Pamela A. Davol, 76 Mildred Avenue, Swansea,
At some point in every dog's life, whether during his rapid growth phase of puppyhood, following an injury, or during his senior years, he will experience pain and inflammation of joints which will produce symptoms of stiffness and/or lameness. Because ability for activity is a key component to a dog's quality of life, for many years, dog owners have relied on anti-inflammatory medications designed for humans to treat dogs suffering from "growing pains", connective tissue injuries, and degenerative joint diseases (osteoarthritis). Recently, however, Pfizer Pharmaceuticals has introduced an anti-inflammatory drug called Rimadyl which has been designed and approved by the FDA specifically for use in canines. This drug was found to have minimal adverse reactions during investigational studies and has been clinically shown to significantly relieve symptoms associated with pain and inflammation. However, results from widespread clinical use of Rimadyl came to suggest that, although occurring with low frequency, the Labrador Retriever, as a breed, demonstrated a higher predisposition for liver toxicity associated with use of Rimadyl compared to all other breeds. The following is presented to provide information regarding the benefits of Rimadyl, discuss whether the cause for concern for use of Rimadyl in Labrador Retrievers is warranted, and alert owners of all dogs receiving Rimadyl-treatment to warning signs which may be indicative of adverse reactions.
Stress on bone, whether the result of many years of weight bearing, bone abnormalities such as improper fit of joints (as occurs in hip dysplasia) or accidental injuries, leads to softening and roughening of joint cartilage which serves as a protective covering for bones. Eventually the cartilage cracks and exposes the bone which becomes further susceptible to erosion. The body's attempt to regenerate new bone causes the area of damaged bone to become very hard. Additionally, the body employs a number of physiological mechanisms in an attempt to heal the damage. One of these mechanisms includes dilation of blood vessels in an effort to increase blood flow to the site of regeneration. Though the increased blood flow brings more nutrients and oxygen required for cellular repair mechanisms, it also causes swelling, which adds pressure to the injury, and initiates surrounding cells to release chemical substances, which act on nerve endings. These two conditions are the sources for inflammation and pain, respectively.
Prostaglandins, one of the chief chemical substances released by cells following injury, are formed from polyunsaturated fatty acids and are hormone-like in their ability to have diverse effects on a number of body functions. Among these effects, prostaglandins play a central role in inflammation and pain, therefore, drugs which inhibit prostaglandin synthesis are valued for their ability to provide pain relief. Anti-prostaglandin drugs include analgesics such as aspirin and acetaminophen, as well as other non-steroidal anti-inflammatories (NSAIDS) such as propionic acids which include ibuprofen and naproxen.
Previously, treatment of pain and inflammation in the canine species has been limited to treatment with drugs specifically designed and tested for the human metabolism. However, drugs which are maximally absorbed, and therefore therapeutically effective, by the human gastrointestinal system are often not absorbed efficiently by the carnivore-digestive-tract of the dog. Additionally, sensitivity of the canine stomach to acidity, a characteristic of most analgesics and NSAIDS, provides limitations to compensating for absorption by increasing dosage. It is also for this reason that buffered aspirin has been the first choice for over-the-counter pain relief in dogs. Though the analgesic, acetaminophen (Tylenol), is prescribed by some veterinarians in lieu of other anti-inflammatories with the intent to avoid stomach-irritation, other vets do not recommend its use in dogs, since therapeutic effectiveness, as well as adverse reactions have never been clinically investigated in dogs. (It should be noted that the coating of encapsulated acetaminophen will not be digested until it is well into the latter-half of the small intestine, therefore, absorption of drug is minimal at best).
Rimadyl, also known as carprofen, is a NSAID belonging to the same class as ibuprofen and naproxen which has been specifically designed, tested, and FDA approved for treatment of pain and inflammation in dogs. In investigational studies, dogs given Rimadyl demonstrated significant improvement in symptoms without significant adverse reactions compared to placebo-treated dogs. Rimadyl is now being widely used for the clinical treatment of dogs to control symptoms of stiffness and lameness associated with the pain and inflammation of bone disorders and degenerative arthritis.
