carprofen

Carprofen was used in humans for almost ten years, starting in 1988, for the same conditions as in dogs; namely, joint pain and inflammation. Side effects tended to be mild, usually consisting of nausea or gastrointestinal pain and diarrhoea. It was available by prescription in 150 mg to 600 mg doses.{{Cite web|url=http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2009/11/WC500011412.pdf|title=Committee for Veterinary Medicinal Products: Carprofen|website=www.EMA.Europa.eu|publisher=European Agency for the Evaluation of Medicinal Products|date=2009|access-date=5 February 2022|archive-date=5 March 2016|archive-url=https://web.archive.org/web/20160305014257/http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2009/11/WC500011412.pdf|url-status=dead}} Dosages over 250 mg were reserved for pain caused by severe trauma, such as postoperative inflammation; 150 mg doses were commonly used to relieve arthritis pain, while 200 mg doses were commonly prescribed for severe arthritis or inflammatory pain. The drug was taken orally.

Pfizer voluntarily removed the medication from the market for human use on commercial grounds.

In November 2024, the Committee for Veterinary Medicinal Products of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the veterinary medicinal product Carprofen Orion, Chewable tablet; Solution for injection, intended for Cat and Dog. The applicant for this veterinary medicinal product is Orion Corporation. Carprofen Orion is a generic of Rimadyl vet, which has been authorized in the EU since January 2003.{{cite web | title=Carprofen Orion EPAR | website=European Medicines Agency (EMA) | date=7 November 2024 | url=https://www.ema.europa.eu/en/medicines/veterinary/EPAR/carprofen-orion | access-date=10 November 2024}}

Carprofen is a nonsteroidal anti-inflammatory drug approved for use in dogs.{{Cite web|title=Animal Drugs @ FDA - NSAID labels|url=https://AnimalDrugsAtFDA.FDA.gov/adafda/views/#/nsaidLabels|website=AnimalDrugsAtFDA.FDA.gov|publisher=US FDA|access-date=16 November 2021}} It aids in the relief of inflammation, pain, and fever. Carprofen can be administered in pill, chewable tablet, or injection form.{{Cite web| vauthors = Burke A |date=10 November 2016|title=Rimadyl for Dogs – uses, side effects & alternatives|url=https://www.AKC.org/expert-advice/health/rimadyl-for-dogs/|website=American Kennel Club|access-date=16 November 2021}}

Carprofen can be used for long-term pain management of such conditions as osteoarthritis, which is common in canine patients, or after surgical procedures for relief of acute pain and inflammation.{{Cite web|title=Rimadyl|url=https://www.ZoetisPetCare.com/products/rimadyl|website=www.ZoetisPetCare.com|access-date=16 November 2021}}

In animals suffering from pain, carprofen has been shown to improve energy, activity level, comfort, and general well-being.

Most dogs respond well to carprofen use, but like all NSAIDs, it can cause gastrointestinal, liver, and kidney problems.{{cite journal | vauthors = Reimer ME, Johnston SA, Leib MS, Duncan RB, Reimer DC, Marini M, Gimbert K | title = The gastroduodenal effects of buffered aspirin, carprofen, and etodolac in healthy dogs | journal = Journal of Veterinary Internal Medicine | volume = 13 | issue = 5 | pages = 472–477 | date = September 1999 | pmid = 10499732 | doi = 10.1111/j.1939-1676.1999.tb01465.x | doi-access = free }}

In 1999, the Food and Drug Administration (FDA) received more than six thousand anecdotal reports of sudden animal death after usage of Pfizer's Rimadyl brand of carprofen. In response, the FDA requested that Pfizer advise consumers in their advertising that death is a possible side effect;{{Cite web|url=https://www.FDA.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm129408.htm|title=Update on Rimadyl|website=www.FDA.gov|publisher=FDA's Center for Veterinary Medicine|date=1 December 1999|access-date=16 December 2019|url-status=dead|archive-url=https://web.archive.org/web/20140908220655/http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm129408.htm|archive-date=8 September 2014}} Pfizer refused and pulled their advertising, later including death as a possible side effect on the drug label.{{cite journal | vauthors = Luna SP, Basílio AC, Steagall PV, Machado LP, Moutinho FQ, Takahira RK, Brandão CV | title = Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs | journal = American Journal of Veterinary Research | volume = 68 | issue = 3 | pages = 258–264 | date = March 2007 | pmid = 17331014 | doi = 10.2460/ajvr.68.3.258 | doi-access = free }}

