Metronidazole typically has a wide margin of safety in small animals; on occasion, however, toxicity can be an issue, along with other infrequent adverse events.
- Although a rare occurrence, animals may be hypersensitive to metronidazole; therefore, its use should be avoided in patients with sensitivity to any nitroimidazole derivative.1,2
- Adverse events are uncommon but have been reported, including
- CNS signs/neurotoxicity (eg, ataxia, peripheral neuropathy, hypermetric gait, nystagmus, head tilt, seizures)1-3
- GI signs (eg, vomiting, stomatitis, glossitis, diarrhea1,2; anorexia, hypersalivation likely due to bitter and/or sharp metallic taste2)
- Because glucuronidation is deficient in cats, they may be more sensitive to metronidazole; high doses should thus be avoided.
High doses should be avoided in cats, as this species may be more sensitive to the effects of metronidazole.
- Metronidazole toxicity can occur in dogs and cats but typically involves chronic versus acute exposure.
- Chronic doses >62 mg/kg q24h have been associated with toxicity.1,2
- Severe permanent neurologic signs may be seen with large, acute doses (>250 mg/kg).1,2
- Signs of toxicity typically include
- Vestibular signs1-3
- Conscious proprioceptive deficits
- Head tilt
Diagnosis & Treatment
- Administration of IV diazepam may be useful in definitive diagnosis of metronidazole toxicity, aiding in the transient, acute improvement in clinical signs.1,2,4
- Immediate discontinuation of metronidazole, symptomatic and supportive care (eg, fluid therapy, antiemetic therapy), and diazepam therapy is advised.1,2,4
- Resolution can be seen within 14 days after drug therapy has been discontinued.2
- Diazepam therapy
- In dogs only
- Can decrease duration of clinical signs from 4.25 days in untreated dogs to 13.4 hours in treated dogs4
- 0.43 mg/kg PO q8h for 3 days2,4
- Warning for cats
- PO diazepam should not be used as treatment of metronidazole toxicity in cats because of risk for acute hepatic necrosis secondary to benzodiazepines.
- IV administration can, however, be used to aid in the diagnosis of metronidazole toxicity.
1. Plumb’s Veterinary Drug Handbook, 7th ed. Plumb DC (ed)—Ames: Wiley– Blackwell, 2011, pp 682-685.
2. Metronidazole. Fitzgerald KT. In Small Animal Toxicology, 3rd ed—St. Louis: Saunders Elsevier, pp 653-658, 2013.
3. Central nervous system toxicosis associated with metronidazole treatment of dogs: Five cases (198 -1987). Dow SW, LeCouteur RA, Poss ML, et al. JAVMA 195:365-368, 1989.
4. Diazepam as a treatment for metronidazole toxicosis in dogs: A retrospective study of 21 cases. Evans J, