Companion Animal Product & Promotions Guide

DOSAGE AND ADMINISTRATION: Always provide Client Information Sheet with prescription. Carefully consider the potential benefits and risk of Rimadyl and other treatment options before deciding to use Rimadyl. 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. Rimadyl caplets and tablets are scored and dosage should be calculated in half-tablet increments. Tablets can be halved by placing the tablet on a hard surface and pressing down on both sides of the score. Rimadyl chewable tablets are palatable and willingly consumed by most dogs when offered by the owner. Therefore, they may be fed by hand or placed on food. Care should be taken to ensure that the dog consumes the complete dose. The recommended dosage for subcutaneous administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as either 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For control of post-operative pain, administer approximately 2 hours before the procedure. PALATABILITY: A controlled palatability study was conducted which demonstrated that Rimadyl chewable tablets were readily accepted and consumed on first offering by a majority of dogs. EFFECTIVENESS: Confirmation of the effectiveness of Rimadyl for the relief of pain and inflammation associated with osteoarthritis, and for the control of postoperative pain associated with soft tissue and orthopedic surgeries, was demonstrated in placebo-controlled, masked studies examining the anti-inflammatory and analgesic effectiveness of Rimadyl chewable tablets, caplets and injectable in various breeds of dogs. Separate placebo-controlled, masked, multicenter field studies confirmed the anti-inflammatory and analgesic effectiveness of Rimadyl caplets when dosed at 2 mg/lb once daily or when divided and administered at 1 mg/lb twice daily. In these two field studies, dogs diagnosed with osteoarthritis showed statistically significant overall improvement based on lameness evaluations by the veterinarian and owner observations when administered Rimadyl at labeled doses. Based upon the blood level comparison between subcutaneous and oral administration, Rimadyl effectiveness for osteoarthritis after dorsoscapular subcutaneous and oral administration should be similar, although there may be a slight delay in the onset of relief after subcutaneous injection. Separate placebo-controlled, masked, multicenter field studies confirmed the effectiveness of Rimadyl caplets and injectable for the control of postoperative pain when dosed at 2 mg/lb once daily in various breeds of dogs. In these studies, dogs presented for ovariohysterectomy, cruciate repair and aural surgeries were administered Rimadyl preoperatively and for a maximum of 3 days (soft tissue) or 4 days (orthopedic) postoperatively. In general, dogs administered Rimadyl showed statistically significant reduction in pain scores compared to controls. ANIMAL SAFETY: Laboratory studies in unanesthetized dogs and clinical field studies have demonstrated that Rimadyl is well tolerated in dogs after oral administration. In target animal safety studies, Rimadyl was administered orally to healthy Beagle dogs at 1, 3, and 5 mg/lb twice daily (1, 3 and 5 times the recommended total daily dose) for 42 consecutive days with no significant adverse reactions. Serum albumin for a single female dog receiving 5 mg/lb twice daily decreased to 2.1 g/dL after 2 weeks of treatment, returned to the pre-treatment value (2.6 g/dL) after 4 weeks of treatment, and was 2.3 g/dL at the final 6-week evaluation. Over the 6-week treatment period, black or bloody stools were observed in 1 dog (1 incident) treated with 1 mg/lb twice daily and in 1 dog (2 incidents) treated with 3 mg/lb twice daily. Redness of the colonic mucosa was observed in 1 male that received 3 mg/lb twice daily. Two of 8 dogs receiving 10 mg/lb orally twice daily (10 times the recommended total daily dose) for 14 days exhibited hypoalbuminemia. The mean albumin level in the dogs receiving this dose was lower (2.38 g/dL) than each of 2 placebo control groups (2.88 and 2.93 g/dL, respectively). Three incidents of black or bloody stool were observed in 1 dog. Five of 8 dogs exhibited reddened areas of duodenal mucosa on gross pathologic examination. Histologic examination of these areas revealed no evidence of ulceration, but did show minimal congestion of the lamina propria in 2 of the 5 dogs. In separate safety studies lasting 13 and 52 weeks, respectively, dogs were administered orally up to 11.4 mg/lb/day (5.7 times the recommended total daily dose of 2 mg/lb) of carprofen. In both studies, the drug was well tolerated clinically by all of the animals. No gross or histologic changes were seen in any of the treated animals. In both studies, dogs receiving the highest doses had average increases in serum L-alanine aminotransferase (ALT) of approximately 20 IU. In the 52-week study, minor dermatologic changes occurred in dogs in each of the treatment groups but not in the control dogs. The changes were described as slight redness or rash and were diagnosed as non-specific dermatitis. The possibility exists that these mild lesions were treatment related, but no dose relationship was observed. Clinical field studies were conducted with 549 dogs of different breeds at the recommended oral doses