VETPROFEN- carprofen_tablet

CLINICAL PHARMACOLOGY
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 NSAIDs, is believed to be associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals. 2 3 in vitro 4 1 Several studies have demonstrated that carprofen has modulatory effects on both humoral and cellular immune responses. 5-9 1 2 1 Based upon comparison with data obtained from intravenous administration, carprofen is rapidly and nearly completely absorbed (more than 90% bioavailable) when administered orally. 10 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.
EFFECTIVENESS
Confirmation of the effectiveness of carprofen 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 5 placebo-controlled, masked studies examining the antiinflammatory and analgesic effectiveness of carprofen caplets in various breeds of dogs. Separate placebo-controlled, masked, multicenter field studies confirmed the anti-inflammatory and analgesic effectiveness of carprofen 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 carprofen at labeled doses. Separate placebo-controlled, masked, multicenter field studies confirmed the effectiveness of carprofen caplets 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 carprofen preoperatively and for a maximum of 3 days (soft tissue) or 4 days (orthopedic) postoperatively. In general, dogs administered carprofen showed statistically significant improvement in pain scores compared to controls.

Vetprofen 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.

Always provide Client Information Sheet with prescription. 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.

ADVERSE REACTIONS
During investigational studies of osteoarthritis with twice daily administration of 1 mg/lb, no clinically significant adverse reactions were reported. Some clinical signs were observed during field studies (n=297) which were similar for carprofen- and placebo-treated dogs. Incidences of the following were observed in both groups: vomiting (4%), diarrhea (4%), changes in appetite (3%), lethargy (1. 4%), behavioral changes (1%), and constipation (0. The product vehicle served as control. There were no serious adverse events reported during clinical field studies of osteoarthritis with once daily administration of 2 mg/lb. The following categories of abnormal health observations were reported. Percentage of Dogs with Abnormal Health Observations Reported in Osteoarthritis Field Study (2 mg/lb once daily) Observation Carprofen (n=129) Placebo (n=132) Clinical pathology parameters listed represent reports of increases from pre-treatment values; medical judgment is necessary to determine clinical relevance. Inappetance 1. 5 Vomiting 3. 8 Diarrhea/Soft stool 3. 5 Behavior change 0. 8 Dermatitis 0. 8 ---- SAP increase 7. 3 ALT increase 5. 5 AST increase 2. 8 BUN increase 3. 5 Bilirubinuria 16. 1 Ketonuria 14. 1 During investigational studies of surgical pain for the caplet formulation, no clinically significant adverse reactions were reported. Percentage of Dogs with Abnormal Health Observations Reported in Surgical Pain Field Studies with Caplets (2 mg/lb once daily) Observation A single dog may have experienced more than one occurrence of an event Carprofen (n=148) Placebo (n=149) Vomiting 10. 4 Diarrhea/Soft stool 6. 0 Ocular disease 2. 7 0 Inappetance 1. 4 0 Dermatitis/skin lesion 2. 3 Dysrhythmia 0. 7 0 Apnea 1. 4 0 Oral/periodontal disease 1. 4 0 Pyrexia 0. 3 Urinary tract disease 1. 3 Wound drainage 1. 4 0 Although not all adverse reactions are reported, the following adverse reactions are based on voluntary post-approval adverse drug experience reporting. The categories of adverse reactions are listed in decreasing order of frequency by body system. Gastrointestinal: Vomiting, diarrhea, constipation, inappetence, melena, hematemesis, gastrointestinal ulceration, gastrointestinal bleeding, pancreatitis. Hepatic: Inappetence, vomiting, jaundice, acute hepatic toxicity, hepatic enzyme elevation, abnormal liver function test(s), hyperbilirubinemia, bilirubinuria, hypoalbuminemia. Approximately one-fourth of hepatic reports were in Labrador Retrievers. Neurologic: Ataxia, paresis, paralysis, seizures, vestibular signs, disorientation. Urinary: Hematuria, polyuria, polydipsia, urinary incontinence, urinary tract infection, azotemia, acute renal failure, tubular abnormalities including acute tubular necrosis, renal tubular acidosis, glucosuria. Behavioral: Sedation, lethargy, hyperactivity, restlessness, aggressiveness. Hematologic: Immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, blood loss anemia, epistaxis. Dermatologic: Pruritus, increased shedding, alopecia, pyotraumatic moist dermatitis (hot spots), necrotizing panniculitis/vasculitis, ventral ecchymosis. Immunologic or hypersensitivity: Facial swelling, hives, erythema. In rare situations, death has been associated with some of the adverse reactions listed above. To report a suspected adverse reaction call 1-800-835-9496.
Post-Approval Experience
Although not all adverse reactions are reported, the following adverse reactions are based on voluntary post-approval adverse drug experience reporting. The categories of adverse reactions are listed in decreasing order of frequency by body system. Gastrointestinal: Vomiting, diarrhea, constipation, inappetence, melena, hematemesis, gastrointestinal ulceration, gastrointestinal bleeding, pancreatitis. Hepatic: Inappetence, vomiting, jaundice, acute hepatic toxicity, hepatic enzyme elevation, abnormal liver function test(s), hyperbilirubinemia, bilirubinuria, hypoalbuminemia. Approximately one-fourth of hepatic reports were in Labrador Retrievers. Neurologic: Ataxia, paresis, paralysis, seizures, vestibular signs, disorientation. Urinary: Hematuria, polyuria, polydipsia, urinary incontinence, urinary tract infection, azotemia, acute renal failure, tubular abnormalities including acute tubular necrosis, renal tubular acidosis, glucosuria. Behavioral: Sedation, lethargy, hyperactivity, restlessness, aggressiveness. Hematologic: Immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, blood loss anemia, epistaxis. Dermatologic: Pruritus, increased shedding, alopecia, pyotraumatic moist dermatitis (hot spots), necrotizing panniculitis/vasculitis, ventral ecchymosis. Immunologic or hypersensitivity: Facial swelling, hives, erythema. In rare situations, death has been associated with some of the adverse reactions listed above. To report a suspected adverse reaction call 1-800-835-9496.

