Firocoxib

Firocoxib Chewable Tablets are indicated for the control of pain and inflammation associated with osteoarthritis and for the control of postoperative pain and inflammation associated with soft-tissue and orthopedic surgery in dogs.

Firocoxib Chewable Tablets

For the control of pain and inflammation associated with osteoarthritis and for the control of postoperative pain and inflammation associated with soft-tissue and orthopedic surgery in dogs.

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Previcox®

For the control of pain and inflammation associated with osteoarthritis in horses.

Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian. For intravenous use in horses only.

Equioxx® Injection

Indications: PREVICOX (firocoxib) Chewable Tablets are indicated for the control of pain and inflammation associated with osteoarthritis and for the control of postoperative pain and inflammation associated with soft-tissue and orthopedic surgery in dogs.

PREVICOX® (firocoxib) Chewable Tablets

OstiCoxib (firocoxib) Chewable Tablets are indicated for the control of pain and inflammation associated with osteoarthritis and for the control of postoperative pain and inflammation associated with soft-tissue and orthopedic surgery in dogs.

FDA application 200-722

Firocoxib Chewable Tablets for Dogs are indicated for the control of pain and inflammation associated with osteoarthritis and for the control of post-operative pain and inflammation associated with soft-tissue and orthopedic surgery in dogs.

Firocoxib Chewable Tablets for Dogs

Firocoxib Tablets for Horses are administered once daily for up to 14 days for the control of pain and inflmmation associated with osteoarthrtis in horses.

Firocoxib Tablets for Horses

EquiCoxib Oral Solution is administered for up to 14 days for the control of pain and inflammation associated with osteoarthritis in horses.

EquiCoxib™(firocoxib)Oral Solution for Horses

Relative Bioavailability Study A pharmacokinetic study was conducted to compare the relative bioavailability of an oral firocoxib tablet containing 57 mg firocoxib to the approved paste formulation. The criteria for the Test/Reference (T/R) ratios and the 90% Confidence Intervals (CI) of firocoxib tablets (test product) were adjusted on the basis of the safety and effectiveness data for firocoxib 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 firocoxib oral paste. Effectiveness was based upon the area under the plasma drug concentration-time curve to the last quantifiable concentration (AUClast), with the effectiveness criteria set at a T/R ratio of greater than or equal to 0.77 and a last 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 the firocoxib 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. The relative bioavailability study was a randomized, two period, two sequence crossover study in thirty horses. Each horse received a single tablet (57 mg firocoxib) and a single tube of paste (56.7 mg firocoxib). Blood samples were collected at 15 minutes, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48,72, 96 and 120 hours following each treatment. Samples were analyzed by LC-MS/MS for firocoxib concentrations. The results of the relative bioavailability study are summarized in Table 2. The Cmax and AUClast of firocoxib tablets were within the adjusted 90% CI for safety and effectiveness and met the criteria established for successfully demonstrating that firocoxib tablets will be safe and effective. Therefore, firocoxib tablets and firocoxib oral paste are acceptable as pharmaceutical alternatives. There was a substantial difference in the Tmax (time to maximum plasma concentration) between firocoxib oral paste and firocoxib tablets. The Tmax ranged from 0.25-4 hours for firocoxib oral paste and 0.25-12 hours for firocoxib tablets. The difference in the rate and extent of absorption was greatest within the first three hours after administration. The mean terminal elimination half-life of firocoxib oral paste (45.45 hours) was similar to that of firocoxib tablets (44.49 hours). Table 2: Relative Bioavailability Results for firocoxib oral paste (Reference) and firocoxib tablets (Test) (n=30 horses) Parameter Units Reference Geometric Mean Test Geometric Mean Test/ Reference Lower 90% CI Upper 90% CI Cmax ng/mL 78.44 58.85 0.75 67.92 82.88 AUClast hr*ng/mL 2515.77 2336.32 0.93 86.37 99.85 Cmax = maximum observed plasma concentration AUClast = Area Under the Curve to the last quantifiable time point CI= Confidence Interval The major metabolism mechanism of firocoxib in the horse is decyclopropylmethylation followed by glucuronidation of that metabolite. Based upon radiolabel studies done for the firocoxib paste formulation, the majority of firocoxib is eliminated in the urine as the decyclopropylmethylated metabolite. Despite a high degree 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, oral paste or tablet dosing. Therefore, drug accumulation occurs with repeated dose administrations and steady state concentrations are achieved beyond 6-8 daily oral doses in the horse. Mode of Action Firocoxib Tablets for Horses is a cyclooxygenase-inhibiting (coxib) class, non-narcotic, non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic activity1 in animal models. Based on in vitro horse data, firocoxib is a selective inhibitor of prostaglandin biosynthesis through inhibition of the inducible cyclooxygenase-2-isoenzyme (COX-2)2 . Firocoxib selectivity for the constitutive isoenzyme, cyclooxygenase-1 (COX-1) is relatively low. However, the clinical significance of these in vitro selectivity findings has not been established.

