Carprofen
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Carprofen is a
non-steroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
(NSAID) of the
propionic acid Propionic acid (, from the Greek words πρῶτος : ''prōtos'', meaning "first", and πίων : ''píōn'', meaning "fat"; also known as propanoic acid) is a naturally occurring carboxylic acid with chemical formula CH3CH2CO2H. It is a liq ...
class that was previously for use in humans and animals, but is now only available to
veterinarian A veterinarian (vet), also known as a veterinary surgeon or veterinary physician, is a medical professional who practices veterinary medicine. They manage a wide range of health conditions and injuries in non-human animals. Along with this, vet ...
s for prescribing as a supportive treatment for various conditions in only animals. Carprofen reduces inflammation by inhibition of
COX-1 Cyclooxygenase 1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the ''PTGS1'' gene. In humans it is one of two cyclooxygenases. ...
and
COX-2 Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene ...
; its specificity for COX-2 varies from species to species. Marketed under many brand names worldwide, carprofen provides day-to-day treatment for
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
and
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
from various kinds of
joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw ...
pain, as well as post-operative pain.


Human use

Carprofen was used in
humans Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
for almost ten years, starting in 1988. It was used for the same conditions as in dogs, namely
joint pain Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...
and
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
. Side effects tended to be mild, usually consisting of
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
or gastrointestinal pain and
diarrhoea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
. It was available only by prescription in 150  mg to 600 mg doses. Dosage over 250 mg was only for relieving pain after severe
trauma Trauma most often refers to: * Major trauma, in physical medicine, severe physical injury caused by an external source * Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event *Traumatic i ...
, such as post-surgery inflammation. 150 mg doses were commonly used to relieve the pain of
arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...
, while 200 mg doses were commonly prescribed in cases of severe arthritis or severe inflammation pain. The drug was taken orally.
Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
voluntarily removed it from the market for human use on commercial grounds.


Veterinary medicine


Canine use

Carprofen is one of eleven approved non-steroidal anti-inflammatory drugs for use in dogs. These are non-steroidal anti-inflammatory drugs that aid in the relief of inflammation, pain, and fever. Carprofen can be administered in a pill, chewable tablet, or injection form. Often, Carprofen is used as a long-term
pain management Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals pr ...
drug, or after a surgical procedure for acute relief of pain and inflammation during the healing process. When using long-term,
osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
is often the targeted condition, since it is common in canine patients, varying across breed, size, and age. For patients in need of acute or chronic pain management, Carprofen is seen to improve energy, activity level, comfort, and general wellbeing of the dog.


