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PHARM PROFILE

CARPROFEN* Josephine P. Isaacs, MPharm, FACPP The University of Queensland Brisbane, Queensland, Australia

C

arprofen is a nonsteroidal antiinflammatory drug (NSAID) of the propionic acid class that is used to treat pain and inflammation in dogs.

Pharmacology Carprofen has antiinflammatory, analgesic, and antipyretic actions and is more potent than aspirin, ibuprofen, and phenylbutazone. Inhibition of cyclooxygenase (COX) and prostaglandin (PG) synthesis are at least partly responsible for its action. Carprofen is a mild inhibitor of COX compared with the older NSAIDs; other mechanisms, including phospholipase A 2 inhibition and neutrophil migration inhibition, are thought to contribute to its relatively potent antiinflammatory effect.1,2 In dogs, carprofen is highly protein bound, has a small volume of distribution, and is metabolized by the liver and eliminated predominantly by biliary excretion as glucuronide conjugates. Enterohepatic recycling has been shown to occur in dogs, and the extent may vary with different physiologic conditions.1,3,4

Indications Carprofen is indicated for the treatment of pain and inflammation in dogs, such as in degenerative joint disease.5,6 Cautions Adverse Drug Reactions Carprofen has a more favorable

COX-2:COX-1 ratio than do older NSAIDs. It inhibits inflammatory PG to a greater extent than protective PG, potentially explaining the lower frequency of major gastrointestinal (GI; ulceration, hemorrhage) and renal toxicity. GI reactions include vomiting, anorexia, diarrhea, melena, and ul-

TABLE ONE Drugs that Interact with Nonsteroidal Antiinflammatory Drugs (NSAIDs) in Humans Drug

Risk

Diuretics

NSAID toxicity; possible decreased response to diuretics

Angiotensin-converting enzyme (ACE) inhibitors

Possible decreased response to ACE inhibitors

Digoxin

Digoxin toxicity if renal function is decreased; monitor serum digoxin

Corticosteroids

Gastrointestinal ulceration and renal toxicity

Other NSAIDs

Increased risk of all adverse reactions to NSAIDs

Aminoglycosides

Renal toxicity

Cisplatin

Cisplatin toxicity

Methotrexate

Reduced renal excretion of methotrexate; methotrexate toxicity

*Since this column was written, another nonsteroidal antiinflammatory drug has been approved for use in animals. Look for a Pharm Profile column on etodolac this summer.

Pharm Profile introduces drugs that are new to the veterinary market as well as new indications for existing drugs. If you would like Pharm Profile to cover a particular agent, please contact column editor GiGi Davidson, BS, RPh, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606; phone 919-821-9500 • fax 919-829-4225 • email [email protected].

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Client Counseling Information ■ Carprofen relieves pain and reduces inflammation. It is used to treat the symptoms of joint and back problems (osteoarthritis) in dogs. Carprofen belongs to the class of drugs called nonsteroidal antiinflammatory drugs. ■ Carprofen is generally well tolerated by dogs. In a small number of dogs, however, side effects may occur. If you see any of the following signs— lack of appetite, vomiting, lethargy, diarrhea, or blood in stools—stop administering the drug immediately and contact your veterinarian. ■ Tell your veterinarian if you give any other medicines to your dog. Other medicines for pain relief, such as aspirin, must not be given at the same time as carprofen.

ceration. Renal effects include azotemia, electrolyte and acid–base disturbances, oliguria, polyuria, renal tubular necrosis, and acute renal failure. Hepatic effects include increased liver enzymes, increased serum bilirubin, and hepatocellular necrosis.7 Of 21 reported cases of hepatocellular necrosis in dogs, 13 patients were Labrador retrievers; this is believed to be an idiosyncratic reaction unrelated to dosage and duration of administration. Additional reactions include lethargy and behavioral changes. Adverse effects are extremely rare and generally mild in dogs. One field study of 297 dogs reported an incidence of adverse effects of 1.3% (not higher than that in control dogs).6 Other than Macphail and coworkers,7 I am not aware of any case reports or studies of the adverse effects of carprofen in dogs.