Firocoxib Tablets for Horses 57 mg

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 oral 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-2X of 0.1 mg/kg/day. Mode of action: EquiCoxib (firocoxib) is a cyclooxygenase-inhibiting (coxib) class, non-narcotic, non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic activity1 in animal models. Based on in vitro horse data, firocoxib is a selective inhibitor of prostaglandin biosynthesis through inhibition of inducible cyclooxygenase-2-isoenzyme (COX-2)2. Firocoxib selectivity for the constitutive isoenzyme, cyclooxygenase-1 (COX-1) is relatively low. However, the clinical significance of these in vitro selectivity findings has not been established.

EquiCoxib™(firocoxib)Oral Solution for Horses

Clinical Pharmacology: Mode of action: Firovet (firocoxib) is a cyclooxygenase-inhibiting (coxib) class, non-narcotic, non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. There are two main cyclooxygenase enzymes, COX-1 and COX-2, and a newly discovered third enzyme, COX-3, which has yet to be fully characterized.1 Cyclooxygenase-1 (COX-1) is the enzyme responsible for facilitating constitutive physiologic processes, e.g., platelet aggregation, gastric mucosal protection, and renal perfusion.2 It also is constitutively expressed in the brain, spinal cord, and reproductive tract.3 Cyclooxygenase-2 (COX-2) is responsible for the synthesis of inflammatory mediators, but it is also constitutively expressed in the brain, spinal cord and kidneys.4,5,6 Cyclooxygenase-3 (COX-3) is also constitutively expressed in the canine and human brain and also the human heart.7 Results from in vitro studies showed firocoxib to be highly selective for the COX-2 enzyme when canine blood was exposed to drug concentrations comparable to those observed following a once daily 5 mg/kg oral dose in dogs.8 However, the clinical significance of these findings has not been established.

Firovet™(firocoxib) Chewable Tablets

Mode of action: Firocoxib Chewable Tablets for Dogs is a cyclooxygenaseinhibiting (coxib) class, non-narcotic, non-ste- roidal anti-inflammatory drug (NSAID) with anti- inflammatory and analgesic properties. There are two main cyclooxygenase enzymes, COX-1 and COX-2, and a newly discovered third enzyme, COX-3, which has yet to be fully characterized.1 Cyclooxygenase-1 (COX-1) is the enzyme responsible for facilitating constitutive physiologic processes, e.g., platelet aggregation, gastric mucosal protection, and renal perfusion.2 It also is constitutively expressed in the brain, spinal cord, and reproductive tract.3 Cyclooxygenase-2 (COX-2) is responsible for the synthesis of inflammatory mediators, but it is also constitutively expressed in the brain, spinal cord and kidneys.4, 5, 6 Cyclooxygenase-3 (COX-3) is also constitutively expressed in the canine and human brain and also the human heart.7 Results from in vitro studies showed firocoxib to be highly selective for the COX-2 enzyme when canine blood was exposed to drug concentrations comparable to those observed following a once daily 5 mg/kg oral dose in dogs.8 However, the clinical significance of these findings has not been established.

Firocoxib Chewable Tablets for Dogs

Dogs with known hypersensitivity to firocoxib should not receive Firocoxib Chewable Tablets for Dogs.

Firocoxib Chewable Tablets for Dogs

Contraindications: Dogs with known hypersensitivity to firocoxib should not receive PREVICOX.

PREVICOX® (firocoxib) Chewable Tablets

Horses with a hypersensitivity to firocoxib should not receive Firocoxib Tablets for Horses.

Firocoxib Tablets for Horses

Horses with hypersensitivity to firocoxib should not receive EquiCoxib Oral Solution.

EquiCoxib™(firocoxib)Oral Solution for Horses

Horses with a hypersensitivity to firocoxib should not receive EQUIOXX® Tablets.

