Equine & Livestock

Approved by FDA under NADA # 141-458 Equioxx ® Tablets (firocoxib) 57mg Approved by FDA under NADA # 141-253 Equioxx ® Oral Paste for Horses (firocoxib) Human Warnings: Not for use in humans. Keep this and all medications out of the reach of children. Consult a physician in case of accidental ingestion by humans. Precautions: Horses should undergo a thorough history and physical examination before initiation of NSAID therapy. Appropriate laboratory tests should be conducted to establish hematological and serum biochemical baseline data before and periodically during administration of any NSAID. Clients should be advised to observe for signs of potential drug toxicity and be given a Client Information Sheet with each prescription. See Information for Owner or Person Treating Horse section of this package insert. Treatment with EQUIOX X should be terminated if signs such as inappetence, colic, abnormal feces, or lethargy are observed. As a class, cyclooxygenase inhibitory NSAIDs may be associated with gastrointestinal, renal, and hepatic toxicity. Sensitivity to drug-associated adverse events varies with the individual patient. Horses that have experienced adverse reactions from one NSAID may experience adverse reactions from another NSAID. Patients at greatest risk for adverse events are those that are dehydrated, on diuretic therapy, or those with existing renal, cardiovascular, and/or hepatic dysfunction. Concurrent administration of potentially nephrotoxic drugs should be carefully approached or avoided. NSAIDs may inhibit the prostaglandins that maintain normal homeostatic function. Such anti-prostaglandin effects may result in clinically significant disease in patients with underlying or pre-existing disease that has not been previously diagnosed. Since many NSAIDs possess the potential to produce gastrointestinal ulcerations and/or gastrointestinal perforation, concomitant use of EQUIOX X with other anti-inflammatory drugs, such as NSAIDs or corticosteroids, should be avoided. The concomitant use of protein bound drugs with EQUIOX X has not been studied in horses. The influence of concomitant drugs that may inhibit the metabolism of EQUIOX X has not been evaluated. Drug compatibility should be monitored in patients requiring adjunctive therapy. The safe use of EQUIOX X in horses less than one year in age, horses used for breeding, or in pregnant or lactating mares has not been evaluated. Consider appropriate washout times when switching from one NSAID to another NSAID or corticosteroid. Adverse Reactions: In controlled field studies, 127 horses (ages 3 to 37years) were evaluated for safety when given EQUIOX X Oral Paste at a dose of 0.045 mg/lb (0.1 mg/ kg) orally once daily for up to 14 days. The following adverse reactions were observed. Horses may have experienced more than one of the observed adverse reactions during the study. Adverse Reactions EQUIOX X n=127 Active Control n=125 Abdominal Pain 0 1 Diarrhea 2 0 E xcitation 1 0 Lethargy 0 1 Loose Stool 1 0 Polydipsia 0 1 Ur ticaria 0 1 In these field trials, EQUIOX X Oral Paste was safely used concomitantly with other therapies, including vaccines, anthelmintics, and antibiotics. The safety data sheet (SDS) contains more detailed occupational safety information. The safety and effectiveness of EQUIOX X Tablets was established in a relative bioavailability study comparing EQUIOX X Tablets and EQUIOX X (firocoxib) Oral Paste. Therefore, additional field studies were not performed to support the effectiveness of EQUIOX X Tablets. To report suspected adverse events, for technical assistance, or to obtain a copy of the SDS, contact Boehringer Ingelheim Animal Health USA Inc. at 1-888-637-4251. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at www.fda.gov/reportanimalae. Information for Owner or Person Treating Horse: A Client Information Sheet should be provided to the person treating the horse. Treatment administrators and caretakers should be aware of the potential for adverse reactions and the clinical signs associated with NSAID intolerance. Adverse reactions may include erosions and ulcers of the gums, tongue, lips and face, weightloss, colic, diarrhea, or icterus. Serious adverse reactions associated with this drug class can occur without warning and, in some situations, result in death. Clients should be advised to discontinue NSAID therapy and contact their veterinarian immediately if any of these signs of intolerance are observed. The majority of patients with drug-related adverse reactions recover when the signs are recognized, drug administration is stopped, and veterinary care is initiated. Clinical Pharmacology: Pharmacokinetics: When administered as a 0.045 mg/ lb (0.1 mg/kg) dose in oral paste to adult horses with normal access to