Review of Nonsteroidal Anti-inflammatory Drugs in Horses

In an article published in the June 1 issue of the Journal of the American Veterinary Medical Association, authors from North Carolina State University College of Veterinary Medicine review the use of nonsteroidal anti-inflammatory drugs (NSAIDs), specifically firocoxib, in horses.

Key points from the study included the following:

• NSAIDs that selectively inhibit cyclooxygenase (COX)-2 and spare COX-1 may cause fewer adverse effects than nonselective NSAIDs.
• Firocoxib, a selective COX-2 inhibitor, is labeled for use in horses in the United States
• The Food and Drug Administration (FDA) limits the use of firocoxib in horses to formulations labeled for horses, not those labeled for dogs.
• Proper dosing of firocoxib maximizes its therapeutic effect and minimizes the risk for adverse effects.
• Combining NSAIDs increases the risk for adverse effects.

Cyclooxygenase Selectivity

NSAIDs reduce inflammation by inhibiting COX function. At least 3 COX isoforms exist; COX-1 and COX-2 are clinically relevant in horses.

COX-1 is expressed in nearly all tissues and is necessary for proper gastrointestinal (GI) function, renal function, and coagulation. COX-2 is also expressed at low levels in many tissues and contributes to normal kidney function. In addition, COX-2 is upregulated in inflammatory states, leading to increased production of prostaglandins that cause pain and inflammation.

Nonselective NSAIDs can be associated with adverse GI effects in horses because of COX-1 inhibition. Selective COX-2 inhibitors (which also inhibit COX-1 to a small degree) carry a lower risk for GI events. Because COX-2 is involved in kidney function, note the authors, administration of selective COX-2 inhibitors can still cause adverse renal effects in susceptible patients.

NSAIDs inhibit COX isoforms to various degrees:

• Nonselective NSAIDs such as phenylbutazone and flunixin meglumine inhibit COX-1 and COX-2 to a similar degree.
• Preferential COX-2 inhibitors inhibit COX-1 to a much lower degree than COX-2. Meloxicam and firocoxib fall into this category.
• Selective COX-2 inhibitors have an even higher degree of COX-2 selectivity. Examples include deracoxib, mavacoxib, robenacoxib, and cimicoxib.

Prescribing Firocoxib for Horses

Firocoxib is manufactured for horses as a chewable tablet, an oral paste, and an injection. Canine formulations of firocoxib are sometimes used off-label for horses because they are less expensive, say the authors. However, they write, practitioners should use equine formulations despite the cost difference. The FDA does not permit the extralabel use of canine-labeled firocoxib in horses because a formulation specifically labeled for horses is available.

The COX-2 selectivity of firocoxib decreases if the drug is overdosed, caution the authors. Doses higher than recommended can cause adverse effects similar to those of nonselective NSAIDs. Combining NSAIDs (for example, administering firocoxib and phenylbutazone together) has also been shown to increase the risk for adverse effects, including effects on the kidneys.

Effectiveness of COX-2 Inhibitors in Horses

Firocoxib is approved for the treatment of degenerative joint disease in horses. In one study, firocoxib and phenylbutazone had similar efficacy on lameness in horses. Results of other studies suggest that firocoxib is as effective as flunixin meglumine in controlling GI pain and that selective COX-2 inhibitors may reduce the risk for intestinal problems in horses with colic. Further investigation is needed to determine whether selective COX-2 inhibitors reduce the incidence of adverse GI effects in horses, say the authors.

Conclusion

Understanding the benefits of selective COX-2 inhibition, FDA restrictions on the use of canine firocoxib in horses, and the importance of proper firocoxib dosing “will help veterinarians select and treat patients that could benefit from this new class of NSAID,” conclude the authors.

Dr. Laurie Anne Walden received her doctorate in veterinary medicine from North Carolina State University. After an internship in small animal medicine and surgery at Auburn University, she returned to North Carolina, where she has been in small animal primary care practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing, LLC. She works as a full-time freelance medical writer and editor and continues to see patients a few days each month.