Equioxx® (firocoxib) Tablets 57 mg

Horses with a hypersensitivity to firocoxib should not receive OstiCoxib EQ.

OstiCoxib™ EQ (Firocoxib Tablets for Horses) 57 mg

Dogs with known hypersensitivity to firocoxib should not receive OstiCoxib.

FDA application 200-722

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. For oral use in dogs only. Use of this product at doses above the recommended 2.27 mg/lb (5.0 mg/kg) in puppies less than seven months of age has been associated with serious adverse reactions, including death (see Animal Safety). Due to tablet sizes and scoring, dogs weighing less than 12.5 lb (5.7 kg) cannot be accurately dosed. All dogs should undergo a thorough history and physical examination before the initiation of NSAID therapy. Appropriate laboratory testing to establish hematological and serum baseline data is recommended prior to and periodically during administration of any NSAID. Owners should be advised to observe for signs of potential drug toxicity (see Adverse Reactions and Animal Safety) and be given a Client Information Sheet about Firocoxib chewable tablets. To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet, contact Covetrus® North America at (855) 724-3461 or covetrus.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae Keep Firocoxib in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

Firocoxib Chewable Tablets For oral use in dogs only.

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. For oral use in dogs only. Use of this product at doses above the recommended 2.27 mg/lb (5.0 mg/kg) in puppies less than seven months of age has been associated with serious adverse reactions, including death (see Animal Safety). Due to tablet sizes and scoring, dogs weighing less than 12.5 lb (5.7 kg) cannot be accurately dosed. All dogs should undergo a thorough history and physical examination before the initiation of NSAID therapy. Appropriate laboratory testing to establish hematological and serum baseline data is recommended prior to and periodically during administration of any NSAID. Owners should be advised to observe for signs of potential drug toxicity (see Adverse Reactions and Animal Safety) and be given a Client Information Sheet about OstiCoxib. To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet, contact Felix Pharmaceuticals Private Limited at 1-833-571-1525. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae Keep OstiCoxib in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

OstiCoxib® (firocoxib chewable tablets) For oral use in dogs only.

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. For oral use in dogs only. Use of this product at doses above the recommended 2.27 mg/lb (5.0 mg/kg) in puppies less than seven months of age has been associated with serious adverse reactions, including death (see Animal Safety). Due to tablet sizes and scoring, dogs weighing less than 12.5 lb (5.7 kg) cannot be accurately dosed. All dogs should undergo a thorough history and physical examination before the initiation of NSAID therapy. Appropriate laboratory testing to establish hematological and serum baseline data is recommended prior to and periodically during adminstration of any NSAID. Owners should be advised to observe for signs of potential drug toxicity (see Adverse Reactions and Animal Safety) and be given a Client Information Sheet about Firovet chewable tablets. To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet, contact Dechra at 1-866-933-2472. For additional information about adverse drug experience reporting for animal drugs, contact FDAat 1-888-FDA-VETS or http://www.fda.gov/reportanimalae Keep Firovet in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

Firovet™(firocoxib) Chewable Tablets

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. For oral use in dogs only. Use of this product at doses above the recommended 2.27 mg/lb (5.0 mg/kg) in puppies less than seven months of age has been associated with serious adverse reactions, including death (see Animal Safety). Due to tablet sizes and scoring, dogs weighing less than 12.5 lb (5.7 kg) cannot be accurately dosed. All dogs should undergo a thorough history and physical examination before the initiation of NSAID therapy. Appropriate laboratory testing to establish hematological and serum baseline data is recommended prior to and periodically during administration of any NSAID. Owners should be advised to observe for signs of potential drug toxicity (see Adverse Reactions and Animal Safety) and be given a Client Information Sheet about PREVICOX Chewable Tablets. For technical assistance or to report suspected adverse events, call 1-888-637-4251. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae.

PREVICOX® (firocoxib) Chewable Tablets

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. Keep Firocoxib Chewable Tablets for Dogs in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose. For oral use in dogs only. Use of this product at doses above the recommended 2.27 mg/lb (5.0 mg/ kg) in puppies less than seven months of age has been associated with serious adverse reactions, including death (see Animal Safety). Due to tablet sizes and scoring, dogs weighing less than 12.5 lb (5.7 kg) cannot be accurately dosed. All dogs should undergo a thorough history and physical examination before the initiation of NSAID therapy. Appropriate laboratory testing to establish hematological and serum baseline data is recommended prior to and periodically during administration of any NSAID. Owners should be advised to observe for signs of potential drug toxicity (see Adverse Reactions and Animal Safety) and be given a Client Information Sheet about Firocoxib Chewable Tablets for Dogs.

