31812017
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`Off-Label Drug Use
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`Off-label Drug Use
`What is off-label drug use?
`
`In the United States new drugs are tested in clinical trials (research studies) before they are approved by
`the US Food and Drug Administration (FDA) for use in the general public. The clinical trials are done to
`show that the drug:
`
`• Works to treat a certain medical condition
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`• Works the way it's expected to
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`•
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`Is safe when used as directed
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`When the FDA is satisfied that the drug works and is safe, it and the maker of the drug create the drug
`label. This is not an actual label that sticks to a bottle, but a report of very specific information about the
`drug. The FDA must approve this report, which is made available to all health profession a Is who prescribe
`or sell the drug.
`
`The drug label gives information about the drug, including the specific medical condition(s) it's approved
`for (called the indication(s) for use), the doses to be used, and how it's to be given. When a drug is used in a
`way that is different from that described in the FDA-approved drug label, it's said to be an "off-label" use.
`This can mean that the drug is:
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`• Used for a different disease or medical condition
`
`• Given in a different way (such as by a different route)
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`• Given in a different dose than in the approved label
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`For example, when a chemotherapy drug is approved for treating one type of cancer but is used to treat a
`different cancer, it's off-label use. The same is true if a drug is approved to treat a type of cancer at a
`specific stage (extent of spread), but it is used to treat a cancer at a different stage.
`
`Off-label is also called non-approved or unapproved use of a drug.
`
`Is off-label drug use legal?
`
`https:/lwww.cancer.orgltreatmentltreatments-and-side-effectsltreatment-types/chem alherapy/off-label-ctug-use.hbnl
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`MYLAN - EXHIBIT 1066
`Mylan Laboratories Limited v. Aventis Pharma S.A.
`IPR2016-00712
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`31812017
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`Off-Label Drug Use
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`The off-label use of FDA-approved drugs is not regulated, but it is legal in the United States and many
`other countries. An exception to this is the use of some controlled substances, such as opioids (pain
`medicines like morphine and fentanyl). These drugs cannot legally be prescribed in the United States
`except for approved purposes.
`
`While it's legal for doctors to use drugs off label, it's not legal for drug companies to market (advertise or
`promote) their drugs for off-label uses. Off-label marketing is very different from off-label use.
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`Why are drugs used off-label?
`
`Older, generic (non-brand name) medicines are the ones most often used off label. New uses for these
`drugs may have been found and there's often medical evidence from research studies to support the new
`use. But it's often too costly for the makers ofthe drugs to put them through the formal, lengthy, and
`expensive process required by the FDA to officially approve the drug for new uses.
`
`Off-label drug use is common in cancer treatment because:
`
`• Some cancer drugs are found to work against many different kinds oftumors.
`
`• Chemotherapy treatments often combine drugs. These combinations might include one or more
`drugs not approved forth at disease. Also, drug combinations change overtime as doctors study
`different ones to find out which work best.
`
`• Cancer treatment is always changing and improving.
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`• Oncologists (cancer doctors) and their patients are often faced with problems that have few approved
`treatment options. This is especially true for less common types of cancer.
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`• Oncologists and their patients may be more willing to try off-label drugs than other medical
`specialties.
`
`What problems can be caused by off(cid:173)
`label drug use?
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`Reimbursement
`
`The biggest problem is getting insurance plans to pay (reimburse) for off-label drug use. Many insurance
`companies will not pay for an expensive drug that's used in a way that's not listed in the approved drug
`label. They do this 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 insurance to cover medically appropriate cancer therapies. This law includes off-label uses if the
`treatment has been tested in careful research studies and written up in well-respected drug reference
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`31812017
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`Off-Label Drug Use
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`books or medical journals. In 2008, Medicare rules were changed to cover more off-label uses of cancer
`treatment drugs.
`
`Still, the health insurance coverage laws and regulations are complex. If your doctor is thinking about off(cid:173)
`label drug use, you and your doctor should carefully check your health plan's coverage. If you are denied
`coverage, it might help ifthe doctor sends the insurer copies of peer-reviewed journal articles or other
`respected sources that support the off-label use.
