Parameter
| Value |
| Tmaxa | 2 hours |
| Oral Bioavailability (F)a | > 90% at 2 mg/kg |
| Terminal elimination half-lifeb | 3 hours at 2-3 mg/kg
19 hours at 20 mg/kg |
| Systemic Clearance b | ~ 5 ml/kg/min at 2 mg/kg
~ 1.7 ml/kg/min at 20 mg/kg |
| Volume of Distributionc | ~ 1.5 L/kg |
| Protein binding d | > 90% |
a Values obtained following a single 2.35 mg/kg dose
b Estimates following IV administration of deracoxib as an aqueous solution
c Based upon a dose of 2 mg/kg of deracoxib
d Based upon in vitro plasma concentrations of 0.1, 0.3, 1.0, 3.0, 10.0 µg/ml
|
Animal Safety:
In a 6-month study, dogs were dosed with DERAMAXX® 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.
Palatability:
DERAMAXX tablets were evaluated for palatability in 100 client-owned dogs of a variety of breeds and sizes. Dogs received two doses of DERAMAXX® tablets, one on each of two consecutive days. DERAMAXX® tablets were accepted by 94% of dogs on the first day of dosing and by 92% of dogs on the second day of dosing.
Effectiveness:
DERAMAXX® tablets were evaluated in masked, placebo-controlled multi-site field studies involving client-owned animals to determine effectiveness.
Postoperative Orthopedic Pain and Inflammation Field Study:
In this study, 207 dogs admitted to veterinary hospitals for repair of a cranial cruciate injury were randomly administered DERAMAXX® tablets or a placebo. Drug administration started the evening before surgery and continued once daily for 6 days postoperatively. Effectiveness was evaluated in 119 dogs and safety was evaluated in 207 dogs. Statistically significant differences in favor of DERAMAXX® tablets were found for lameness at walk and trot, and pain on palpation values at all post-surgical time points. The results of this field study demonstrate that DERAMAXX® tablets, when administered daily for 7 days are effective for the control of postoperative pain and inflammation associated with orthopedic surgery.
Storage Conditions:
DERAMAXX® tablets should be stored at room temperature between 59° and 86°F (15-30°C).
Keep this and all medications out of reach of children.