Firocoxib Chewable Tablets for Dogs

For oral use in horses only. Do not use in horses intended for human consumption. Human Warnings: Not for use in humans. Keep this and all medications out of the reach of children. Wash hands with soap and water after use. Consult a physician in case of accidental ingestion by humans. Animal Safety: Clients should be advised to observe for signs of potential drug toxicity and be given a Client Information Sheet with each prescription. Keep EquiCoxib in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose. To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), contact Aurora Pharmaceutical at 1-888-215-1256 or www.aurorapharmaceutical.com. 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.

EquiCoxib™(firocoxib)Oral Solution for Horses

For use in horses only. Do not use in horses intended for human consumption. Store Firocoxib Tablets for Horses out of the reach of dogs and other pets in a secured location in order to prevent accidental ingestion or overdose. 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.

Firocoxib Tablets for Horses

For use in horses only. Do not use in horses intended for human consumption. Keep Firocoxib Tablets for Horses in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

Firocoxib Tablets for Horses 57 mg

For use in horses only. Do not use in horses intended for human consumption. Store EQUIOXX Tablets out of the reach of dogs and other pets in a secured location in order to prevent accidental ingestion or overdose.

Equioxx® (firocoxib) Tablets 57 mg

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.

Equioxx® (firocoxib) Tablets 57 mg

Osteoarthritis: In controlled field studies, 128 dogs (ages 11 months to 15 years) were evaluated for safety when given firocoxib chewable tablets at a dose of 2.27 mg/lb (5.0 mg/kg) orally once daily for 30 days. The following adverse reactions were observed. Dogs may have experienced more than one of the observed adverse reactions during the study. Adverse Reactions Seen in U.S. Field Studies Adverse Reactions Firocoxib n=128 Active Control n=121 Vomiting 5 8 Diarrhea 1 10 Decreased Appetite or Anorexia 3 3 Lethargy 1 3 Pain 2 1 Somnolence 1 1 Hyperactivity 1 0 Firocoxib chewable tablets were safely used during field studies concomitantly with other therapies, including vaccines, anthelmintics, and antibiotics. Soft-tissue Surgery: In controlled field studies evaluating soft-tissue postoperative pain and inflammation, 258 dogs (ages 10.5 weeks to 16 years) were evaluated for safety when given firocoxib chewable tablets at a dose of 2.27 mg/lb (5.0 mg/kg) orally approximately 2 hours prior to surgery and once daily thereafter for up to two days. The following adverse reactions were observed. Dogs may have experienced more than one of the observed reactions during the study. Adverse Reactions Seen in the Soft-tissue Surgery Postoperative Pain Field Studies Adverse Reactions Firocoxib Group n=127 Control Group* n=131 Vomiting 5 6 Diarrhea 1 1 Brusing at Surgery Site 1 1 Respiratory Arrest 1 0 SQ Crepitus in Rear Leg and Flank 1 0 Swollen Paw 1 0 *Sham-dosed (pilled) Orthopedic Surgery: In a controlled field study evaluating orthopedic postoperative pain and inflammation, 226 dogs of various breeds, ranging in age from 1 to 11.9 years in the firocoxib-treated groups and 0.7 to 17 years in the control group were evaluated for safety. Of the 226 dogs, 118 were given firocoxib chewable tablets at a dose of 2.27 mg/lb (5.0 mg/kg) orally approximately 2 hours prior to surgery and once daily thereafter for a total of three days. The following adverse reactions were observed. Dogs may have experienced more than one of the observed reactions during the study. Adverse Reactions Seen in the Orthopedic Surgery Postoperative Pain Field Study Adverse Reactions Firocoxib Group n=118 Control Group* n=108 Vomiting 1 0 Diarrhea 2** 1 Bruising at Surgery Site 2 3 Inappetence/Decreased Appetite 1 2 Pyrexia 0 1 Incision Swelling, Redness 9 5 Oozing Incision 2 0 A case may be represented in more than one category. *Sham-dosed (pilled). **One dog had hemorrhagic gastroenteritis. Post-Approval Experience (Rev. 2009): The following adverse reactions are based on post-approval adverse drug event reporting. The categories are listed in decreasing order of frequency by body system: Gastrointestinal: vomiting, anorexia, diarrhea, melena, gastrointestinal perforation, hematemesis, hematochezia, weight loss, gastrointestinal ulceration, peritonitis, abdominal pain, hypersalivation, nausea Urinary: elevated BUN, elevated creatinine, polydypsia, polyuria, hematuria, urinary incontinence, proteinuria, kidney failure, azotemia, urinary tract infection Neurological/Behavioral/Special Sense: depression/lethargy, ataxia, seizures, nervousness, confusion, weakness, hyperactivity, tremor, paresis, head tilt, nystagmus, mydriasis, aggression, uveitis. Hepatic: elevated ALP, elevated ALT, elevated bilirubin, decreased albumin, elevated AST, icterus, decreased or increased total protein and globulin, pancreatitis, ascites, liver failure, decreased BUN Hematological: anemia, neutrophilia, thrombocytopenia, neutropenia Cardiovascular/Respiratory: tachypnea, dyspnea, tachycardia Dermatologic/Immunologic: pruritis, fever, alopecia, moist dermatitis, autoimmune hemolytic anemia, facial/muzzle edema, urticaria In some cases, death has been reported as an outcome of the adverse events listed above.