Because prostaglandins play a role not only in pain and inflammatory responses, but also in blood pressure, clotting ability, smooth muscle contraction, etc., use of anti-prostaglandin drugs may have adverse effects, particularly in individuals with underlying health disorders. Therefore, Rimadyl should not be used in dogs with bleeding disorders and neither should it be used in pregnant or lactating bitches, since its safety pertaining to these conditions is not known. Though early investigations did not identify any significant risks to dogs receiving treatment with Rimadyl, mild symptoms including vomiting, diarrhea, change in appetite, lethargy, behavioral changes and constipation were observed in a low percentage of dogs receiving either Rimadyl or the placebo. Clinical use of Rimadyl among a wider population has identified additional indications of drug intolerance within certain individual dogs including but not limited to jaundice, seizures, urinary tract disorders, loss of fur, rash, and swelling. These findings suggest that some individual dogs may be more predisposed to adverse reactions to Rimadyl than others.
Of particular noteworthiness to owners of Labrador Retrievers are the reports of hepatic (liver) toxicity occurring with greater frequency in Labs than in any other breed. This increase in occurrence may simply be due to the fact that as a breed, the Labrador Retriever ranks most prevalent among dogs. Additionally, hip dysplasia and other bone disorders occur with high frequency within the breed making them likely candidates for Rimadyl treatment. In the absence of knowing the total number of Labs taking Rimadyl and only having information pertaining to the number of Labs with toxic reactions, it is impossible to conclude if the breed does, indeed, run a higher risk for Rimadyl complications compared to any other breed. Alternatively, however, the fact that the breed is represented prevalently in the group which experienced hepatic complications and less frequently in other groups including those which experienced renal (kidney) toxicity, neurologic disorders, etc. suggests that the breed may, indeed, have less hepatic tolerance for the drug. Because it is currently unknown what factors may contribute to predispose certain Labradors to hepatic toxicity, it is recommended that Labradors administered Rimadyl be carefully observed for early signs of drug intolerance.
In general, one likely predisposing factor to complications associated with Rimadyl, may be underlying health conditions in older dogs. As with any drug, however, even some individual dogs in otherwise good health may experience severe reactions to treatment. Therefore, if your dog is taking Rimadyl, he should be monitored for any adverse symptoms.
Hyperactivity, Restlessness, or Aggressiveness
In addition to the above symptoms:
When symptoms occur, immediately discontinue Rimadyl treatment and contact your veterinarian for advice or to begin supportive therapy to counteract effects of drug toxicity, depending on severity of symptoms. In most cases of Rimadyl toxicity, discontinuing treatment and providing prompt follow-up care results in recovery, however, in cases of toxicity in which treatment was delayed, chronic liver disease and fatalities have resulted.
Pelletier JP, Lajeunesse D, Jovanovic DV, Lascau-Coman V, Jolicoeur FC, Hilal G, Fernandes JC, Martel-Pelletier J. Carprofen simultaneously reduces progression of morphological changes in cartilage and subchondral bone in experimental dog osteoarthritis. J Rheumatol 2000 Dec;27(12):2893-902
Reese CJ, Trotter EJ, Short CE, Erb HN, Barlow LL. Assessing the efficacy of perioperative carprofen administration in dogs undergoing surgical repair of a ruptured cranial cruciate ligament. J Am Anim Hosp Assoc 2000 Sep-Oct;36(5):448-55
Ko JC, Miyabiyashi T, Mandsager RE, Heaton-Jones TG, Mauragis DF. Renal effects of carprofen administered to healthy dogs anesthetized with propofol and isoflurane. J Am Vet Med Assoc 2000 Aug 1;217(3):346-9
E, Pibarot P, Dupuis J, Blais D. Comparison of ketoprofen and carprofen administered prior
to orthopedic surgery for control of
postoperative pain in dogs. J Am Vet Med Assoc 1999 Oct 15;215(8):1105-10
Forsyth SF, Guilford WG, Haslett SJ, Godfrey J. Endoscopy of the gastroduodenal mucosa after carprofen, meloxicam and ketoprofen administration in dogs. J Small Anim Pract 1998 Sep;39(9):421-4
MacPhail CM, Lappin MR, Meyer DJ, Smith SG, Webster CR, Armstrong PJ. Hepatocellular toxicosis associated with administration of carprofen in 21 dogs. J Am Vet Med Assoc 1998 Jun 15;212(12):1895-901