Novox

Carprofen is a non-narcotic, non-steroidal anti-inflammatory agent with characteristic analgesic and antipyretic activity approximately equipotent to indomethacin in animal models.1

The mechanism of action of carprofen, like that of other NSAlDs, is believed to be associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals.2

The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. Inhibition of COX-l is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity. The specificity of a particular NSAID for COX-2 versus COX-1 may vary from species to species.3 In an in vitro study using canine cell cultures, carprofen demonstrated selective inhibition of COX-2 versus COX-1.4 Clinical relevance of these data has not been shown. Carprofen has also been shown to inhibit the release of several prostaglandins in two inflammatory cell systems: rat polymorphonuclear leukocytes (PMN) and human rheumatoid synovial cells, indicating inhibition of acute (PMN system) and chronic (synovial cell system) inflammatory reactions.1 Several studies have demonstrated that carprofen has modulatory effects on both humoral and cellular immune responses.5-9 Data also indicate that carprofen inhibits the production of osteoclast-activating factor (OAF), PGE1, and PGE2 by its inhibitory effects on prostaglandin biosynthesis.1

Based upon comparison with data obtained from intravenous administration, carprofen is rapidly and nearly completely absorbed (more than 90% bioavailable) when administered orally.l0 Peak blood plasma concentrations are achieved in 1-3 hours after oral administration of 1, 5, and 25 mg/kg to dogs. The mean terminal half-life of carprofen is approximately 8 hours (range 4.5-9.8 hours) after single oral doses varying from 1-35 mg/kg of body weight. After a 100 mg single intravenous bolus dose, the mean elimination half-life was approximately 11.7 hours in the dog. Carprofen is more than 99% bound to plasma protein and exhibits a very small volume of distribution.

Carprofen is eliminated in the dog primarily by biotransformation in the liver followed by rapid excretion of the resulting metabolites (the ester glucuronide of carprofen and the ether glucuronides of 2 phenolic metabolites, 7-hydroxy-carprofen and 8-hydroxy carprofen) in the feces (70-80%) and urine (10-20%). Some enterohepatic circulation of the drug is observed.

Carprofen is indicated for the relief of pain and inflammation associated with osteoarthritis and for the control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Keep out of reach of children. Not for human use. Consult a physician in cases of accidental ingestion by humans. For use in dogs only. Do not use in cats.

All dogs should undergo a thorough history and physical examination before initiation of NSAID therapy. Appropriate laboratory tests to establish hematological and serum biochemical baseline data prior to, and periodically during, administration of any NSAID should be considered. Owners should be advised to observe for signs of potential drug toxicity (see Information for Dog Owners, Adverse Reactions, Animal Safety and Post-Approval Experience).

Always provide Client Information Sheet with prescription. Carefully consider the potential benefits and risk of Novox and other treatment options before deciding to use Novox. Use the lowest effective dose for the shortest duration consistent with individual response. The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure. Caplets are scored and dosage should be calculated in half-caplet increments.