OstiCoxib® (firocoxib chewable tablets) For oral use in dogs only.

The safety and effectiveness of EQUIOXX Tablets was established in a relative bioavailability study comparing EQUIOXX Tablets and EQUIOXX (firocoxib) Oral Paste. Therefore, additional field studies were not performed to support the effectiveness of EQUIOXX Tablets. In controlled field studies, 127 horses (ages 3 to 37 years) were evaluated for safety when given EQUIOXX 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. Table 1: Adverse Reactions Seen in U.S. Field Studies with EQUIOXX Oral Paste: Adverse Reactions EQUIOXX n = 127 Active Control n = 125 Abdominal pain 0 1 Diarrhea 2 0 Excitation 1 0 Lethargy 0 1 Loose stool 1 0 Polydipsia 0 1 Urticaria 0 1 In these field trials, EQUIOXX 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. 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 http://www.fda.gov/AnimalVeterinary/SafetyHealth.

Equioxx® (firocoxib) Tablets 57 mg

The safety and effectiveness of firocoxib tablets was established in a relative bioavailability study comparing firocoxib tablets and firocoxib oral paste. Therefore, additional field studies were not performed to support the effectiveness of firocoxib tablets. In controlled field studies, 127 horses (ages 3 to 37 years) were evaluated for safety when given firocoxib 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. Table 1: Adverse Reactions Seen in U.S. Field Studies with firocoxib oral paste: Adverse Reactions Firocoxib n = 127 Active control n = 125 Abdominal Pain 0 1 Diarrhea 2 0 Excitation 1 0 Lethargy 0 1 Loose stool 1 0 Polydipsia 0 1 Uticaria 0 1 In these field trials, firocoxib 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. To report suspected adverse events, for technical assistance, or to obtain a copy of the SDS, contact Pegasus Laboratories at 1-800-874-9764. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/reportanimalae.

Firocoxib Tablets for Horses

In controlled field studies, 127 horses (ages 3 to 37 years) were evaluated for safety when given firocoxib 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 Seen in U.S. Field Studies Firocoxib was safely used concomitantly with other therapies, including vaccines, anthelmintics, and antibiotics, during the field studies. The safety data sheet (SDS) contains more detailed occupational safety information. To report suspected adverse drug events, for technical assistance, or to obtain a copy of the Safety Data Sheet (SDS), contact Aurora Pharmaceutical Inc. at 1-888-215-1256 or www.aurorapharmaceutical.com. 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. Adverse Reactions Firocoxib n=127 Active Control n=125 Abdominal pain 0 1 Diarrhea 2 0 Excitation 1 0 Lethargy 0 1 Loose stool 1 0 Polydipsia 0 1 Urticaria 0 1

EquiCoxib™(firocoxib)Oral Solution for Horses

The safety and effectiveness of firocoxib tablets was established in a relative bioavailability study comparing firocoxib tablets and firocoxib oral paste. Therefore, additional field studies were not performed to support the effectiveness of firocoxib tablets. In controlled field studies, 127 horses (ages 3 to 37 years) were evaluated for safety when given firocoxib 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. Table 1: Adverse Reactions Seen in U.S. Field Studies with firocoxib oral paste: Adverse Reactions Firocoxib n=127 Active Control n=125 Abdominal pain 0 1 Diarrhea 2 0 Excitation 1 0 Lethargy 0 1 Loose stool 1 0 Polydipsia 0 1 Urticaria 0 1 In these field trials, firocoxib 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.