Vetprofen should not be used in dogs exhibiting previous hypersensitivity to carprofen.

Store at controlled room temperature 15°C - 30°C (59°F - 86°F).

WARNINGS
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 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 Post-Approval Experience
ANIMAL SAFETY
Laboratory studies in unanesthetized dogs and clinical field studies have demonstrated that carprofen is well tolerated in dogs after oral administration. In target animal safety studies, carprofen 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 nonspecific 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 carprofen- treated animals was no higher than placebo-treated animals (placebo contained inactive ingredients found in carprofen). 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 carprofen 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 carprofen and placebo, respectively. In the latter study, 3 carprofen- 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 carprofen two hours prior to surgery then once daily, as needed for 2 days (soft tissue surgery) or 3 days (orthopedic surgery). Carprofen was well tolerated when used in conjunction with a variety of anesthetic-related drugs. The type and severity of abnormal health observations in carprofen-and placebo-treated animals were approximately equal and few in number (see Adverse Reactions
REFERENCES
Baruth H, et al: Vane JR, Botting RM: Mechanism of action of anti-inflammatory drugs. Scand J Rheumatol Grossman CJ, Wiseman J, Lucas FS, et al: Inflammation Research 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 Ceuppens JL, et al: in vitro. Lancet Ceuppens JL, et al: 2 Cell Immunol Schleimer RP, et al: Immunopharmacology Leung KH, et al: Int J Immunopharmacology Veit BC: Immunoregulatory activity of cultured-induced suppressor macrophages. Cell Immunol Schmitt M, et al: Biopharm Drug Dispos Kore AM: Toxicology of nonsteriodal anti-inflammatory drugs. Veterinary Clinics of North America, Small Animal Practice Binns SH: Pathogenesis and pathophysiology of ischemic injury in cases of acute renal failure. Compend for Cont Ed Boothe DM: Prostaglandins: Physiology and clinical implications. Compend for Cont Ed Rubin SI: Nonsteroidal anti-inflammatory drugs, prostaglandins, and the kidney. JAVMA Ko CH, Lange DN, Mandsager RE, et al: JAVMA
PATIENT PACKAGE INSERT
Dog Owner Information about trademark Vetprofen trademark This summary contains important information about Vetprofen. You should read this information before you start giving your dog Vetprofen 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 Vetprofen. What is Vetprofen? Vetprofen 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. Vetprofen 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 Vetprofen 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 Vetprofen? While Vetprofen 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 Vetprofen is discontinued or not given as directed, your dog''s pain and inflammation may come back. Who should not take Vetprofen? Your dog should not be given Vetprofen if he/she: Has had an allergic reaction to carprofen, the active ingredient of Vetprofen. Has had an allergic reaction to aspirin or other NSAIDs (for example deracoxib, etodolac, firocoxib, meloxicam, phenylbutazone or tepoxalin) such as hives, facial swelling, or red or itchy skin. Vetprofen should be given to dogs only. Cats should not be given Vetprofen. Call your veterinarian immediately if your cat receives Vetprofen. People should not take Vetprofen. Keep Vetprofen and all medicines out of reach of children. Call your physician immediately if you accidentally take Vetprofen. How to give Vetprofen to your dog Vetprofen should be given according to your veterinarian''s instructions. Your veterinarian will tell you what amount of Vetprofen is right for your dog and for how long it should be given. Vetprofen should be given by mouth and may be given with or without food. What to tell/ask your veterinarian before giving Vetprofen 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 Vetprofen is prescribed. How often your dog may need to be examined by your veterinarian. The risks and benefits of using Vetprofen. Tell your veterinarian if your dog has ever had the following medical problems: Experienced side effects from Vetprofen 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 Vetprofen therapy? Vetprofen, like other drugs, may cause some side effects. Serious but rare side effects have been reported in dogs taking NSAIDs, including carprofen. 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 Vetprofen 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 Vetprofen therapy. If you have additional questions about possible side effects, talk to your veterinarian. Can Vetprofen be given with other medicines? Vetprofen should not be given with other NSAIDs (for example, aspirin, deracoxib, etodolac, 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 Vetprofen. 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 Vetprofen? Contact your veterinarian immediately if your dog eats more than the prescribed amount of Vetprofen. What else should I know about Vetprofen? This sheet provides a summary of information about Vetprofen. If you have any questions or concerns about Vetprofen, or osteoarthritis, or postoperative pain, talk to your veterinarian. As with all prescribed medicines, Vetprofen 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 Vetprofen at regular check ups. Your veterinarian will best determine if your dog is responding as expected and if your dog should continue receiving Vetprofen. To report a suspected adverse reaction call 1-800-835-9496 Issued July 2007 Manufactured by: Belcher Pharmaceuticals, Inc. Distributed by: Vétoquinol U.S.A., Inc.

Vetoquinol USA Inc

VETPROFEN- carprofen_tablet Product manual source documgent