1. Baruth H, et al: In Anti-Inflammatory and Anti-Rheumatic Drugs, Vol. II, Newer Anti-Inflammatory Drugs, Rainsford KD, ed. CRC Press, Boca Raton, pp. 33-47, 1986.
2. Vane JR, Botting RM: Mechanism of action of anti-inflammatory drugs. Scand J Rheumatol 25:102, pp. 9-21.
3. Grossman CJ, Wiseman J, Lucas FS, et al: Inhibition of constitutive and inducible cyclooxygenase activity in human platelets and mononuclear cells by NSAlDs and COX-2 inhibitors. Inflammation Research 44:253-257, 1995.
4. Ricketts AP, Lundy KM, Seibel SB: Evaluation of selective inhibition of canine cyclooxygenase 1 and 2 by carprofen and other nonsteroidal anti-inflammatory drugs. Am J Vet Res 59:11, pp. 1441-1446, November 1998.
5. Ceuppens JL, et al: Non-steroidal anti-inflammatory agents inhibit the synthesis of IgM rheumatoid factor in vitro. Lancet 1:528, 1982.
6. Ceuppens JL, et al: Endogenous prostaglandin E2 enhances polyclonal immunoglobulin production by ionically inhibiting T suppressor cell activity. Cell Immunol 70:41, 1982.
7. Schleimer RP, et al: The effects of prostaglandin synthesis inhibition on the immune response. Immunopharmacology 3:205, 1981.
8. Leung KH, et al: Modulation of the development of cell mediated immunity: possible roles of the products of cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Int J Immunopharmacology 4:195, 1982.
9. Veit BC: Immunoregulatory activity of cultured-induced suppressor macrophages. Cell Immunol 72:14, 1982.
10. Schmitt M, et al: Biopharmaceutical evaluation of carprofen following single intravenous, oral, and rectal doses in dogs. Biopharm Drug Dispos 11(7):585-94,1990.
11. Kore AM: Toxicology of nonsteroidal anti-inflammatory drugs. Veterinary Clinics of North America, Small Animal Practice 20, March 1990.
12. Binns SH: Pathogenesis and pathophysiology of ischemic injury in cases of acute renal failure. Compend for Cont Ed 16:1, January 1994.
13. Boothe DM: Prostaglandins: Physiology and clinical implications. Compend for Cont Ed 6:11, November 1984.
14. Rubin SI: Nonsteroidal anti-inflammatory drugs, prostaglandins, and the kidney. JAVMA 188:9, May 1986.
15. Ko CH, Lange DN, Mandsager RE, et al: Effects of butorphanol and carprofen on the minimal alveolar concentration of isoflurane in dogs. JAVMA 217:1025-1028, 2000.

For a copy of the Material Safety Data Sheet (MSDS) or to report adverse reactions call Vedco, Inc. at 1-888-708-3326.

ANADA 200-498, Approved by FDA

Distributed by:
Vedco, Inc.
St. Joseph, MO 64507

®Novox is a registered trademark of Vedco, Inc.

VEDCO

Dog Owner Information about Novox® CAPLETS (carprofen) for Osteoarthritis and Post-Surgical Pain Generic name: carprofen (”car-prô-fen”)

This summary contains important information about Novox® Caplets. You should read this information before you start giving your dog Novox® Caplets and review it each time the prescription is refilled. This sheet is provided only as a summary and does not take the place of instructions from your veterinarian. Talk to your veterinarian if you do not understand any of this information or if you want to know more about Novox® Caplets.

What is Novox® Caplets?

Novox® Caplets is a nonsteroidal anti-inflammatory drug (NSAID) that is used to reduce pain and inflammation (soreness) due to osteoarthritis and pain following surgery in dogs. Novox® Caplets is a prescription drug for dogs. It is available as a caplet and is given to dogs by mouth. Osteoarthritis (OA) is a painful condition caused by "wear and tear" of cartilage and other parts of the joints that may result in the following changes or signs in your dog:

• Limping or lameness
• Decreased activity or exercise (reluctance to stand, climb stairs, jump or run, or difficulty in performing these activities)
• Stiffness or decreased movement of joints

To control surgical pain (e.g. for surgeries such as spays, ear procedures or orthopedic repairs) your veterinarian may administer Novox® Caplets before the procedure and recommend that your dog be treated for several days after going home.

What kind of results can I expect when my dog is on Novox® Caplets?

While Novox® Caplets is not a cure for osteoarthritis, it can relieve the pain and inflammation of OA and improve your dog's mobility.

• Response varies from dog to dog but can be quite dramatic.
• In most dogs, improvement can be seen in a matter of days.
• If Novox® Caplets is discontinued or not given as directed, your dog's pain and inflammation may come back.

Who should not take Novox® Caplets?

Your dog should not be given Novox® Caplets if he/she:

• Has had an allergic reaction to carprofen, the active ingredient of Novox® Caplets.
• Has had an allergic reaction to aspirin or other NSAIDs (for example deracoxib, etodalac, firocoxib, meloxicam, phenylbutazone or tepoxalin) such as hives, facial swelling, or red or itchy skin.

Novox® Caplets should be given to dogs only. Cats should not be given Novox® Caplets. Call your veterinarian immediately if your cat receives Novox® Caplets. People should not take Novox® Caplets. Keep Novox® Caplets and all medicines out of reach of children. Call your physician immediately if you accidentally take Novox® Caplets.