Firocoxib Tablets for Horses 57 mg

Adverse Reactions:

PREVICOX® (firocoxib) Chewable Tablets

One intravenous injection once daily for up to 5 days, at a dose of 0.04 mg/lb (0.09 mg/kg) body weight (BW). If further treatment is needed EQUIOXX (firocoxib) Oral Paste for horses can be used at a dosage of 0.045 mg/lb (0.1 mg/kg) body weight for up to an additional 9 days of treatment. The overall duration of treatment EQUIOXX Injection and EQUIOXX Oral Paste will be dependent on the response observed, but should not exceed 14 days.

Intravenous

Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian. For intravenous use in horses only.

Equioxx® Injection

One 57 mg tablet administered orally to horses weighing 800 – 1300 lbs, once daily for up to 14 days.

Oral

Firocoxib Tablets for Horses

Administer one 57 mg tablet daily for horses weighing 800-1300 lbs for up to 14 days duration.

Oral

For use in horses only. Do not use in horses intended for human consumption.

Equioxx®

Administer one 57-mg tablet to horses weighing 800 to 1,300 lb once daily for up to 14 days.

Oral

Firocoxib Tablets for Horses

0.1 mg per kilogram (0.045 mg per pound) body weight daily for up to 14 days.

Oral

Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Equioxx® Oral Paste

0.045 mg/lb (0.1 mg/kg) of body weight once daily for up to 14 days

Oral

EquiCoxib®

5 mg/kg (2.27 mg/lb) body weight. Administer once daily as needed for osteoarthritis and for 3 days as needed for postoperative pain and inflammation associated with soft-tissue and orthopedic surgery. Administer approximately 2 hours before soft-tissue or orthopedic surgery.

Oral

Firocoxib Chewable Tablets for Dogs

2.27 mg/lb (5.0 mg/kg) body weight once daily as needed for osteoarthritis and for 3 days as needed for postoperative pain and inflammation associated with soft-tissue and orthopedic surgery. Administer approximately 2 hours prior to surgery.

Oral

Firox™

EquiCoxib Oral Dosing Guide Body Weight (lb) Dose Volume (mL) 250 1.25 mL 500 2.5 mL 750 3.75 mL 1000 5 mL 1250 6.25 mL 1) Remove draw-off cap. Peel off the foil-backed seal from the bottle. 2) Screw the draw-off cap tightly back on the bottle. 3) Remove the seal from the top of the cap exposing the cross-hatched opening in the center of the silicone liner. 4) Remove the provided oral dosing syringe from its plastic cover. 5) Insert the oral dosing syringe firmly into the cross-hatched opening of the caps silicone liner. 6) Turn the bottle with attached syringe upside down. Pull back the syringe plunger until the widest portion of the plunger lines up with the line that corresponds with the animals weight. Each line between the 250 lb increments corresponds to 50 lb. 7) Turn the bottle with attached syringe right side up and separate the dosing syringe from the bottle. 8) Give orally according to your veterinarians instructions. DO NOT INJECT.

ORAL

EquiCoxib™(firocoxib)Oral Solution for Horses

Always provide the Client Information Sheet with prescription. Carefully consider the potential benefits and risks of Firocoxib Chewable Tablets for Dogs and other treatment options before deciding to use Firocoxib Chewable Tablets for Dogs. Use the lowest effective dose for the shortest duration consistent with individual response. The recommended dosage of Firocoxib Chewable Tablets for Dogs for oral administration in dogs is 2.27 mg/lb (5.0 mg/kg) body weight once daily as needed for osteoarthritis and for 3 days as needed for postoperative pain and inflammation associated with soft-tissue and orthopedic surgery. The dogs can be treated with Firocoxib Chewable Tablets for Dogs approximately two hours prior to surgery. The tablets are scored and dosage should be calculated in half tablet increments. Firocoxib Chewable Tablets for Dogs can be administered with or without food.