Adverse effects

Most dogs respond well to carprofen use, but like all NSAIDs, it may cause gastrointestinal, liver, and kidney problems in some patients. In 1999, the
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) in the USA had more than 6000 anecdotal reports of sudden animal death after usage of
Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
's Rimadyl brand of carprofen. As a result, the FDA requested that Pfizer advise consumers in their advertising that death is a possible side effect. Pfizer refused and pulled their advertising; however, they now include death as a possible side effect on the drug label. Plans call for a 'Dear Doctor' letter to advise veterinarians, and a safety sheet attached to pill packages. Adverse effects should be monitored and brought to your local veterinarian's attention when a patient is on an NSAID for chronic pain management. Adverse effects include: *Loss of appetite *Vomiting *Diarrhea *Increase in thirst *Increase in urination *Fatigue and / or lethargy (
drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
) *Loss of coordination *Seizures *Liver dysfunction:
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
(yellowing of eyes) *Blood or dark tar-like material in
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...
or stools *
Lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
*Staggering, stumbling, weakness or partial
paralysis Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...
, full paralysis *Change in
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
(redness, scabs, or scratching) *Change in behavior (such as decreased or increased activity level,
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
or aggression) *In rare situations, death has been associated with some of the adverse reactions listed above. Effects of overdose include
gastritis Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain (see dyspepsia). Other possi ...
and ulcer formation. In healthy dogs given carprofen, no perioperative adverse effects on the cardiovascular system have been reported at recommended dosages. Perioperative administration of carprofen to cats did not affect postoperative respiratory rate nor heart rate. Carprofen should not be administered concurrently with
steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
s, as this can cause ulcers in the stomach. Dogs should be taken off carprofen for three full days before ingesting a steroid (such as
prednisolone Prednisolone is a steroid medication used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arthrit ...
). Carprofen should not be given at the same time with other types of medications, such as other NSAIDs (
aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
,
etodolac Etodolac is a nonsteroidal anti-inflammatory drug (NSAID). It was patented in 1971 and approved for medical use in 1985. It was approved in the U.S. in 1991. Medical uses NSAIDs are used for the management of mild to moderate pain, fever, an ...
, deracoxib,
meloxicam Meloxicam, sold under the brand name Mobic among others, is a nonsteroidal anti-inflammatory medication (NSAID) used to treat pain and inflammation in rheumatic diseases and osteoarthritis. It is used by mouth or by intravenous, injection into a ...
, tepoxalin), or steroids such as
dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cav ...
,
triamcinolone Triamcinolone is a glucocorticoid used to treat certain skin diseases, allergies, and rheumatic disorders among others. It is also used to prevent worsening of asthma and COPD. It can be taken in various ways including by mouth, injection i ...
,
cortisone Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug; it is not synthesized in the adrenal glands. Cortisol is converted by the action of the enz ...
, or
prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...
. Carprofen must be used with caution within the supervision of a veterinarian in dogs with liver or kidney disease,
dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
, bleeding deficits, or other health problems. It is not recommended for use in dogs with bleeding disorders (such as
Von Willebrand's disease Von Willebrand disease (VWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor ...
), as safety has not been established in dogs with these disorders. It has not been established whether carprofen can be safely used in pregnant dogs, dogs used for breeding purposes, or in lactating dogs. Several laboratory studies and
clinical trials Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
have been conducted to establish the safety of using carprofen. Clinical studies were conducted in nearly 300 dogs of different
breeds A breed is a specific group of domestic animals having homogeneous appearance (phenotype), homogeneous behavior, and/or other characteristics that distinguish it from other organisms of the same species. In literature, there exist several slight ...
. The dogs were treated with Rimadyl at the recommended dose for two weeks. According to these studies, the drug was clinically well tolerated, and the treated dogs did not have a greater incidence of adverse reactions when compared to the control group. A number of factors may contribute to the high incidence of adverse reports received for carprofen by the Center for Veterinary Medicine in the late 1990s. These include: *The type of drug; *Wide use; *Duration of use. Long-term use can result in a higher risk for adverse reactions. It is recommended that blood tests for liver and kidney function are performed both prior to starting and regularly while on NSAIDs to monitor the patient’s tolerance; *Senior dog use. Older dogs are generally more prone to side effects caused by carprofen.


Equine use

Carprofen may be administered
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
ly to horses. A single dose has been shown to reduce prostaglandin E2 production and inflammatory exudate for up to 15 hours, although there was less effect on
eicosanoid Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a s ...
production when compared to the effects produced by NSAIDs such as
phenylbutazone Phenylbutazone, often referred to as "bute", is a nonsteroidal anti-inflammatory drug (NSAID) for the short-term treatment of pain and fever in animals. In the United States and United Kingdom, it is no longer approved for human use (except in th ...
or
flunixin Flunixin is a nonsteroidal anti-inflammatory drug (NSAID), analgesic, and antipyretic used in horses, cattle and pigs. It is often formulated as the meglumine salt. In the United States, it is regulated by the U.S. Food and Drug Administration ( ...
. Prostaglandin E2 and inflammatory exudate are also reduced and
leukotriene B4 Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice. Biochemistry Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It is produced from leukocytes in r ...
is inhibited. Carprofen can also be given orally, but intramuscular use may produce muscle damage.


Brands and dosage forms for veterinary use

It is marketed under many brand names including: Acticarp, Artriofin, Austiofen, Bomazeal, Canidryl, Carporal, Carprieve, Carprocow, Carprodolor, Carprodyl, Carprofelican, Carprofen, Carprofène, Carprofeno, Carprofenum, Carprogesic, Carprosol, Carprotab, Carprox, Comforion, Dolagis, Dolocarp, Dolox, Eurofen, Kelaprofen, Librevia, Norocarp, Norodyl, Novocox, Ostifen, Prolet, Quellin, Reproval, Rimadyl, Rimifin, Rofeniflex, Rovera, Rycarfa, Scanodyl, Tergive, Vetprofen, and Xelcor. Veterinary dosage forms include 25  mg, 75 mg, and 100 mg tablets, and 50 mg per mL injectable form.


References


External links

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