How to give Novox® Caplets to your dog.

Novox® Caplets should be given according to your veterinarian's instructions. Your veterinarian will tell you what amount of Novox® Caplets is right for your dog and for how long it should be given. Novox® Caplets should be given by mouth and may be given with or without food.

What to tell/ask your veterinarian before giving Novox® Caplets.

Talk to your veterinarian about:

• The signs of OA you have observed (for example limping, stiffness).
• The importance of weight control and exercise in the management of OA.
• What tests might be done before Novox® Caplets is prescribed.
• How often your dog may need to be examined by your veterinarian.
• The risks and benefits of using Novox® Caplets.

Tell your veterinarian if your dog has ever had the following medical problems:

• Experienced side effects from Novox® Caplets or other NSAIDs, such as aspirin
• Digestive upset (vomiting and/or diarrhea)
• Liver disease
• Kidney disease
• A bleeding disorder (for example, Von Willebrand's disease)

Tell your veterinarian about:

• Any other medical problems or allergies that your dog has now or has had.
• All medicines that you are giving your dog or plan to give your dog, including those you can get without a prescription.

Tell your veterinarian if your dog is:

• Pregnant, nursing or if you plan to breed your dog.

What are the possible side effects that may occur in my dog during Novox® Caplets therapy?

Novox® Caplets, like other drugs, may cause some side effects. Serious but rare side effects have been reported in dogs taking NSAIDs, including Novox® Caplets. Serious side effects can occur with or without warning and in rare situations result in death.

The most common NSAID-related side effects generally involve the stomach (such as bleeding ulcers), and liver or kidney problems. Look for the following side effects that can indicate your dog may be having a problem with Novox® Caplets or may have another medical problem:

• Decrease or increase in appetite
• Vomiting
• Change in bowel movements (such as diarrhea, or black, tarry or bloody stools)
• Change in behavior (such as decreased or increased activity level, incoordination, seizure or aggression)
• Yellowing of gums, skin, or whites of the eyes (jaundice)
• Change in drinking habits (frequency, amount consumed)
• Change in urination habits (frequency, color, or smell)
• Change in skin (redness, scabs, or scratching)

It is important to stop therapy and contact your veterinarian immediately if you think your dog has a medical problem or side effect from Novox® Caplets therapy. If you have additional questions about possible side effects, talk to your veterinarian.

Can Novox® Caplets be given with other medicines?

Novox® Caplets should not be given with other NSAIDs (for example aspirin, deracoxib, etodalac, firocoxib, meloxicam, tepoxalin) or steroids (for example cortisone, dexamethasone, prednisone, triamcinolone). Tell your veterinarian about all medicines you have given your dog in the past, and any medicines that you are planning to give with Novox® Caplets. This should include other medicines that you can get without a prescription. Your veterinarian may want to check that all of your dog's medicines can be given together.

What do I do in case my dog eats more than the prescribed amount of Novox® Caplets?

Contact your veterinarian immediately if your dog eats more than the prescribed amount of Novox® Caplets.

What else should I know about Novox® Caplets?

This sheet provides a summary of information about Novox® Caplets. If you have any questions or concerns about Novox® Caplets, or osteoarthritis, or postoperative pain, talk to your veterinarian.

As with all prescribed medicines, Novox® Caplets should only be given to the dog for which it was prescribed. It should be given to your dog only for the condition for which it was prescribed.

It is important to periodically discuss your dog's response to Novox® Caplets at regular check ups. Your veterinarian will best determine if your dog is responding as expected and if your dog should continue receiving Novox® Caplets.

To report a suspected adverse reaction call Vedco, Inc. at 1-888-708-3326.

Made in the UK
Manufactured By:
Norbrook Laboratories Limited
Newry, Northern Ireland

Distributed by:
Vedco, Inc.
St. Joseph, MO 64507

® Novox is a registered trademark of Vedco, Inc.

001762I02

VEDCO

NDC 50989-245-86
Novox® CAPLETS
(carprofen)
Non-steroidal anti-inflammatory drug
For oral use in dogs only
100 MG
180 CAPLETS
Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.
VEDCO
ANADA #200-498, Approved by FDA