Off-label use
Encyclopedia
Off-label use is the practice of prescribing pharmaceuticals
for an unapproved indication
or in an unapproved age group, unapproved dose or unapproved form of administration. In the United States
, the Food and Drug Administration Center for Drug Evaluation and Research
(CDER) reviews a company's New Drug Application
(NDA) for data from clinical trials to see if the results support the drug for a specific use or indication. If satisfied that the drug is safe and effective, the drug's manufacturer and the FDA agree on specific language describing dosage, route of administration, and other information to be included on the drug's label. More detail is included in the drug's package insert.
The FDA approves a drug for prescription use, and will continue to regulate the pharmaceutical industry through the work of the Division for Drug Marketing, Advertisement and Communication (DDMAC). The FDA does not have the legal authority to regulate the practice of the medicine, and the physician
may prescribe a drug off label. Contrary to popular notion, it is legal in the United States and in many other countries to use drugs off label, including controlled substances such as opiates. Actiq
, for example, is commonly prescribed off label even though it is a Schedule II controlled substance. While it would be legal for a physician to independently decide to prescribe a drug such as Actiq off-label, it is illegal for the company to promote off-label uses to prescribers. In fact, Cephalon, the maker of Actiq, was fined for illegal promotion of the drug in September 2008. Under the Food, Drug, and Cosmetic Act (FDAC) at U.S.C. 21 §§301-97, manufacturers are prohibited from directly marketing a drug for a use other than the FDA approved indication. The Food and Drug Administration Modernization Act of 1997 created an exception to the prohibition of off-label marketing. Manufacturers are now able to provide medical practitioners with off-label information in response to an unsolicited request.
Among use of antipsychotic medications in the United States, a shift occurred from typical agents in 1995 (84% of all antipsychotic visits) to atypical agents by 2008 (93%). Atypical use has grown far beyond substitution for the now infrequently used typical agents. New drugs are often not tested for safety and efficacy specifically in children and even when they are tested, the results of these trials may not be disseminated to practicing physicians. A 2009 study found that 62% of U.S. pediatric office visits included off-label prescribing, with younger children at higher risk of receiving off-label prescriptions. Specialist physicians also prescribed off-label more frequently than general pediatricians.
A study published in 2006 found that off-label use was the most common in cardiac medications and anticonvulsants. This study also found that 73% of off-label use had little or no scientific support
By default use of non-approved drugs is common in obstetrics as, by 2010, during almost five decades of activity the FDA had approved only two drugs for obstetrical indications, namely oxytocin
and cervidil. A small market and the high risk of medicolegal action, as exemplified by the Bendectin
case, may explain the reluctance to develop drugs for approval.
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. A 1997 survey of 200 cancer doctors by the American Enterprise Institute and the American Cancer Society
found that 60% of them prescribed drugs off label. In some cases, patients may perceive the efficacy of treatments for off-label purposes to be higher than for their indicated purpose. 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 antidepressant
s to treat neuropathic pain
. This old class of antidepressant
s is now rarely used for clinical depression
due to side effects
, but the tricyclics are often effective for treating pain.
s and other healthcare practitioners to prescribe approved medications for other than their approved indications. Pharmaceutical companies are not allowed to promote a drug for any other purpose without formal FDA approval. Marketing information for the drug will list one or more indications, that is, illness
es or medical conditions for which the drug has been shown to be both safe and effective.
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, and are not limited to 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.
In 1993, the US FDA approved gabapentin
, marketed by Pfizer
under the name "Neurontin", 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 company paid $430 million to the federal government to settle the case.
Access to pharmaceutical industry documents have revealed marketing
strategies used to promote drugs for off-label use. 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. Between 2003 and 2008, U.S. federal prosecutors and state attorneys general brought more than a dozen cases against drug makers for off-label marketing and won more than $6 billion in criminal and civil settlements. In September 2009, Pfizer
paid $1.3 billion, the largest criminal fine ever imposed in the United States, for the off-label marketing of Bextra and three other drugs. Pfizer paid an additional $1 billion in civil penalties resulting from the same illegal activities.
has a much smaller pharmacopeia 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 many drugs off-label, as the horse is classified as a "food-producing animal" and many veterinary drugs are labeled specifically not for use in animals intended for human consumption.
