Systemic Effects of Topical Ophthalmic NSAIDs in Dogs

In the Literature

Van Vertloo LR, Sebbag L, Allbaugh RA, Allenspach K, Borts DJ, Mochel JP. Systemic absorption and gastrointestinal adverse effects from topical ketorolac and diclofenac ophthalmic solutions in healthy dogs. J Am Vet Med Assoc. 2024;262(7):940-949. doi:10.2460/javma.23.12.0707

The Research …

Topical ophthalmic medications are an integral component of ocular disease management and can achieve high local drug levels. Systemic absorption and subsequent risk for adverse effects may be assumed to be low; however, topical medications are absorbed systemically at variable levels influenced by local physiology (eg, nasolacrimal drainage, conjunctival vascular absorption), local disease states (eg, inflammation), and unique drug properties (eg, molecular weight, pH).¹

This study evaluated systemic absorption and GI adverse effects of ketorolac and diclofenac (common, commercially available ophthalmic NSAIDs) in clinically healthy, 2-year-old beagles with normal ophthalmic examination results. Dogs were given 1 drop of either ketorolac (n = 6) or diclofenac (n = 5) in each eye 4 times daily for 28 days. Clinical signs (ie, vomiting, feces, appetite), fecal occult blood testing, CBC, serum chemistry profile, reticulocyte count, and gastroduodenoscopy (with previously established scoring for lesion severity) were evaluated at various time points to assess GI adverse effects. Plasma concentrations of the medications were also measured at multiple time points. 

Vomiting, hematochezia, and decreased appetite were noted infrequently in the ketorolac treatment group. All fecal occult blood tests were negative. Clinicopathologic changes were minimal in both groups, except increased BUN:creatinine ratio in the ketorolac group at the end of the study. Gastroduodenoscopy revealed the most significant results: ulcers and/or erosions developed in 1 of 5 dogs in the diclofenac group and all 6 dogs in the ketorolac group. When all sites were combined, dogs in the ketorolac group had higher endoscopy scores compared with the diclofenac group. In addition, the antrum was significantly more affected in the ketorolac group. Plasma drug levels were significantly correlated with total and antral endoscopy scores in the ketorolac group but not the diclofenac group.

… The Takeaways

Key pearls to put into practice:

• Topical ophthalmic NSAIDs are important for management of ocular surface and intraocular inflammatory conditions, but potential for systemic adverse effects should be considered.

• A retrospective study that supports the potential for systemic adverse effects identified similar incidence of GI bleeding in dogs receiving topical ophthalmic NSAIDs alone, oral NSAIDs alone, or oral corticosteroids alone, with increased risk in dogs with predisposing factors for GI bleeding.²

• In this prospective study of clinically healthy dogs with a relatively high frequency of administration, risk appeared higher with ketorolac than diclofenac. Diclofenac may therefore be preferable, particularly in dogs with a history of GI disease or smaller dogs that may be exposed to a comparatively higher dose.¹ The lowest possible administration frequency to control clinical ophthalmic signs should be prescribed.

• Pet owners should be taught to monitor for nonophthalmic signs that may indicate GI upset. If signs develop, medication should be discontinued and medical evaluation advised.