Carprofen

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Carprofen

File:Carprofen.svg
Clinical data
AHFS/Drugs.com	FDA Professional Drug Information
ATCvet code	Template:Infobox drug/formatATCvet Template:Infobox drug/formatATCvet
Legal status
Legal status	US: Veterinary use only. It was -only in humans.
Pharmacokinetic data
Protein binding	High (99%)
Elimination half-life	Approximately 8 h (range 4.5–9.8 h) in dogs
Identifiers
IUPAC name (RS)-2-(6-Chloro-9H-carbazol-2-yl)propanoic acid
CAS Number	53716-49-7 Y
PubChem CID	2581
IUPHAR/BPS	7141
DrugBank	DB00821 Y
ChemSpider	2483 Y
UNII	FFL0D546HO
KEGG	D03410 Y
ChEBI	CHEBI:364453 Y
ChEMBL	ChEMBL1316 Y
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C15H12ClNO2
Molar mass	273.714 g/mol
3D model (JSmol)	Interactive image
SMILES O=C(O)C(c3ccc2c1cc(Cl)ccc1nc2c3)C
InChI InChI=1S/C15H12ClNO2/c1-8(15(18)19)9-2-4-11-12-7-10(16)3-5-13(12)17-14(11)6-9/h2-8,17H,1H3,(H,18,19) Y Key:PUXBGTOOZJQSKH-UHFFFAOYSA-N Y
(verify)

Overview

File:Rimadyl pill 100 mg.jpg

A 100 mg Rimadyl pill approximately 19 mm (0.75 in) wide and 8.6 mm (0.34 in) thick, sold in the United States

Carprofen (marketed as Vetprofen, Rimadyl, Imadyl, Novox, Imafen and Rovera) is a non-steroidal anti-inflammatory drug that veterinarians prescribe as a supportive treatment for various conditions. It provides day-to-day treatment for pain and inflammation from arthritis in geriatric dogs, joint pain, osteoarthritis, hip dysplasia, and other forms of joint deterioration.

It is also used to relieve short-term post-operative pain, inflammation, and swelling after spaying, neutering, and other procedures. Carprofen reduces inflammation by inhibition of COX-2 and other sources of inflammatory prostaglandins. This is targeted protection, in that it does not interfere with COX-1 activity.

Administration

Carprofen is available in the USA in 25, 75 and 100 mg tablets (given with food or fed directly to the animal), and in injectable form. In the UK, it is available in 20, 50 and 100 mg tablets. The usual dosage is 4.4 mg per kilogram (2.0 mg/lb) daily.

In Australia, carprofen is marketed as Norocarp or Tergive Injection. Norocarp is available in 20 mg and 50 mg tablets or Norophen in injectable liquid at 5.0% w/v, for cattle and canines. Carprofen is also marketed in many Latin-American (and some Asian and African countries) as Carprodyl in 25 mg and 100 mg tablets for canines and Carprobay in 20 mg and 50 mg tablets for dogs.

Carprofen is sometimes divided between morning and evening doses. It is administered two hours before surgery for post-operative pain.

Health issues

Most dogs respond well to carprofen use, but like all non-steroidal anti-inflammatory (NSAID) medications used in humans and animals, it is capable of causing gastrointestinal, liver and kidney problems in some patients.

After introduction, significant anecdotal reports of sudden animal deaths from its use arose. To date, the FDA has received more than 6,000 adverse reaction reports about the drug (manufactured by Pfizer). 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.

Pfizer acknowledges a problem with some dog owners, especially a consumer group that mounted a campaign dubbed BARKS, for Be Aware of Rimadyl's Known Side-effects—which include loss of appetite, wobbling, vomiting, seizures, and severe liver malfunction. Reports say the drug company has contacted pet owners who told their stories on the Internet, offering to pay medical and diagnostic expenses for dogs that carprofen may have harmed.

Symptoms to watch for include:

• Loss of appetite
• Vomiting
• Diarrhea
• Increase in thirst
• Increase in urination
• Fatigue and/or Lethargy
• Loss of coordination
• Seizures

Other symptoms worth discussing with a vet include excessive drinking or urination, blood or dark tar-like material in urine or stools, jaundice (yellowing of eyes), and unusual lethargy.

Other side effects of Rimadyl include:

• Black, tarry stools or flecks of blood in the vomit
• Drowsiness
• Staggering, stumbling, weakness or partial paralysis, full paralysis, dizziness, loss of balance.
• Change in urination habits (frequency, color, or smell)
• Change in skin (redness, scabs, or scratching)
• Change in behavior (such as decreased or increased activity level, seizure or aggression).

Excess use of Rimadyl can lead to gastritis and ulcer formation. It is also believed that in some breeds of dogs it may induce kidney and liver damage.

Carprofen should not be administered to animals that are also being given steroids (one of the primary risks of this combination being that it can cause ulcers in the stomach). In dogs, it is recommended that the dog be taken off carprofen for three full days before ingesting a steroid (such as prednisolone).

According to the official Rimadyl website, the drug 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. However, dog owners whose pets have been administered Rimadyl and have experienced side effects are highly recommended to contact a veterinarian as soon as they appear and to stop the therapy.

Also, Rimadyl must be used with caution and within the closely monitoring of a veterinarian in dogs with liver or kidney disease, dehydration, bleeding deficits, or other health problems. Rimadyl 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. Also, it has been not yet established if Rimadyl can be safely used in pregnant dogs, dogs used for breeding purposes or in lactating female dogs.

Several laboratory studies and clinical trials have been conducted to establish the safety of using Rimadyl. Clinical studies were conducted in nearly 300 dogs, coming from different breeds. These dogs have been treated with Rimadyl at the recommended dose for 2 weeks. According to these studies, the drug was clinically well tolerated and dogs treated with Rimadyl did not have a greater incidence of adverse reactions when compared to the placebo-treated animals.

There are a number of factors that might however contribute to the high incidence of adverse drug experience reports received for Rimadyl by the Center for Veterinary Medicine in the late 1990s. These include:

• The type of drug;
• Wide use;
• Duration of use. While the side effects from Rimadyl are known to occur within a short period of time after administration, it is believed that long-term use may actually result in a higher risk for adverse reactions;
• Senior dog use. Older dogs are generally more prone to side effects caused by carprofen.

Human use

Carprofen was used in humans for almost 10 years, starting in 1988. It was used for the same conditions as in dogs, viz., joint pain and inflammation. The human body accepted the drug well and side effects tended to be mild, usually consisting of nausea or gastro-intestinal pain and diarrhea. For human use, Rimadyl was available only by prescription in 150 to 600 mg doses. Dosage over 250 mg was only for relieving pain after severe trauma, such as post-surgery inflammation. 150 mg doses were commonly used to relieve the pain of arthritis, while 200 mg doses were commonly prescribed in cases of severe arthritis or severe inflammation pain. The drug was taken orally. Pfizer voluntarily pulled it from the market for human use on commercial grounds.

Equine use

Carprofen is given intravenously to horses at a dose of 0.7 mg/kg once daily. 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 production when compared to the effects produced by NSAIDs such as phenylbutazone or flunixin. Prostaglandin E2 and inflammatory exudate are better reduced at a dose of 4 mg/kg IV, with the added benefit of inhibition of leukotriene B4. Carprofen can also be given orally, but intramuscular use may produce muscle damage.

External links

• Rimadyl warning
• Pfizer product website PDS
• Senior dogs and Rimadyl