The use of concomitantly protein-bound drugs with deracoxib tablets has not been studied in dogs. Commonly used protein-bound drugs include cardiac, anticonvulsant and behavioral medications. The influence of concomitant drugs that may inhibit metabolism of deracoxib tablets has not been evaluated. Drug compatibility should be monitored in patients requiring adjunctive therapy. Consider appropriate washout times when switching from one NSAID to another or when switching from corticosteroid use to NSAID use.
In a 6-month study, dogs were dosed with deracoxib at 0, 2, 4, 6, 8 and 10 mg/kg with food once daily for 6 consecutive months. There were no abnormal feces, and no abnormal findings on clinical observations, food and water consumption, body weights, physical examinations, ophthalmoscopic evaluations, macroscopic pathological examinations, hematology, or buccal bleeding time. Urinalysis results showed hyposthenuria (specific gravity <1.005) and polyuria in one male and one female in the 6 mg/kg group after 6 months of treatment. After 6 months of treatment, the mean BUN values for dogs treated with 6, 8, or 10 mg/kg/day were 30.0, 35.3, and 48.2 mg/dL respectively. No effects were seen on any other clinical chemistry parameters, including other variables associated with renal physiology (serum creatinine, serum electrolytes, and urine sediment evaluation). Dose dependent focal renal tubular degeneration/regeneration was seen in some dogs treated at 6, 8, and 10 mg/kg/day. Focal renal papillary necrosis was seen in 3 dogs dosed at 10 mg/kg/day and in one dog dosed at 8 mg/kg/day. No renal lesions were seen at the label doses of 2 and 4 mg/kg/day. There was no evidence of gastrointestinal, hepatic, or hematopoietic pathology at any of the doses tested.
In a laboratory study, healthy young dogs were dosed with deracoxib tablets once daily, within 30 minutes of feeding, at doses of 0, 4, 6, 8, and 10 mg/kg body weight for 21 consecutive days. No adverse drug events were reported. There were no abnormal findings reported for clinical observations, food and water consumption, body weights, physical examinations, ophthalmic evaluations, organ weights, macroscopic pathologic evaluation, hematology, urinalyses, or buccal mucosal bleeding time. In the clinical chemistry results there was a statistically significant (p<0.0009) dose-dependent trend toward increased levels of blood urea nitrogen (BUN). Mean BUN values remained within historical normal limits at the label dose. No effects on other clinical chemistry values associated with renal function were reported. There was no evidence of renal, gastrointestinal, hepatic or biliary lesions noted during gross necropsy. Renal histopathology revealed trace amounts of tubular degeneration/regeneration in all dose groups including placebo, but no clear dose relationship could be determined. There was no histopathologic evidence of gastrointestinal, hepatic or biliary lesions.
In another study, micronized deracoxib in gelatin capsules was administered once daily to healthy young dogs at doses of 10, 25, 50, and 100 mg/kg body weight for periods up to 14 consecutive days. Food was withheld prior to dosing. Non-linear elimination kinetics occurred at all doses. At doses of 25, 50, and 100 mg/kg, reduced body weight, vomiting, and melena occurred. Necropsy revealed gross gastrointestinal lesions in dogs from all dose groups. The frequency and severity of the lesions increased with escalating doses. At 10 mg/kg, moderate diffuse congestion of gut associated lymphoid tissues (GALT) and erosions/ulcers in the jejunum occurred. At 100 mg/kg, all dogs exhibited gastric ulcers and erosions/ulcerations of the small intestines. There were no hepatic or renal lesions reported at any dose in this study.
In a 13-week study, deracoxib in gelatin capsules was administered to healthy dogs at doses of 0, 2, 4, and 8 mg/kg/day. No test-article related changes were identified in clinical observations, physical exams, or any of the other parameters measured. One dog in the 8 mg/kg dose group died from bacterial septicemia secondary to a renal abscess. The relationship between deracoxib administration and the renal abscess is not clear.
Effectiveness:
Deracoxib tablets were evaluated in masked, placebo-controlled multi-site field studies involving client-owned animals to determine effectiveness.
Osteoarthritis Pain and Inflammation Field Study:
Two hundred and nine (209) client-owned dogs with clinical and radiographic signs of osteoarthritis of at least one appendicular joint were enrolled in this study. A total of 194 dogs were included in the safety evaluation and a total of 181 dogs were included in the effectiveness evaluation. The effectiveness of deracoxib tablets in the control of pain and inflammation associated with osteoarthritis was demonstrated in a placebo-controlled, masked study evaluating the anti-inflammatory and analgesic effects of deracoxib tablets. Tablets were administered by the owner at approximately 1-2 mg/kg/day for forty-three (43) consecutive days.
In general, statistically significant (p< 0.05) differences in favor of deracoxib were seen for force plate parameters (vertical impulse area, peak vertical force) and owner evaluations (quality of life, lameness and overall level of activity).
The results of this field study demonstrate that deracoxib tablets, when administered at 1-2 mg/kg/day for 43 days, are effective for the control of pain and inflammation associated with osteoarthritis.