This practice is permitted by the Animal Medicinal Drug Use Clarification Act of 1994 (P.L. 103-396). FDA specifically prohibits extralabel use of a number of antibiotics, anti-inflammatory drugs and hormones in food producing animals. FDA also tightly controls the use of certain veterinary-prescribed drugs when administered in the feed of food-producing animals.
Largent EA, Miller FG, Pearson SD. "Going Off-label Without Venturing Off-Course: Evidence and Ethical Off-label Prescribing." Arch Intern Med. 2009;169:1745-1747.
Mortenson LE. "The off-label debate: a threat to the future of cancer care." Cancer Invest. 1991;9:597-599.
Prescription drug
A prescription medication is a licensed medicine that is regulated by legislation to require a medical prescription before it can be obtained. The term is used to distinguish it from over-the-counter drugs which can be obtained without a prescription...
for an unapproved indication
Indication (medicine)
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. The opposite of indication is contraindication.-Drugs:...
or in an unapproved age group, unapproved dose or unapproved form of administration. In the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, the Food and Drug Administration Center for Drug Evaluation and Research
Center for Drug Evaluation and Research
The Center for Drug Evaluation and Research is a division of the U.S. Food and Drug Administration that monitors most drugs as defined in the Food, Drug, and Cosmetic Act. Some biological products are also legally considered drugs, but they are covered by the Center for Biologics Evaluation and...
(CDER) reviews a company's New Drug Application
New drug application
The New Drug Application is the vehicle in the United States through which drug sponsors formally propose that the Food and Drug Administration approve a new pharmaceutical for sale and marketing...
(NDA) for data from clinical trials to see if the results support the drug for a specific use or indication. If satisfied that the drug is safe and effective, the drug's manufacturer and the FDA agree on specific language describing dosage, route of administration, and other information to be included on the drug's label. More detail is included in the drug's package insert.
The FDA approves a drug for prescription use, and will continue to regulate the pharmaceutical industry through the work of the Division for Drug Marketing, Advertisement and Communication (DDMAC). The FDA does not have the legal authority to regulate the practice of the medicine, and the physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
may prescribe a drug off label. Contrary to popular notion, it is legal in the United States and in many other countries to use drugs off label, including controlled substances such as opiates. Actiq
Actiq
Actiq by Cephalon, is a solid formulation of fentanyl citrate on a plastic stick that dissolves slowly in the mouth for absorption across the buccal mucosa. Generically Actiq is a form of oral transmucosal fentanyl citrate . In the UK, Fentanyl is a Class A drug under the Misuse of Drugs Act 1971....
, for example, is commonly prescribed off label even though it is a Schedule II controlled substance. While it would be legal for a physician to independently decide to prescribe a drug such as Actiq off-label, it is illegal for the company to promote off-label uses to prescribers. In fact, Cephalon, the maker of Actiq, was fined for illegal promotion of the drug in September 2008. Under the Food, Drug, and Cosmetic Act (FDAC) at U.S.C. 21 §§301-97, manufacturers are prohibited from directly marketing a drug for a use other than the FDA approved indication. The Food and Drug Administration Modernization Act of 1997 created an exception to the prohibition of off-label marketing. Manufacturers are now able to provide medical practitioners with off-label information in response to an unsolicited request.
Frequency of off-label use
Off-label use of medications is very common. Generic drugs generally have no sponsor as their indications and use expands, and incentives are limited to initiate new clinical trials to generate additional data for approval agencies to expand indications of proprietary drugs. Up to one-fifth of all drugs are prescribed off label and amongst psychiatric drugs, off-label use rises to 31 %.Among use of antipsychotic medications in the United States, a shift occurred from typical agents in 1995 (84% of all antipsychotic visits) to atypical agents by 2008 (93%). Atypical use has grown far beyond substitution for the now infrequently used typical agents. New drugs are often not tested for safety and efficacy specifically in children and even when they are tested, the results of these trials may not be disseminated to practicing physicians. A 2009 study found that 62% of U.S. pediatric office visits included off-label prescribing, with younger children at higher risk of receiving off-label prescriptions. Specialist physicians also prescribed off-label more frequently than general pediatricians.
