Update on the use of cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs in horses

Amanda Ziegler Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University. Raleigh, NC 27607.

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Callie Fogle Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University. Raleigh, NC 27607.

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Anthony Blikslager Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University. Raleigh, NC 27607.

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Abstract

Nonsteroidal anti-inflammatory drugs work through inhibition of cyclooxygenase (COX) and are highly effective for the treatment of pain and inflammation in horses. There are 2 clinically relevant isoforms of COX. Cyclooxygenase-1 is constitutively expressed and is considered important for a variety of physiologic functions, including gastrointestinal homeostasis. Thus, NSAIDs that selectively inhibit COX-2 while sparing COX-1 may be associated with a lower incidence of adverse gastrointestinal effects. Various formulations of firocoxib, a COX-2-selective NSAID, labeled for use in horses are available in the United States. Equine practitioners should know that the FDA limits the use of firocoxib to formulations labeled for horses, regardless of price concerns. In addition, practitioners will benefit from understanding the nuances of firocoxib administration, including the importance of correct dosing and the contraindications of combining NSAIDs. Together with knowledge of the potential advantages of COX-2 selectivity, these considerations will help veterinarians select and treat patients that could benefit from this new class of NSAID.

Abstract

Nonsteroidal anti-inflammatory drugs work through inhibition of cyclooxygenase (COX) and are highly effective for the treatment of pain and inflammation in horses. There are 2 clinically relevant isoforms of COX. Cyclooxygenase-1 is constitutively expressed and is considered important for a variety of physiologic functions, including gastrointestinal homeostasis. Thus, NSAIDs that selectively inhibit COX-2 while sparing COX-1 may be associated with a lower incidence of adverse gastrointestinal effects. Various formulations of firocoxib, a COX-2-selective NSAID, labeled for use in horses are available in the United States. Equine practitioners should know that the FDA limits the use of firocoxib to formulations labeled for horses, regardless of price concerns. In addition, practitioners will benefit from understanding the nuances of firocoxib administration, including the importance of correct dosing and the contraindications of combining NSAIDs. Together with knowledge of the potential advantages of COX-2 selectivity, these considerations will help veterinarians select and treat patients that could benefit from this new class of NSAID.

  • 1. Goodrich LR, Nixon AJ. Medical treatment of osteoarthritis in the horse—a review. Vet J 2006; 171: 5169.

  • 2. Clark JO, Clark TP. Analgesia. Vet Clin North Am Equine Pract 1999; 15: 705723.

  • 3. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971; 231: 232235.

  • 4. Vane JR, Botting RM. A better understanding of anti-inflammatory drugs based on isoforms of cyclooxygenase (COX-1 and COX-2). Adv Prostaglandin Thromboxane Leukot Res 1995; 23: 4148.

    • Search Google Scholar
    • Export Citation
  • 5. Simon LS, Weaver AL, Graham DY, et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. JAMA 1999; 282: 19211928.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343:15201528 (Expression of concern. N Engl J Med 2005; 353:2813–2814. Expression of concern reaffirmed. N Engl J Med 2006; 354:1193.).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Sibbald B. Rofecoxib (Vioxx) voluntarily withdrawn from market. CMAJ 2004; 171: 10271028.

  • 8. Atukorala I, Hunter DJ. Valdecoxib: the rise and fall of a COX-2 inhibitor. Expert Opin Pharmacother 2013; 14: 10771086.

  • 9. AVMA. Clarification regarding substitution of Previcox for Equioxx. Available at: www.avma.org/KB/Resources/Reference/Pages/Previcox-for-Equioxx.aspx. Accessed Jan 10, 2017.

    • Search Google Scholar
    • Export Citation
  • 10. Tomlinson JE, Wilder BO, Young KM, et al. Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia. Am J Vet Res 2004; 65: 761769.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Little D, Brown SA, Campbell NB, et al. Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum. Am J Vet Res 2007; 68: 614624.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Cook VL, Meyer CT, Campbell NB, et al. Effect of firocoxib or flunixin meglumine on recovery of ischemic-injured equine jejunum. Am J Vet Res 2009; 70: 9921000.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Campbell NB, Blikslager AT. The role of cyclooxygenase inhibitors in repair of ischaemic-injured jejunal mucosa in the horse. Equine Vet J Suppl 2000; 32: 5964.