Adverse effects can include:

• Loss of appetite
• Vomiting
• Diarrhea
• Increase in thirst
• Increase in urination
• Fatigue and/or lethargy (drowsiness)
• Loss of coordination
• Seizures
• Liver dysfunction: jaundice (yellowing of eyes)
• Blood or dark tarry material in urine or stools
• Lethargy
• Staggering, stumbling, weakness or partial paralysis, full paralysis{{Cite web|title=A review of signs of a potentially life-threatening reaction to Rimadyl|url=http://www.srdogs.com/Pages/rimadyl.ade.steps.html|website=www.srdogs.com|access-date=20 May 2010}}
• Change in skin (redness, scabs, or scratching)
• Change in behavior (such as decreased or increased activity level, seizure or aggression){{Cite web|title=Dog owner information about Rimadyl (carprofen)|url=https://www.rimadyl.com/display.aspx?drug=RC&species=CN&sec=610|website=www.Rimadyl.com|publisher=Pfizer|access-date=20 May 2010|archive-date=15 July 2011|archive-url=https://web.archive.org/web/20110715184915/https://www.rimadyl.com/display.aspx?drug=RC&species=CN&sec=610|url-status=dead}}
• In rare situations, death has been associated with some of the adverse reactions listed above.{{Cite news |title=Carprofen For Dogs: Dosage, Side Effects, And Alternatives |language=en |work=Relievet |url=https://www.relievet.com/blogs/tips/side-effects-of-carprofen-for-dogs-dosage |access-date=2022-07-21}}

Effects of overdose include gastritis and ulcer formation.{{Cite web|title=Generic dog Rimadyl online|url=http://RimadylOnline.com/|website=RimadylOnline.com|url-status=dead|archive-url=https://web.archive.org/web/20110715184803/http://rimadylonline.com/|archive-date=15 July 2011|access-date=15 July 2011}}

In healthy dogs given carprofen, no perioperative adverse effects on the cardiovascular system have been reported at recommended dosages.{{cite journal | vauthors = Boström IM, Nyman GC, Lord PE, Häggström J, Jones BE, Bohlin HP | title = Effects of carprofen on renal function and results of serum biochemical and hematologic analyses in anesthetized dogs that had low blood pressure during anesthesia | journal = American Journal of Veterinary Research | volume = 63 | issue = 5 | pages = 712–721 | date = May 2002 | pmid = 12013473 | doi = 10.2460/ajvr.2002.63.712 | doi-access = free }}{{cite journal | vauthors = Frendin JH, Boström IM, Kampa N, Eksell P, Häggström JU, Nyman GC | title = Effects of carprofen on renal function during medetomidine-propofol-isoflurane anesthesia in dogs | journal = American Journal of Veterinary Research | volume = 67 | issue = 12 | pages = 1967–1973 | date = December 2006 | pmid = 17144795 | doi = 10.2460/ajvr.67.12.1967 | doi-access = free }} Perioperative administration of carprofen to cats did not affect postoperative respiratory rate nor heart rate.{{cite journal | vauthors = Höglund OV, Dyall B, Gräsman V, Edner A, Olsson U, Höglund K | title = Effect of non-steroidal anti-inflammatory drugs on postoperative respiratory and heart rate in cats subjected to ovariohysterectomy | journal = Journal of Feline Medicine and Surgery | volume = 20 | issue = 10 | pages = 980–984 | date = October 2018 | pmid = 29165006 | doi = 10.1177/1098612X17742290 | s2cid = 30649716 | pmc = 11129237 }}

Carprofen should not be administered concurrently with steroids, 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). Carprofen should not be given at the same time with other types of medications, such as other NSAIDs (aspirin, etodolac, deracoxib, meloxicam, tepoxalin), or steroids such as dexamethasone, triamcinolone, cortisone, or prednisone.{{Medical citation needed|date=February 2022}}