roughage, feed, and water, the absolute bioavailability of firocoxib from EQUIOX X paste is approximately 79%. Following oral administration, drug peak concentration (Cmax) of 0.08 mcg/mL can be reached at 4 hours (Tmax) post-dosing. However, in some animals, up to 12 hours may be needed before significant plasma concentrations are observed. Little drug amount distributes into blood cells. The major metabolism mechanism of firocoxib in the horse is decyclopropylmethylation followed by glucuronidation of that metabolite. Based upon radiolabel studies, the majority of firocoxib is eliminated in the urine as the decyclopropylmethylated metabolite. Despite a high rate of plasma protein binding (98%), firocoxib exhibits a large volume of distribution (mean Vd(ss) = 1652 mL /kg). The terminal elimination half-life (T1 ⁄ 2) in plasma averages 30-40 hours after IV or oral paste dosing. Therefore, drug accumulation occurs with repeated dose administrations and steady state concentrations are achieved beyond 6-8 daily oral doses in the horse. Dose linearity exists from 1X-2 X of 0.1 mg/kg/day. Relative Bioavailability Study A pharmacokinetic study was conducted to compare the relative bioavailability of an oral firocoxib tablet containing 57 mg firocoxib (EQUIOX X Tablets; NADA 141-458) to the approved paste formulation (EQUIOX X Oral Paste; NADA 141-253). The criteria for the Test / Reference (T/R) ratios and the 90% Confidence Intervals (CI) of EQUIOX X Tablets (test product) were adjusted on the basis of the safety and effectiveness data for EQUIOX X Oral Paste (reference product). The lower bound of the 90% CI for effectiveness was defined by the minimal effective plasma concentration in the study used to support the dosage characterization of EQUIOX X Oral Paste. Effectiveness was based upon the area under the plasma drug concentration-time curve to the last quantifiable concentration (AUC last), with the effectiveness criteria set at a T/R ratio of greater than or equal to 0.77 and a corresponding lower bound for the 90% CI set at 0.71. The upper bound of the 90% CI for safety was defined by the maximum safe plasma concentration (Cmax) in the study used to establish a margin of safety for EQUIOX X Oral Paste. Based upon that margin of safety, product safety was defined as a T/R of less than or equal to 1.53, with a corresponding upper bound for the 90% CI of 1.71. Non-steroidal anti-inflammatory drug for oral use in horses only. CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Description: EQUIOX X ® (firocoxib) belongs to the coxib class of non- narcotic, non-steroidal anti-inflammatory drugs (NSAIDs). Firocoxib is a white crystalline compound described chemically as 3 (cyclopropylmethoxy)-4- (4- methylsulfonyl)phenyl)-5, 5-dimethylfuranone. The empirical formula is C17H20O5S, and the molecular weight is 336.4g/mol. The structural formula is shown below: Indications: EQUIOX X is administered once daily for up to 14 days for the control of pain and inflammation associated with osteoarthritis in horses. Dosage and Administration: Always provide the Client Information Sheet with the prescription.EQUIOX X is available as a paste or tablet. The recommended dosage of EQUIOX X (firocoxib) oral paste in horses is 0.045 mg/lb (0.1 mg/kg) of body weight once daily for up to 14 days. Each marking on the syringe will treat 250 pounds of body weight, and each notch corresponds to approximately a 50 lb weight increment. To deliver the correct dose, round the horse's body weight up to the nearest 50 pound increment (if the body weight is an exact 50 pound increment, do not round up). EQUIOX X may be given with or without food. 1) While holding plunger, turn the knurled ring on the plunger ¼ turn to the left and slide the knurled ring along the plunger shaft so that the side nearest the barrel is at the appropriate 50 lb weight notch, aligning the arrow on the plunger with the notch on the ring, as shown in the pictogram. 2) Lock the ring in place by making ¼ turn to the right. Ensure it is locked (it should no longer slide). The recommended dosage of EQUIOXX Tablets is one 57 mg tablet administered orally to horses weighing 800–1300 lbs, once daily for up to 14 days. For ease of administration, EQUIOXX Tablets may be given with food. The overall duration of treatment with any firocoxib formulation in horses, including EQUIOX X Tablets or Oral Paste, should not exceed 14 days. Contraindications: Horses with a hypersensitivity to firocoxib should not receive EQUIOX X ® . Warnings: For use in horses only. Do not use in horses intended for human consumption. Store EQUIOX X out of the reach of dogs and other pets in a secured location in order to prevent accidental ingestion or overdose.

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