    • Search Google Scholar
    • Export Citation
  • 14. Blikslager AT. Do we need cyclooxygenase-2 inhibitors in equine practice? Compend Contin Educ Pract Vet 1999; 21: 548550.

  • 15. Warner TD, Mitchell JA. Cyclooxygenase-3 (COX-3): filling in the gaps toward a COX continuum? Proc Natl Acad Sci USA 2002; 99: 1337113373.

  • 16. Cook VL, Blikslager AT. The use of nonsteroidal anti-inflammatory drugs in critically ill horses. J Vet Emerg Crit Care (San Antonio) 2015; 25: 7688.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Kivett L, Taintor J, Wright J. Evaluation of the safety of a combination of oral administration of phenylbutazone and firocoxib in horses. J Vet Pharmacol Ther 2014; 37: 413416.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Duz M, Parkin TD, Cullander RM, et al. Effect of flunixin meglumine and firocoxib on ex vivo cyclooxygenase activity in horses undergoing elective surgery. Am J Vet Res 2015; 76: 208215.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Brideau C, Van Staden C, Chan CC. In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs, and cats. Am J Vet Res 2001; 62: 17551760.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Beretta C, Garavaglia G, Cavalli M. COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. Pharmacol Res 2005; 52: 302306.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Kim TW, Della Rocca G, Di Salvo A, et al. Evaluation of pharmacokinetic and pharmacodynamic properties of cimicoxib in fasted and fed horses. N Z Vet J 2015; 63: 9297.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Kim TW, Lebkowska-Wieruszewska B, Owen H, et al. Pharmacokinetic profiles of the novel COX-2 selective inhibitor cimicoxib in dogs. Vet J 2014; 200: 7781.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Bienhoff SE, Smith ES, Roycroft LM, et al. Efficacy and safety of deracoxib for control of postoperative pain and inflammation associated with soft tissue surgery in dogs. Vet Surg 2012; 41: 336344.

    • Search Google Scholar
    • Export Citation
  • 24. Reymond N, Speranza C, Gruet P, et al. Robenacoxib vs carprofen for the treatment of canine osteoarthritis; a randomized, noninferiority clinical trial. J Vet Pharmacol Ther 2012; 35: 175183.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Payne-Johnson M, Becskei C, Chaudhry Y, et al. Comparative efficacy and safety of mavacoxib and carprofen in the treatment of canine osteoarthritis. Vet Rec 2015; 176: 284.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Freedom of information summary. Original new animal drug application. NADA 141–458. Equioxx, firocoxib tablets, horses. Available at: www.fda.gov/downloads/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/FOIADrugSummaries/UCM514663.pdf. Accessed Jan 18, 2017.

    • Search Google Scholar
    • Export Citation
  • 27. Lascelles BD, Blikslager AT, Fox SM, et al. Gastrointestinal tract perforation in dogs treated with a selective cyclooxygenase-2 inhibitor: 29 cases (2002–2003). J Am Vet Med Assoc 2005; 227: 11121117.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. United States Equestrian Federation. 2016 guidelines for drugs and medications. Columbus, Ohio: United States Equestrian Federation, 2016.

    • Search Google Scholar
    • Export Citation
  • 29. Orsini JA, Ryan WG, Carithers DS, et al. Evaluation of oral administration of firocoxib for the management of musculoskeletal pain and lameness associated with osteoarthritis in horses. Am J Vet Res 2012; 73: 664671.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Doucet MY, Bertone AL, Hendrickson D, et al. Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. J Am Vet Med Assoc 2008; 232: 9197.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Davis JL, Papich MG, Morton AJ, et al. Pharmacokinetics of etodolac in the horse following oral and intravenous administration. J Vet Pharmacol Ther 2007; 30: 4348.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Naylor RJ, Taylor AH, Knowles E, et al. Comparison of flunixin meglumine and meloxicam for postoperative management of horses with strangulating small intestinal lesions. Equine Vet J 2014; 46: 427434.

    • Crossref
    • Search Google Scholar
    • Export Citation

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