Metronidazole is used in veterinary medicine in the treatment of several infections, including giardiasis, anaerobic infections, and inflammatory bowel disease. Adverse effects of this drug in dogs include vomiting, hepatotoxicity, neutropenia, and neurologic signs. Neurologic toxicity has been reported in dogs receiving >60 mg/kg/d for an average of 3 to 14 days, as well as lower doses. The recommendation is to discontinue the treatment, with reported recovery times of 1 to 2 weeks. This study compared dogs that were treated with supportive care and diazepam (initial bolus given IV and then PO every 8 hours for 3 days) with dogs that received only supportive care. Dogs treated with diazepam had an average response time of 13 hours and an average recovery time of 38.7 hours. The dogs that were not treated with diazepam had an average response time of 4.25 days and an average recovery time of 11.6 days.

The exact mechanism of metronidazole toxicity is not known, nor is it known why diazepam is effective in treating the toxicity. It may be related to the modulation of the γ-aminobutyric acid receptor within the cerebellar and vestibular systems.

COMMENTARY: This article presents an alternative for treating metronidazole toxicosis that greatly reduces both response time and recovery time. Although this problem is uncommon, we have not had a good alternative for treatment in the past.

Diazepam as a treatment for metronidazole toxicosis in dogs: a retrospective study of 21 cases. Evans J, Levesque D, Knowles K, Longshore R, Plummer S. ACVIM PROCEEDINGS, 2003, pp 304-310.