`
`Legal risk
`
`Another problem is that off-label drug use often does not reflect "standard of care" treatment. This could
`raise concerns about the legal risk to the health care provider should a patient have an unwanted or bad
`outcome from the treatment.
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`Lack of regulation and information
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`The FDA does not regulate the practice of medicine. In general, once the FDA approves a drug, licensed
`doctors can use it for any purpose they consider medically appropriate.
`
`One of the biggest problems related to widespread off-label use is the lack of information about how to
`best use the drug other than for what it was approved. The drug label is one ofthe most reliable and easy(cid:173)
`to-find sources of information available to health professionals, caregivers, and patients. But the label can
`only contain the information that's been approved by the FDA, and it does not cover 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. Some professional health organizations develop
`treatment guidelines that may offer options including off-label drug uses. Treatment guidelines are based
`on information from medical literature, including clinical trials, and recommend standard ways to treat
`certain diseases.
`
`Lack of information on off-label drug use and outcomes may also put patients at a higher risk for
`medication errors, side effects, and unwanted drug reactions. It's important that the patient and doctor
`talk about the possible risks of using the drug and weigh them against the possible benefits.
`
`How common is off-label drug use?
`
`Little information is available on off-label prescribing in oncology in the US. Off-label use can vary greatly
`from one doctor to another, depending on doctors' preferences, knowledge, and past patient experiences.
`A 2008 study found that 8 out of 10 cancer doctors surveyed had prescribed drugs off-label. Off-label drug
`use is also well-documented and very common in certain other settings, such as in pediatrics and HIV/AIDS
`care.
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`31812017
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`Off-Label Drug Use
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`Studies have reported that about half of the chemotherapy drugs used are 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."
`
`Actual off-label use might be even higher than what has been reported.
`
`What other types of drugs are used off
`label in cancer treatment?
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`Chemotherapy and other cancer treatment drugs (such as hormone therapy, immunotherapy, and
`targeted therapy drugs) can be used off label, but so can some other drugs used during the course of
`cancer treatment.
`
`Treating certain types of pain with tricyclic antidepressants is an example of off-label drug use. This old
`class of drugs is approved and labeled to be used for clinical depression. Today these drugs are seldom
`used to treat depression because safer drugs are available. But doctors have found that the tricyclics often
`work very well in treating certain types of pain.
`
`Another example is lorazepam (Ativan"l, an anti-anxiety drug that is often used as an anti-nausea drug in
`cancer treatment. In oncology, lorazepam is most commonly given under the tongue (the sublingual
`route), which is also not listed on the drug label. In this case, it's 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 might want to ask your doctor. Start by asking if all the drugs recommended
`for your cancer treatment are approved for the planned use. If any of the drugs are not, you can ask:
`
`•
`
`•
`
`Is there evidence to support the off-label use ofthis drug to treat my type of cancer?
`
`Is this off-label drug likely to work better than an approved drug?
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`• What are the risks and benefits of off-label treatment with this drug?
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`• Will my health insurance cover off-label treatment with this drug?
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`•
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`If my treatment involves a combination of drugs and one ofthe drugs is being used off label, will my
`health insurance cover it?
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`31S'2D17
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`Olf-Lsbel Drug Use
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`- .
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`The American Cancer Society medical and editorial content team
`
`Ucancer/acs-medical-content-and-news-staff.htmi)Ourteam is made up of doctors
`and masters-prepared nurses with deep knowledge of cancer care as well as
`journalists, editors, and translators with extensive experience in medical writing.
`
`Last Medical Review: March 17,2015 I Last Revised: March 17,2015
`
`American Cancer Society medical information is copyrighted material. For reprint requests,
`please contact permission request@cancer.org (mailto:permission req uest@cancer.org}.
`
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`31812017
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`Off-Label Drug Use
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`Understanding Your Diagnosis
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`Finding and Paying for Treatment
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`Treatments and Side Effects
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`Survivorship: During and After Treatment
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`Caregivers and Family
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`Children and Cancer
`
`End of Life Care
`
`Find Support Programs and Services in Your
`Area
`
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`31812017
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`Off-Label Drug Use
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