not listed in the approved drug label, on the grounds that its use is “experimental” or “investigational.” In cancer treatment, these issues have been largely addressed through 1993 federal legislation that requires coverage of medically appropriate cancer therapies. This law includes off-label uses if the treatment has been tested in research studies and documented in authoritative drug reference books or the medical literature. Still, the health insurance coverage laws and regulations are complex. If you are considering off-label drug use, you and your doctor should carefully check your plan's coverage policy. If coverage is denied when first requested, it may be helpful for the doctor to provide the insurer with copies of peer-reviewed journal articles or other respected sources that support the proposed off-label use.
Another problem is that off-label drug use often does not reflect "standard of care" treatment. This leads to possible concern about the legal risk of prescribing off-label should a patient have an unwanted or bad outcome from treatment.
The FDA does not regulate the practice of medicine. This means that once the FDA approves a treatment, licensed physicians can prescribe it for any purpose they consider medically appropriate. Off-label use can vary greatly from one doctor to another, and depends on the doctor's preferences, knowledge, and past patient experiences.
One of the biggest problems related to widespread off-label prescribing is the lack of information about such drug use. One of the most reliable and easy-to-find sources of information available to health professionals, caregivers, and patients is the drug label. But by definition, the label can only contain the information that has been approved by the FDA and, therefore, does not mention off-label uses. The medical literature reports clinical trials, including those that are not part of the FDA approval process. This is the main source of off-label use information, but treatment guidelines may also offer options that include off-label use. Treatment guidelines are based on information from medical literature, including clinical trials, and explain recommended ways of treating a particular illness. Lack of information on off-label drug use and outcomes may put patients at a higher risk for medication errors and unwanted drug reactions.
How common is off-label drug use?
Some information is available on off-label prescribing in oncology. Two 1991 studies done in the United States found that up to one-half of all chemotherapy was used for an off-label condition. A 1997 study reported that 60% (probably an underestimate) of medical oncologists had prescribed a chemotherapy drug off-label.
Off-label drug use is well-documented and very common in certain settings, such as oncology, pediatrics, and HIV/AIDS care. Several studies have reported that about half of the chemotherapy used is given for conditions not listed on the FDA-approved drug label. In fact, the National Cancer Institute (NCI) has stated, "Frequently the standard of care for a particular type or stage of cancer involves the off-label use of one or more drugs.” The actual use is likely much higher because chemotherapy is only one aspect of cancer treatment. Studies that look at all the drugs used in cancer treatment, such as anti-nausea drugs and pain medicines, have yet to be done.
What is an example of off-label drug use?
An example of off-label drug use is prescribing tricyclic antidepressants to treat certain types of pain. This old class of antidepressants is approved and labeled to be used for clinical depression. Today these drugs are seldom used for depression because safer drugs are now available, but the tricyclics often work very well in treating certain types of pain.
Another example is lorazepam (Ativan®), an anti-anxiety drug often used as an anti-nausea drug in oncology. In the oncology setting it is most commonly given the sublingual route (under the tongue), which is also not listed on the drug label. In this case, it is being given for an off-label use and by an off-label route.
What questions should I ask my doctor about off-label drug use?
Here are some questions you may wish to ask if your doctor is considering off-label drug use as part of your cancer treatment.
- Is there evidence to support the off-label use of this drug to treat my type of cancer?
- Is the off-label use of this drug likely to be more effective that the use of an approved drug?
- What are the risks and benefits of off-label treatment with this drug?
- Will my health insurance cover off-label treatment with this drug?
- If my treatment involves a combination of drugs and one of the drugs is being used off label, will my health insurance cover it?
Additional Resources
More Information From Your American Cancer Society
We have selected some related information that may also be helpful to you. These materials may be viewed on our Web site or ordered from our toll-free number (1-800-ACS-2345).
National Organizations and Web Sites*
In addition to the American Cancer Society, other sources of patient information and support include:
National Cancer Institute
Telephone: 1-800-4-CANCER (1-800-422-6237)
Internet Address: www.cancer.gov
US Food and Drug Administration, Center for Drug Evaluation and Research
Telephone: 1-888-463-6332
Internet Address: www.fda.gov/cder/
*Inclusion on this list does not imply endorsement by the American Cancer Society.
The American Cancer Society is happy to address almost any cancer-related topic. If you have any more questions, please call us at 1-800-ACS-2345 at any time, 24 hours a day.
References
American Society of Clinical Oncology. Reimbursement for Cancer Treatment: Coverage of
Off-Label Drug Indications. J Clin Oncol. 2006;24:3206-3208.
Kocs D, Fendrick AM. Effect of Off-label Use of Oncology Drugs on Pharmaceutical Costs: The Rituximab Experience. The American Journal of Managed Care. 2003;9: 393-402.
Mortenson LE. The off-label debate: a threat to the future of cancer care. Cancer Invest.
1991;9:597–599.
National Cancer Institute. Understanding the Approval Process for New Cancer Treatments. Available at: http://www.cancer.gov/clinicaltrials/learning/approval-process-for-cancer- drugs/page5. Accessed January 23, 2007.
Poole SG, Dooley MJ. Off-label prescribing in oncology. Support Care Cancer. 2004;12:
302–305.
Thakkar S. Oncologists judge themselves the best judges of cancer treatments. J Natl Cancer Inst. 1997;89, 1188-1189.
United States General Accounting Office (1991) Off-label drugs, reimbursement policies
constrain physicians in their choice of cancer therapies (report GAO/PEMD-91-14).
Washington DC.
Revised: 03/13/2007
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