Off-label use is the practice of prescribing drugs for a purpose outside the scope of the drug's approved label, most often concerning the drug's indication. In the United States, the Food and Drug Administration (FDA) requires numerous clinical trials to prove a drug's safety and efficacy in treating a given disease or condition. If satisfied that the drug is safe and effective, the drug's manufacturer and the FDA agree on specific language describing dosage, route and other information to be included on the drug's label. More detail is included in the drug's package insert. However, once the FDA approves a drug for prescription use, they do not attempt to regulate the practice of medicine, and so the physician makes decisions based on her or his best judgment. It is entirely legal in the United States and in many other countries to use drugs off-label. Exceptions to this are certain controlled substances, such as opiates, which cannot be legally prescribed except for approved purposes (at least in the U.S.). In Australia, amphetamines are included in these drugs which cannot be prescribed off-label.
Some drugs are used more frequently off-label than for their original, FDA-approved indications. A 1991 study by the U.S. General Accounting Office found that one-third of all drug administrations to cancer patients were off label and more than half of cancer patients received at least one drug for an off-label indication. Frequently the standard of care for a particular type or stage of cancer involves the off-label use of one or more drugs. An example is the use of tricyclic antidepressants to treat neuropathic pain. This old class of antidepressants is now rarely used for clinical depression due to side effects, but the tricyclics are often effective for treating pain.
Off-label use and the law
In the United States, FDA regulations permit physicians to prescribe approved medications for other than their intended indications. Marketing information for the drug will list one or more indications, i.e., illnesses or medical conditions for which the drug has been shown to be both safe and effective. Pharmaceutical companies are not allowed to promote a drug for any other purpose without formal FDA approval.
However, once a drug has been approved for sale for one purpose, physicians are free to prescribe it for any other purpose that in their professional judgment is both safe and effective; they are not limited to its official, FDA-approved indications. This off-label prescribing is most commonly done with older, generic medications that have found new uses but have not had the formal (and often costly) applications and studies required by the FDA to formally approve the drug for these new indications. However, there is usually extensive medical literature to support the off-label use.
Access to pharmaceutical industry documents have revealed marketing strategies used to promote drugs for off-label use.  In 1993, the US Food and Drug Administration (FDA) approved gabapentin (Neurontin®, Pfizer) only for treatment of seizures. Pfizer subsidiary Warner-Lambert used activities not usually associated with sales promotion, including continuing medical education and research, to promote gabapentin, so that within 5 years the drug was being widely used for the off-label treatment of pain and psychiatric conditions. In 2004, Warner-Lambert admitted to charges that it violated FDA regulations by promoting the drug for pain, psychiatric conditions, migraine, and other unapproved uses.  
The United States federal government is aggressively pursuing criminal and civil cases against pharmaceutical companies and their employees for promoting off-label uses of prescription drugs. In 2004, Pfizer/Warner-Lambert paid $430 million to the federal government to settle a whistleblower case that alleged the company engaged in a scheme to promote the epilepsy drug, Neurontin, for off-label uses such as for patients with bipolar disorder and Lou Gehrig's disease.
The position of the British General Medical Council on off-label prescribing may be found here.
Off-label use of narcotics
While off-label administration of non-narcotic medications is generally tolerated by U.S. authorities, prescription of DEA scheduled narcotics for unapproved purposes is not. Medical license revocation, asset seizure, and incarceration are all common consequences borne by doctors in violation of the prohibition laws.
Off-label use in Veterinary Medicine
The veterinarian has a much smaller pharmacopea available than does the human practitioner. Therefore, drugs are more likely to be used "off label" - typically, this involves the use of a human medication in an animal, where there is no corresponding medication licenced for that species.
This problem is compounded in "exotic" species (such as reptiles and rodents) where there are very few, if any licenced medications.
In addition, (especially in Europe), equine veterinarians are forced to use a lot of drugs off label, as the horse is classified as a food-producing animal.
Examples of off-label use (and non-use)
- Botulin toxin is approved for the treatment of muscle spasms. Under the tradename Botox, it has become the basis of a popular cosmetic anti-wrinkle procedure, which is much more economically important than the approved use.
- Bevacizumab has been used against Age Related Macular Degeneration, but the evidence for its use is anecdotal.
- Carbamazepine, has been used as a mood stabilizer and is accepted treatment for bipolar disorder.
- Methotrexate (MTX), approved for the treatment of choriocarcinoma, is frequently used for the medical treatment of an unruptured ectopic pregnancy. There is no FDA-approved drug for this purpose and there is little incentive to sponsor an unpatented drug such as MTX for FDA-approval.
- The SSRI medication sertraline is approved as an anti-depressant. It is also commonly prescribed off-label to help men suffering from Premature ejaculation.
- Buprenorphine has been shown experimentally (1982-1995) to be effective against psychiatric problems. Since buprenorphine is an opioid (narcotic) not approved for psychological use, prescription for psychiatric problems is prohibited. Apparently exceptions to the prohibition were allowed for the various experiments.
- Stimulants such as Amphetamine (Adderall) and Methylphenidate (Ritalin) are indicated for childhood attention deficit disorder (ADD/ADHD), but are often prescribed to treat adults as well. Atomoxetine (Strattera), a non-stimulant norepinephrine reuptake inhibitor is currently the only drug (In the United States) indicated for adult ADD. In Australia dextroamphetamine is indicated for adult ADHD treatment. While Atomoxetine is also indicated for the treatment in Australia, it only has a minor percentage of the drugs prescribed for the condition, due to its prohibitively high price, as it is currently not subsidised by the Government's Pharmaceutical Benefits Scheme, whereas the stimulant medications methylphenidate and dextroamphetamine are.
- ↑ Michael A. Steinman, MD; Lisa A. Bero, PhD; Mary-Margaret Chren, MD; and C. Seth Landefeld, MD (2006). "Narrative Review: The Promotion of Gabapentin: An Analysis of Internal Industry Documents". Annals of Internal Medicine. 145 (4): 284–293. Retrieved 2006-08-14.
- ↑ Jane E. Henney, MD (2006). "Editorial: Safeguarding Patient Welfare: Who's In Charge?". Annals of Internal Medicine. 145 (4): 305–307. Retrieved 2006-08-14.
- ↑ US Department of Justice Press Release: WARNER-LAMBERT TO PAY $430 MILLION TO RESOLVE CRIMINAL & CIVIL HEALTH CARE LIABILITY RELATING TO OFF-LABEL PROMOTION Retrieved 14 August 2006
- ↑ For more information on liability and the law, follow the arrow to an article by False Claims Act lawyer Erika Kelton, titled "Sales tactics, whistleblowers and qui tam lawsuits in the pharmaceutical industry."
- 5. Kuntz, Richard M. "Off-Label Prescribing of Antidepressants and Anxiolytics: An Attorney's Guide to Psychoactive Drugs," 26 Journal of Psychiatry & Law 519 (1998)