for 14 days (297 dogs were included in a study evaluating 1 mg/lb twice daily and 252 dogs were included in a separate study evaluating 2 mg/lb once daily). In both studies the drug was clinically well tolerated and the incidence of clinical adverse reactions for Rimadyl-treated animals was no higher than placebo-treated animals (placebo contained inactive ingredients found in Rimadyl). For animals receiving 1 mg/lb twice daily, the mean post-treatment serum ALT values were 11 IU greater and 9 IU less than pre-treatment values for dogs receiving Rimadyl and placebo, respectively. Differences were not statistically significant. For animals receiving 2 mg/lb once daily, the mean post-treatment serum ALT values were 4.5 IU greater and 0.9 IU less than pre-treatment values for dogs receiving Rimadyl and placebo, respectively. In the latter study, 3 Rimadyl-treated dogs developed a 3-fold or greater increase in (ALT) and/or (AST) during the course of therapy. One placebo-treated dog had a greater than 2-fold increase in ALT. None of these animals showed clinical signs associated with laboratory value changes. Changes in the clinical laboratory values (hematology and clinical chemistry) were not considered clinically significant. The 1 mg/lb twice daily course of therapy was repeated as needed at 2-week intervals in 244 dogs, some for as long as 5 years. Clinical field studies were conducted in 297 dogs of different breeds undergoing orthopedic or soft tissue surgery. Dogs were administered 2 mg/lb of Rimadyl 2 hours prior to surgery then once daily, as needed for 2 days (soft tissue surgery) or 3 days (orthopedic surgery). Rimadyl was well tolerated when used in conjunction with a variety of anesthetic-related drugs. The type and severity of abnormal health observation in Rimadyl- and placebo-treated animals were approximately equal and few in number (see Adverse Reactions). The most frequent abnormal health observation was vomiting and was observed at approximately the same frequency in Rimadyl- and placebo-treated animals. Changes in clinicopathologic indices of hematopoietic, renal, hepatic, and clotting function were not clinically significant. The mean post- treatment serum ALT values were 7.3 IU and 2.5 IU less than pre-treatment values for dogs receiving Rimadyl and placebo, respectively. The mean post-treatment AST values were 3.1 IU less for dogs receiving Rimadyl and 0.2 IU greater for dogs receiving placebo. Clinical field studies on the use of Rimadyl Injectable were conducted on 331 dogs undergoing orthopedic or soft tissue surgery. Dogs were administered 2 mg/lb of Rimadyl subcutaneously 2 hours prior to surgery and once daily thereafter, as needed, for 2 days (soft tissue surgery) or 3 days (orthopedic surgery). Rimadyl was well tolerated when used in conjunction with a variety of anesthetic-related drugs. The type and severity of abnormal health observations in Rimadyl- and placebo-treated animals were approximately equal and few in number (see Adverse Reactions). The most frequent abnormal health observation was vomiting and was observed at approximately the same frequency in Rimadyl- and placebo-treated animals. Changes in clinico- pathologic indices of hematopoietic, renal, hepatic, and clotting function were not clinically significant. The mean post-treatment serum ALT values were 8.4 IU and 7.0 IU less than pre-treatment values for dogs receiving Rimadyl and placebo, respectively. The mean post-treatment AST values were 1.5 IU and 0.7 IU greater for dogs receiving Rimadyl and placebo, respectively. Swelling and warmth were associated with the injection site after subcutaneous administration of Rimadyl Injectable. These findings were not clinically significant. Long term use of the injectable has not been studied. STORAGE: Store tablets at controlled room temperature 15°–30°C (59°–86°F). Store injectable under refrigeration 2°–8°C (36°–46°F). Once broached, product may be stored at temperatures up to 25°C (77°F) for 28 days. HOW SUPPLIED: Rimadyl caplets and chewable tablets are scored, and contain 25 mg, 75 mg, or 100 mg of carprofen per caplet or tablet. Each caplet size is packaged in bottles containing 30, 60, or 180 caplets, or blister packs containing 4 caplets. Each chewable tablet size is packaged in bottles containing 7, 30, 60, or 180 tablets. Rimadyl Injectable is supplied in 20-mL, amber, glass, sterile, multi-dose vials. REFERENCES: 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, p. 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 NSAIDs 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 nonste roi dal 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 E 2 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 Immuno pharma cology 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. Veter inary 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 Safety Data Sheet (SDS) call 1-888-963-8471. To report adverse reactions call Zoetis Inc. at 1-888-963-8471. Approved by FDA under NADA #141-053, NADA #141-111, NADA #141-199 Distributed by: Zoetis Inc. Kalamazoo, MI 49007 Based on Rimadyl Caplets PI 40028070, Revised May 2019; Rimadyl Chewable Tablets PI 40026875, Revised April 2019; and Rimadyl Sterile Injectable Solution PI 4019448, Revised March 2019.

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