A study published in 2006 found that off-label use was the most common in cardiac medications and anticonvulsants. This study also found that 73% of off-label use had little or no scientific support
By default use of non-approved drugs is common in obstetrics as, by 2010, during almost five decades of activity the FDA had approved only two drugs for obstetrical indications, namely oxytocin
Oxytocin
Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
and cervidil. A small market and the high risk of medicolegal action, as exemplified by the Bendectin
Bendectin
Bendectin is a combination of pyridoxine and doxylamine prescribed to treat nausea and vomiting of pregnancy or morning sickness.-History:...
case, may explain the reluctance to develop drugs for approval.
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
Government Accountability Office
The Government Accountability Office is the audit, evaluation, and investigative arm of the United States Congress. It is located in the legislative branch of the United States government.-History:...
found that one-third of all drug administrations to cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
patients were off label, and more than half of cancer patients received at least one drug for an off-label indication. A 1997 survey of 200 cancer doctors by the American Enterprise Institute and the American Cancer Society
American Cancer Society
The American Cancer Society is the "nationwide community-based voluntary health organization" dedicated, in their own words, "to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and...
found that 60% of them prescribed drugs off label. In some cases, patients may perceive the efficacy of treatments for off-label purposes to be higher than for their indicated purpose. 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 antidepressant
Tricyclic antidepressant
Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
s to treat neuropathic pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
. This old class of antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
s is now rarely used for clinical depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
due to side effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
, but the tricyclics are often effective for treating pain.
United States
In the United States, FDA regulations permit physicianPhysician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
s and other healthcare practitioners to prescribe approved medications for other than their approved indications. Pharmaceutical companies are not allowed to promote a drug for any other purpose without formal FDA approval. Marketing information for the drug will list one or more indications, that is, illness
Illness
Illness is a state of poor health. Illness is sometimes considered another word for disease. Others maintain that fine distinctions exist...
es or medical conditions for which the drug has been shown to be both safe and effective.
However, once a drug has been approved for sale for one purpose, physicians are free to prescribe
Medical prescription
A prescription is a health-care program implemented by a physician or other medical practitioner in the form of instructions that govern the plan of care for an individual patient. Prescriptions may include orders to be performed by a patient, caretaker, nurse, pharmacist or other therapist....
it for any other purpose that in their professional judgment is both safe and effective, and are not limited to 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.
In 1993, the US FDA approved gabapentin
Gabapentin
Gabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...
, marketed by Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
under the name "Neurontin", only for treatment of seizures. Pfizer subsidiary Warner-Lambert used activities not usually associated with sales promotion, including continuing medical education
Continuing medical education
Continuing medical education refers to a specific form of continuing education that helps those in the medical field maintain competence and learn about new and developing areas of their field. These activities may take place as live events, written publications, online programs, audio, video, or...
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 company paid $430 million to the federal government to settle the case.
Access to pharmaceutical industry documents have revealed marketing
Pharmaceutical marketing
Pharmaceutical marketing , sometimes called medico-marketing, is the business of advertising or otherwise promoting the sale of pharmaceuticals or drugs. There is some evidence that marketing practices can negatively affect both patients and the health care profession...
strategies used to promote drugs for off-label use. 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. Between 2003 and 2008, U.S. federal prosecutors and state attorneys general brought more than a dozen cases against drug makers for off-label marketing and won more than $6 billion in criminal and civil settlements. In September 2009, Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
paid $1.3 billion, the largest criminal fine ever imposed in the United States, for the off-label marketing of Bextra and three other drugs. Pfizer paid an additional $1 billion in civil penalties resulting from the same illegal activities.
United Kingdom
Physicians in the United Kingdom can prescribe medications off-label. According to the British General Medical Council, off-label prescriptions must better serve patient needs than alternatives and must be supported by evidence or experience to demonstrate safety and efficacy.Examples of off-label use (and non-use)
- ActiqActiqActiq by Cephalon, is a solid formulation of fentanyl citrate on a plastic stick that dissolves slowly in the mouth for absorption across the buccal mucosa. Generically Actiq is a form of oral transmucosal fentanyl citrate . In the UK, Fentanyl is a Class A drug under the Misuse of Drugs Act 1971....
