(for veterinary information only)

BRAND NAME: RIMADYL
(ZENECARP IN THE U.K.)

AVAILABLE IN    
25 mg, 75 mg & 100 mg
CAPLETS         
and INJECTABLE  

BACKGROUND

Carprofen is a member of the class of drugs known as NSAIDs (non-steroidal anti-inflammatory drugs), the same class as such common over-the-counter remedies as Advil (Ibuprofen), Aleve (Naproxen), Orudis (ketoprofen), and Aspirin.  The chief use for such drugs in the dog has been pain relief, usually joint pain or post-surgical pain relief.

The problem with this class of drugs has been unacceptable (even life-threatening) side effects. Problems have in the past been related to:

• Stomach ulceration - even perforation and rupture of the stomach can occur. This is not only painful but life-threatening.
   
• Platelet deactivation - platelets are the cells controlling the ability to clot blood and, as a general rule, it is preferable not to promote bleeding. We would prefer platelets to remain active and able to function should we need them.
   
• Decreased blood supply to the kidney - this could tip a borderline patient in to kidney failure.

The veterinary profession has been in need of an NSAID that could effectively relieve pain without the above risks. In 1997, Pfizer Animal Health released this medication for dogs in the U.S. as the answer to this need. This medication had been available in the U.K. since 1994 and has earned a reputation for effectiveness and safety.

This new plane of safety is made possible by new biochemical knowledge. The enzyme responsible for many inflammatory mediators is called cyclo-oxygenase-2 while another enzyme, cyclo-oxygenase-1, is responsible for producing important biochemicals needed to maintain normal blood supply to the kidneys and GI tract. It had been previously impossible to inhibit cyclo-oxygenase-2 without also inhibiting cyclo-oxygenase-1, hence the side effects of previous NSAIDS. Carprofen is what is called a selective cyclo-oxygenase-2 inhibitor. Carprofen does inhibit cyclo-oxygenase-1 slightly but, for the first time, it became possible to exert a different effect on each of these two enzymes.

HOW THIS MEDICATION IS USED

Carprofen is used in the treatment of pain either for short term or long term use. It takes 1-3 hours after oral administration for a dose of carprofen to reach its maximum effect. As of December 2001, Carprofen has been licensed for once a day use (ie the dose for the entire day can be given all at once).

Carprofen is approved only for canine use officially and dogs may safely take this medication long term with no ill effects.  Injectable carprofen, only available in the U.K., is commonly used for post-operative pain relief in the cat but only one or two doses are typically given. Do not use this medication in a cat without specific veterinary guidance.

SIDE EFFECTS

• There is an approximately one in 1000 chance of a dog on carprofen developing nausea, appetite loss, vomiting or diarrhea. If any of the above are noted, carprofen should be discontinued and the dog brought in for a liver enzyme blood test. In most cases, the reaction is minor and resolves with symptomatic relief, but it is important to rule out whether or not the patient has more than just a routine upset stomach (see below).
   
• The Hepatopathy Side Effect (usually occurs within the first 3 weeks of use)
  
  A carprofen reaction that has received special attention is hepatopathy, a type of liver disease. When carprofen was released in 1997, it had received its FDA approval based on 400 or so test dogs. Since 1997, carprofen has been used in 4 million dogs. With these larger numbers, a very rare syndrome (one in 5000 dogs) became evident. Symptoms include nausea, appetite loss, and/or diarrhea as well as marked elevations (3-4 times higher than the normal range) in liver enzymes measured in the blood.
  
  Dogs with this syndrome show improvement with support 5 - 10 days after discontinuing carprofen. It is important that carprofen be discontinued and the patient evaluated in the event of upset stomach signs in case of this syndrome. Even though this is a rare syndrome (one in 5000), it can become life-threatening if ignored.  Appetite loss or other intestinal signs do not necessarily indicate a hepatopathy but since they might, it is important not to ignore these signs should they occur.
  
  Initially, the Labrador Retriever appeared to be over-represented but this may actually reflect the overall popularity of the breed and/or their predisposition to musculo-skeletal problems requiring carprofen therapy.

The hepatopathy reaction usually occurs in the first 3 weeks
after starting carprofen but could theoretically occur later.

• Because carprofen inhibits cyclo-oxygenase-1 slightly, there could be potential for renal side effects in a patient depending truly on the edge of developing renal failure. Excess water consumption and urination would be evident in such a patient and possibly so would signs of upset stomach.
   
• Other rare side effects (one in 5000 or less) include: loss of balance, hyperactivity, depression, and aggression.

It is important to consider the rarity of one in 5000 side effects. In 1998, the adverse event rate overall was less than one in 500 dogs with simple upset stomach being the most common effect. Many exaggerated reports and rumors have surfaced on the internet and it is important to consider only confirmed and properly investigated information.

To read the most recent Pfizer Animal Health Technical Bulletin on Carprofen, click here:

www.pfizer.com/ah/rimadyl/tbull.html

INTERACTIONS WITH OTHER DRUGS

Drugs of the NSAID class should not be used concurrently as the potential for the aforementioned side effects increases. For similar reasons, NSAIDS should not be used in conjunction with corticosteroid hormones such as prednisone, dexamethasone etc.  Pfizer recommends a 2 - 3 day rest period when changing over to carprofen or to another NSAID from carprofen.  Aspirin poses an exception due to its strong platelet inactivating abilities so 10-14 days is recommened when switching to carprofen from apsirin. Allow at least one week between prednisone and carprofen.

If carprofen is used concurrently with phenobarbital, it is especially important that appropriate liver monitoring be performed. (Our hospital recommends bile acids testing every 6 months for dogs on phenobarbital.) These two drugs interact such that neither may work well if they are used together.

ACE inhibitors such as enalapril or captopril may not be as effective in the presence of carprofen. (ACE inhibitors are used in the treatment of hypertension or heart failure.) This is because ACE inhibitors depend on the dilation of blood vessels in the kidneys and such dilation can be interfered with by NSAIDs (though as discussed, carprofen as a COX-2 inhibitor is less apt to pose a problem than other NSAIDs might).

In 9% of all adverse reactions reported regarding carprofen,
concurrent use with corticosteroids was reported.

CONCERNS AND CAUTIONS

Carprofen is available as a chewable tablet which is highly palatable to animals. This increases the potential for accidental overdose should a pet gain access to a large amount of chewable tablets.  Keep chewable carprofen out of the reach of children and pets.

Carprofen has not been tested in pregnant or nursing females and thus is not recommended for use in such individuals.

Carprofen should not be used in dogs with pre-existing liver or kidney disease. In order to screen for pre-existing liver or kidney disease it is a good idea to run a blood chemistry panel prior to starting long term carprofen.

ANY DOG ON LONG TERM MEDICATION OF ANY KIND SHOULD
PROBABLY HAVE BLOOD CHEMISTRY RECHECKS EVERY 6 MONTHS.

Carprofen should not be used in patients with pre-existing GI ulcerations.

To read the product insert for Carprofen, click here:

arthritis.rimadyl.com/pi.html