Precautions and Contraindications Animals with renal, cardiac, and hepatobiliary disease are more at risk of developing adverse reactions because they may have reduced renal and circulatory output as well as electrolyte and water imbalances. Like other NSAIDs, carprofen may inhibit renal PGs that help maintain renal perfusion. Carprofen should be used with extreme caution in dogs

with a history of GI bleeding. The drug should not be used in dehydrated, hypovolemic, or hypotensive animals because it increases the risk of renal toxicity in such conditions. Carprofen is contraindicated in animals with bleeding disorders, such as von Willebrand’s disease, because safe use in these conditions has not been established. Similarly, carprofen should not be used in cats because its safety has not been adequately established; there have been anecdotal reports of side effects, especially GI and renal, after short-term oral use in cats.

Use in Pregnant and Lactating Bitches Carprofen is not recommended for use in pregnant or lactating bitches. Specific studies of the use of carprofen in pregnant or lactating bitches have not been conducted. Acute Toxicity There are no published reports of acute toxicity from carprofen overdose in dogs. Very high doses were well tolerated in preclinical trials in healthy dogs; dosages of 25 mg/kg/day for 42 days or 40 mg/kg/day for 14 days did not cause any significant clinical abnormalities.6 In the case of an overdose, however, supportive measures should be

Small Animal/Exotics

employed. Vomiting should be induced or gastric lavage used if the animal is presented within a short time after ingestion. Activated charcoal reduces absorption. Supportive care includes maintaining hydration and administering a cytoprotective drug, such as sucralfate (0.5 to 1 g two or three times daily). The animal should be monitored closely for adverse GI, renal, and hepatic effects.

Drug Interactions In humans, NSAIDs are known to interact with many drugs 8 (Table One). Although interactions have not been reported specifically for carprofen, care should be taken with all of the drugs listed in Table One. Dosage and Administration Carprofen is dosed at 2.2 mg/kg (1 mg/lb) orally twice daily. Preparation Rimadyl® (Pfizer Animal Health, Exton, PA) scored caplets contain 25, 75, or 100 mg of carprofen and are available in bottles of 100 and 250 caplets. Storage and Handling Carprofen should be stored at a controlled room temperature of 15˚C to 30˚C (59˚F to 86˚F) in a dry place out of direct sunlight. The drug should also be kept out of the reach of children. References 1. Baruth H, Berger L, Bradshaw D, et al: Carprofen, in Rainsford KD (ed): Antiinflammatory and Anti-rheumatic Drugs. Volume II. Newer Anti-inflammatory Drugs. Boca Raton, FL, CRC Press, 1986, pp 33–47. 2. Johnston SA, Budsberg SC: Nonsteroidal anti-inflammatory drugs and corticosteroids for the management of canine osteoarthritis. Vet Clin North Am 27:841– 861, 1997. 3. McKellar QA, Pearson T, Bogan JA, et al: Pharmacokinetics, tolerance and serum thromboxane inhibition of carprofen in the dog. J Small Anim Pract 31:443–448, 1990.

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4. Priymenko N, Garnier F, Ferre J-P, et al: Enantioselectivity of the enterohepatic recycling of carprofen in the dog. Drug Metab Disposition 26:170–176, 1998. 5. Vasseur PB, Johnson AL, Budsberg SC, et al: Randomized, controlled trial of the efficacy of carprofen, a nonsteroidal anti-inflammatory drug, in the treatment of osteoarthritis in the dogs. JAVMA 206(6):807–811, 1995. 6. Fox SM, Johnston SA: Use of carprofen for the treatment of pain and inflammation in dogs. JAVMA 210(10):1493–1497, 1997. 7. Macphail CM, Lappin MR, Meyer DJ, et al: Hepatocellular toxicosis

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associated with administration of carprofen in 21 dogs. JAVMA 212 (12):1895–1901, 1998. 8. Verbeek RK: Pharmacokinetic drug interactions with nonsteroidal anti-inflammatory drugs. Clin Pharmacokinet 19(1):44–66, 1990.

About the Author Ms. Isaacs is a pharmacist at the Veterinary Teaching Hospital, School of Veterinary Science, The University of Queensland, Brisbane, Queensland, Australia.