Abstract

Meloxicam, a non-steroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase-mediated prostaglandin synthesis, is widely used in veterinary medicine.³ Adverse effects, including gastrointestinal ulceration, hepatotoxicity, and nephrotoxicity, occur in multiple species.^2,4,5

Three adult female California sea lions (CSLs) undergoing rehabilitation for domoic acid toxicosis developed nephrotoxicity following treatment with multiple doses of meloxicam (approximately 0.1 mg/kg PO or IM, once-daily) after 10+ days in care because of secondary ailments (corneal ulcers [n=2] and rectal prolapse [n=1]). They initially improved, but two developed severe azotemia after 6–7 days of meloxicam treatment. One died, and the other was euthanized following clinical deterioration. The third was euthanized due to recurrence of neurologic deficits, and azotemia was noted on blood collected immediately before euthanasia. On necropsy, all three had diffuse renal pallor with pale, granular papillae. Two had numerous hemorrhagic gastric ulcers. One also had an accentuated reticular pattern throughout the liver. All three had hippocampal atrophy consistent with domoic acid toxicity. Serum meloxicam concentrations obtained for one of two patients approximately 96 hours after treatment was higher than expected for that post-administration time point.⁶ Serology for leptospirosis was negative, and the gross renal abnormalities were presumptively attributed to meloxicam. Histopathology was pending at the time of abstract submission.

This is the first report of meloxicam-associated nephrotoxicity in pinnipeds. While multiple factors such as hydration, nutrition, other medication, and/or compromised immune function may have contributed to the development of nephrotoxicity, further evaluation of the nephrotoxic effects of domoic acid, documented in mice,² is warranted in CSLs².

Acknowledgments

The authors thank the animal care staff, veterinarians, veterinary technicians, and volunteers at The Marine Mammal Center who facilitated the treatment of these patients, as well as Barbie Halaska, Jackie Isbell, Carlos Rios, and Jennifer Soper for assisting with post-mortem examination, sampling, and clinical pathology analysis.

*Presenting author
+Student presenter

Literature Cited

1.  Burukoglu D, Baycu C, Taplamacioglu F, Sahin E, Bektur E. Effects of nonsteroidal anti-inflammatory meloxicam on stomach, kidney, and liver of rats. Toxicology and Industrial Health. 2016;32(6):980–986.

2.  Funk JA, Janech MG, Dillon JC, Bissler JJ, Siroky BJ, Bell PD. Characterization of renal toxicity in mice administered the marine biotoxin domoic acid. Journal of the American Society of Nephrology. 2014;25(6):1187–1197.

3.  Papich MG. Papich Handbook of Veterinary Drugs. St. Louis, MO: Saunders; 2020:565–568.

4.  Rivera-Velez SM, Broughton-Neiswanger LE, Suarez MA, Slovak JE, Hwang JK, Navas J, Leung AWS, Pineyro PE, Villarino NF. Understanding the effect of repeated administration of meloxicam on feline renal cortex and medulla: a lipidomics and metabolomics approach. Journal of Veterinary Pharmacology and Therapeutics. 2019;42(4):476–486.

5.  Ross K, Le-Bert C, Ix JH, Ardente A, Stacy N, Jensen E. Treatment of acute kidney injury following meloxicam administration in an Atlantic bottlenose dolphin (Tursiops truncatus). In: IAAAM 2022 Conference Proceedings.

6.  Trumbull E, Papich MG, Rivard M, Peters M, Field C. Comparative pharmacokinetics of a single dose of meloxicam in the California sea lion (Zalophus californianus) and Pacific harbor seal (Phoca vitulina richardii). 2022. [Manuscript in preparation].