CARPROFEN

Chemistry - A propionic acid derivative non-steroidal antiinflammatory agent, carprofen occurs asa white crystalline compound. It is practically insoluble in water and freely soluble in ethanol atroom temperature.

Storage, Stability, Compatibility

The commercially available caplets should be stored at roomtemperature (15-30°C).

Pharmacology - CARPROFEN

Like other NSAIDs, carprofen exhibits analgesic, anti-inflammatory, and antipyretic activity probably through its inhibition of cyclooxygenase, phospholipase A2 and inhibition of prostaglandin synthesis.
Uses, Indications - Carprofen is indicated for the relief of pain and inflammation in dogs. It mayalso prove to be of benefit in other species as well, but data are scant to support its safe use at thistime. In Europe, carprofen is reportedly registered for single dose use in cats, but there have beenreported problems (e.g., vomiting) with cats receiving more than a single dose.

Pharmacokinetics - CARPROFEN

When administered orally to dogs, carprofen is approximately 90%bioavailable. Peak serum levels occur between 1-3 hours post dosing. The drug is highly bound toplasma proteins (99%) and has a low volume of distribution (0.12 - 0.22 l/kg). Carprofen is extensively metabolized in the liver primarily via glucuronidation and oxidative processes. About 70-80% of a dose is eliminated in the feces; 10-20% eliminated in the urine. Some enterohepatic recycling of the drug occurs. Elimination half-life of carprofen in the dog is approximately 8-12 hours.

Contraindications, Precautions, Reproductive Safety

Carprofen is contraindicated in dogswith bleeding disorders (e.g., Von Willebrand's), those that have had prior serious reactions to it orother propionic-class antiinflammatory agents. It should be used with caution in geriatric patients orthose with preexisting chronic diseases (e.g., inflammatory bowel disease, renal or hepaticinsufficiency).

Adverse Effects, Warnings

Although adverse effects appear to be uncommon with carprofen usein dogs, they can occur. Mild gastrointestinal effects are the most likely to appear, but seriouseffects (hepatocellular damage and/or renal disease; hematologic and serious gastrointestinal effects) have been reported. Geriatric dogs or dogs with chronic diseases (e.g., inflammatory bowel disease, renal or hepatic insufficiency) may be at greater risk for developing toxicity while taking this drug. Although not proven to be statistically significant, Labrador Retrievers have been associated with 1/3 of the initial cases associated with the reported hepatic syndrome. Before initiating therapy, pre-treatment patient evaluation and discussion with the owner regarding the potential risks versus benefits of therapy are strongly advised.
Overdosage - In dog toxicologic studies, repeated doses of up to 10X resulted in little adversity.
Some dogs exhibited hypoalbuminemia, melena or slight increases in ALT. However, post-marketing surveillance suggests that there may be significant interpatient variability in response to acute or chronic overdoses.

Drug Interactions

Note: Although the manufacturer does not list any specific drug interactionsin the package insert, it does caution to avoid or closely monitor carprofen's use with other ulcerogenic drugs (e.g., corticosteroids or other NSAIDs).
In humans, there are many interactions possible with NSAIDs. Because clinical experience islimited in dogs, the following may or may not be clinically significant: Because carprofen is highlybound to plasma proteins (99%) it may displace other highly bound drugs. Increased serum levelsand duration of actions of phenytoin, valproic acid, oral anticoagulants, other antiinflammatory agents, salicylates, sulfonamides, and the sulfonylurea antidiabetic agentsmay occur.
When aspirin is used concurrently with carprofen, plasma levels of carprofen could decrease andan increased likelihood of GI adverse effects (blood loss) could occur. Concomitant administrationof aspirin with carprofen cannot be recommended.
Probenecid may cause a significant increase in serum levels and half-life of carprofen.
Serious toxicity has occurred when NSAIDs have been used concomitantly with methotrexate;use together with extreme caution.
Carprofen may reduce the saluretic and diuretic effects of furosemide and increase serum levelsof digoxin. Use with caution in patients with severe cardiac failure.