ORAL

Firocoxib Chewable Tablets for Dogs

Dosage and Administration: Always provide the Client Information Sheet with prescription. Carefully consider the potential benefits and risks of PREVICOX and other treatment options before deciding to use PREVICOX. Use the lowest effective dose for the shortest duration consistent with individual response. The recommended dosage of PREVICOX (firocoxib) for oral administration in dogs is 2.27 mg/lb (5.0 mg/kg) body weight once daily as needed for osteoarthritis and for 3 days as needed for postoperative pain and inflammation associated with soft-tissue and orthopedic surgery. The dogs can be treated with PREVICOX approximately two hours prior to surgery. The tablets are scored and dosage should be calculated in quarter tablet increments. Use split tablets within 30 days. PREVICOX Chewable Tablets can be administered with or without food.

ORAL

PREVICOX® (firocoxib) Chewable Tablets

Always provide the Client Information Sheet with the prescription. The recommended dosage of EquiCoxib (firocoxib) for oral administration in horses is 0.045 mg/lb (0.1 mg/kg) of body weight once daily for up to 14 days. In target animal safety studies, toxicity was seen at the recommended dose when the duration of treatment exceeded 30 days. Only administer EquiCoxib with the provided dosing syringe. Each 1.25 mL volume will treat 250 pounds of body weight and each additional 0.25 mL volume corresponds to approximately a 50 lb weight increment. The provided dosing syringe is calibrated so that each line corresponds to a 50 lb weight increment. To deliver the correct dose, round the horse's body weight up to the nearest 50 pound increment (if body weight is an exact 50 pound increment, do not round up).

ORAL

EquiCoxib™(firocoxib)Oral Solution for Horses

Dosage and Administration: Always provide the Client Information Sheet with prescription. Carefully consider the potential benefits and risks of Firovet and other treatment options before deciding to use Firovet. Use the lowest effective dose for the shortest duration consistent with individual response. The recommended dosage of Firovet (firocoxib) for oral administration in dogs is 2.27 mg/lb (5.0 mg/kg) body weight once daily as needed for osteoarthritis and for 3 days as needed for postoperative pain and inflammation associated with soft-tissue and orthopedic surgery. The dogs can be treated with Firovet approximately two hours prior to surgery. The tablets are scored and dosage should be calculated in half tablet increments. Firovet chewable tablets can be administered with or without food.

ORAL

Firovet™(firocoxib) Chewable Tablets

Always provide the Client Information Sheet with prescription. Carefully consider the potential benefits and risks of OstiCoxib and other treatment options before deciding to use OstiCoxib. Use the lowest effective dose for the shortest duration consistent with individual response. The recommended dosage of OstiCoxib (firocoxib) for oral administration in dogs is 2.27 mg/lb (5.0 mg/kg) body weight once daily as needed for osteoarthritis and for 3 days as needed for postoperative pain and inflammation associated with soft-tissue and orthopedic surgery. The dogs can be treated with OstiCoxib approximately two hours prior to surgery. The tablets are scored and dosage should be calculated in half tablet increments. OstiCoxib Chewable Tablets can be administered with or without food.

ORAL

FDA application 200-722

Always provide the Client Information Sheet with prescription. Carefully consider the potential benefits and risks of Flexira and other treatment options before deciding to use Flexira. Use the lowest effective dose for the shortest duration consistent with individual response. The recommended dosage of Flexira (firocoxib) for oral administration in dogs is 2.27 mg/lb (5.0 mg/kg) body weight once daily as needed for osteoarthritis and for 3 days as needed for postoperative pain and inflammation associated with soft-tissue and orthopedic surgery. The dogs can be treated with Flexira approximately two hours prior to surgery. The tablets are scored and dosage should be calculated in half tablet increments. Flexira Chewable Tablets can be administered with or without food.

ORAL

FLEXIRA™ (firocoxib)

Always provide the Client Information Sheet with the prescription. The recommended dosage of Firocoxib Tablets for Horses is one 57 mg tablet administered orally to horses weighing 800 – 1300 lbs, once daily for up to 14 days. For ease of administration, Firocoxib Tablets for Horses may be given with food. The overall duration of treatment with any firocoxib formulation in horses, including Firocoxib Tablets for Horses, firocoxib injection or firocoxib oral paste, should not exceed 14 days. Please see the package insert for firocoxib injection or firocoxib oral paste for appropriate prescribing information for those formulations.

ORAL

Firocoxib Tablets for Horses 57 mg

Always provide the Client Information Sheet with the prescription. 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 EQUIOXX Tablets, Injection or Oral Paste, should not exceed 14 days. Please see the package insert for EQUIOXX Injection or Oral Paste for appropriate prescribing information for those formulations.

ORAL

Equioxx® (firocoxib) Tablets 57 mg