(oral transmucosal fentanyl citrate), a Schedule II controlled substance, is used off-label to treat moderate to severe chronic, non-malignant pain even though it is FDA-approved solely for breakthrough pain in cancer patients. - BevacizumabBevacizumabBevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....
(Avastin) has been used against wet age-related macular degenerationMacular degenerationAge-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...
, as well as macular edemaMacular edemaMacular edema occurs when fluid and protein deposits collect on or under the macula of the eye and causes it to thicken and swell. The swelling may distort a person's central vision, as the macula is near the center of the retina at the back of the eyeball...
from diseases such as diabetic retinopathyDiabetic retinopathyDiabetic retinopathy is retinopathy caused by complications of diabetes mellitus, which can eventually lead to blindness....
and central retinal vein occlusionCentral retinal vein occlusionThe central retinal vein is the venous equivalent of the central retinal artery, and like that blood vessel can suffer from occlusion , similar to that seen in ocular ischemic syndrome...
. - Buprenorphine has been shown experimentally (1982–1995) to be effective against severe, refractory depression.
- BupropionBupropionBupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
, when sold under the brand name Wellbutrin is indicated for depression. However, it is also sold under the name Zyban as a smoking cessation drug. In Ontario, Canada, smoking cessation drugs are not covered by provincial drug plans. Thus, a physician can write a prescription for Wellbutrin to assist with giving up the habit of smoking. - CarbamazepineCarbamazepineCarbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
, or Tegretol, has been used as a mood stabilizerMood stabilizerA mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, typically bipolar disorder.-Uses:...
and is accepted treatment for bipolar disorderBipolar disorderBipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
. - DexamethasoneDexamethasoneDexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...
and BetamethasoneBetamethasoneBetamethasone is a potent glucocorticoid steroid with anti-inflammatory and immunosuppressive properties. Unlike other drugs with these effects, betamethasone does not cause water retention. It is applied as a topical cream, ointment, foam, lotion or gel to treat itching...
in premature labor, to enhance pulmonary maturation of the fetus. - DoxepinDoxepinDoxepin is a psychotropic agent with tricyclic antidepressant and anxiolytic properties, known under many brand-names such as Aponal, the original preparation by Boehringer-Mannheim, now part of the Roche group; Adapine, Doxal , Deptran, Sinquan and Sinequan...
, has been used to treat Angiodema and severe allergic reactions due to its strong anti histamine properties. - GabapentinGabapentinGabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...
, approved for treatment of seizures and postherpetic neuralgiaPostherpetic neuralgiaPostherpetic neuralgia is a neuralgia caused by the varicella zoster virus. Typically, the neuralgia is confined to a dermatomic area of the skin and follows an outbreak of herpes zoster in that same dermatomic area...
in adults, is used off-label for a variety of conditions including bipolar disorderBipolar disorderBipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
, essential tremorEssential tremorEssential tremor is a slowly progressive neurological disorder whose most recognizable feature is a tremor of the arms that is apparent during voluntary movements such as eating and writing...
, hot flashes, migraineMigraineMigraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
prophylaxis, neuropathic painNeuropathic painNeuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...
syndromes, phantom limbPhantom limbA phantom limb is the sensation that an amputated or missing limb is still attached to the body and is moving appropriately with other body parts. 2 out of 3 combat veterans report this feeling. Approximately 60 to 80% of individuals with an amputation experience phantom sensations in their...
syndrome, and restless leg syndrome. - Magnesium sulfateMagnesium sulfateMagnesium sulfate is a chemical compound containing magnesium, sulfur and oxygen, with the formula MgSO4. It is often encountered as the heptahydrate epsomite , commonly called Epsom salt, from the town of Epsom in Surrey, England, where the salt was distilled from the springs that arise where the...
in obstetrics for premature labor and preeclampsia. - MethotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
(MTX), approved for the treatment of choriocarcinomaChoriocarcinomaChoriocarcinoma is a malignant, trophoblastic and aggressive cancer, usually of the placenta. It is characterized by early hematogenous spread to the lungs...
, is frequently used for the medical treatment of an unruptured ectopic pregnancyEctopic pregnancyAn ectopic pregnancy, or eccysis , is a complication of pregnancy in which the embryo implants outside the uterine cavity. With rare exceptions, ectopic pregnancies are not viable. Furthermore, they are dangerous for the parent, since internal haemorrhage is a life threatening complication...