Carprofen must be used with caution within the supervision of a veterinarian in dogs with liver or kidney disease, dehydration, bleeding deficits, or other health problems. It is not recommended for use in dogs with bleeding disorders (such as Von Willebrand's disease), as safety has not been established in dogs with these disorders.{{Cite web|title=Rimadyl (Carprofen)|url=http://www.VetDepot.com/Rimadyl-Carprofen-25mg-60-Caplets.html|website=www.VetDepot.com|publisher=Vet Depot|url-status=dead|archive-url=https://web.archive.org/web/20100523014832/http://www.vetdepot.com/Rimadyl-Carprofen-25mg-60-Caplets.html|archive-date=23 May 2010|access-date=20 May 2010}} 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 have been conducted to establish the safety of using carprofen. Clinical studies were conducted in nearly 300 dogs of different breeds. 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.{{Cite web|date=2007|title=Rimadyl [package insert]|url=https://www.rimadyl.com/account/DisplayPDF?docName=PI.pdf|website=www.Rimadyl.com|location=New York|publisher=Pfizer Animal Health|access-date=13 August 2014|archive-date=8 July 2014|archive-url=https://web.archive.org/web/20140708155003/https://www.rimadyl.com/account/DisplayPDF?docName=PI.pdf|url-status=dead}}{{Medical citation needed|date=February 2022|reason=Independent professional citation needed}}

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;{{Cite web|title=Get the facts about pain relievers for pets|url=https://www.FDA.gov/animal-veterinary/animal-health-literacy/get-facts-about-pain-relievers-pets|website=www.FDA.gov|publisher=Center for Veterinary Medicine|date=3 November 2020}}
• Senior dog use. Older dogs are generally more prone to side effects caused by carprofen.{{Medical citation needed|date=February 2022|reason=Independent professional citation needed}}

Carprofen may be administered intravenously to horses.{{Cite journal|vauthors=McIlwraith CW, Frisbie DD, Kawcak CE|date=2001|title=Nonsteroidal Anti-Inflammatory Drugs|journal= Proc. AAEP|issue=47|pages=182–187}} A single dose has been shown to reduce prostaglandin E2 production and inflammatory exudate for up to 15 hours,{{cite journal | vauthors = Lees P, McKellar Q, May SA, Ludwig B | title = Pharmacodynamics and pharmacokinetics of carprofen in the horse | journal = Equine Veterinary Journal | volume = 26 | issue = 3 | pages = 203–208 | date = May 1994 | pmid = 8542839 | doi = 10.1111/j.2042-3306.1994.tb04370.x }} although there was less effect on eicosanoid production when compared to the effects produced by NSAIDs such as phenylbutazone or flunixin.{{cite journal | vauthors = Lees P, Ewins CP, Taylor JB, Sedgwick AD | title = Serum thromboxane in the horse and its inhibition by aspirin, phenylbutazone and flunixin | journal = The British Veterinary Journal | volume = 143 | issue = 5 | pages = 462–476 | date = 1987 | pmid = 3119142 | doi = 10.1016/0007-1935(87)90024-8 }} Prostaglandin E2 and inflammatory exudate are also reduced and leukotriene B4 is inhibited. Carprofen can also be given orally, but intramuscular use may produce muscle damage.{{cite journal | vauthors = McKellar QA, Bogan JA, von Fellenberg RL, Ludwig B, Cawley GD | title = Pharmacokinetic, biochemical and tolerance studies on carprofen in the horse | journal = Equine Veterinary Journal | volume = 23 | issue = 4 | pages = 280–284 | date = July 1991 | pmid = 1915228 | doi = 10.1111/j.2042-3306.1991.tb03718.x }}

Carprofen is used as an analgesic for mouse surgical procedures.{{Cite journal |last=Adamson |first=Trinka |date= 2010|title=Assessment of Carprofen and Buprenorphine on Recovery of Mice after Surgical Removal of the Mammary Fat Pad |journal=J Am Assoc Lab Anim Sci|volume=49 |issue=5 |pages=610–616 |pmid=20858363 |pmc=2949431 }} Carprofen may also be used on adult fish.{{Cite journal |last=Uney |first=Kamil |title=Pharmacokinetics and Bioavailability of Carprofen in Rainbow Trout (Oncorhynchus mykiss) Broodstock |journal=Pharmaceutics|date=2021 |volume=13 |issue=7 |page=990 |doi=10.3390/pharmaceutics13070990 |doi-access=free |pmid=34208822 |pmc=8309133 }}

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.{{Cite web|url=http://c.ymcdn.com/sites/www.aavpt.org/resource/resmgr/imported/carprofen.pdf|title=Carprofen (Veterinary – Systemic)|publisher=The United States Pharmacopeial Convention|date=2007}} and more recent a 50 mg Caplet called Carprox for senior dogs aged 10 years+.

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