. 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 sertralineSertralineSertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in...
is approved as an anti-depressant. It is also commonly prescribed off-label to help men suffering from premature ejaculationPremature ejaculationPremature ejaculation is a condition in which a man ejaculates earlier than he or his partner would like him to. Premature ejaculation is also known as rapid ejaculation, rapid climax, premature climax, or early ejaculation....
. - Stimulants such as AmphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
(AdderallAdderallAdderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...
) and MethylphenidateMethylphenidateMethylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(Ritalin) are indicated for childhood attention deficit disorder Benzphetamine (Didrex)(ADD/ADHD), but are often prescribed to treat this condition in adults, as well. Atomoxetine (Strattera), a non-stimulant norepinephrineNorepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
reuptakeReuptakeReuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
inhibitorEnzyme inhibitorAn enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
is currently the only drug (In the United States) indicated for adult ADDAdult attention-deficit disorderAdult attention deficit hyperactivity disorder is the common term used to describe the neuropsychiatric condition attention-deficit hyperactivity disorder when it is present in adults. Up to 60% of children diagnosed with ADHD in early childhood continue to demonstrate notable ADHD symptoms as...
. In Australia dextroamphetamine is indicated for adult ADHD treatment. While Atomoxetine is also indicated for the treatment in AustraliaAustraliaAustralia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
, it represents only a minor percentage of the drugs prescribed for the condition, due to its prohibitively high price, and it not being currently subsidised by the Government's Pharmaceutical Benefits SchemePharmaceutical Benefits SchemeThe Pharmaceutical Benefits Scheme or PBS is a program of the Australian Government that provides subsidised prescription drugs to residents of Australia. The PBS ensures that all Australians have affordable and reliable access to a wide range of necessary medicines.-History:The PBS was established...
. By contrast, the stimulant medications methylphenidateMethylphenidateMethylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
and dextroamphetamineDextroamphetamineDextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
are. Stimulants are also used off-label to treat depression, usually in conjunction with a standard antidepressantAntidepressantAn antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
drug.
Veterinary medicine
The veterinarianVeterinarian
A veterinary physician, colloquially called a vet, shortened from veterinarian or veterinary surgeon , is a professional who treats disease, disorder and injury in animals....
has a much smaller pharmacopeia available than does the human practitioner
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
. 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
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
, equine veterinarians are forced to use many drugs off-label, as the horse is classified as a "food-producing animal" and many veterinary drugs are labeled specifically not for use in animals intended for human consumption.
This practice is permitted by the Animal Medicinal Drug Use Clarification Act of 1994 (P.L. 103-396). FDA specifically prohibits extralabel use of a number of antibiotics, anti-inflammatory drugs and hormones in food producing animals. FDA also tightly controls the use of certain veterinary-prescribed drugs when administered in the feed of food-producing animals.
Research relating to off-label use
According to a national random mail survey of 599 primary care physicians and 600 psychiatrists, there is a strong indication between a physician’s belief that a use is FDA-approved and the known evidence supporting that use, although almost half of physicians believed one off-label use that had little or no supporting evidence. This shows that there is a need for informing physicians about the evidence supporting off-label prescriptions, although the FDA only regulates drug marketing not drug prescribing.- Alexander GC. Clinical prescribing (and off-label use) in a second-best world. Medical care. 2010;48:285-287. (Invited editorial)
- Tabarrok A. Assessing the FDA via the anomaly of off-label drug prescribing. Independent Review. 2000. V;1:25-53.
See also
- Pharmaceutical marketingPharmaceutical marketingPharmaceutical marketing , sometimes called medico-marketing, is the business of advertising or otherwise promoting the sale of pharmaceuticals or drugs. There is some evidence that marketing practices can negatively affect both patients and the health care profession...
- U.S. Food and Drug Administration
Largent EA, Miller FG, Pearson SD. "Going Off-label Without Venturing Off-Course: Evidence and Ethical Off-label Prescribing." Arch Intern Med. 2009;169:1745-1747.
Mortenson LE. "The off-label debate: a threat to the future of cancer care." Cancer Invest. 1991;9:597-599.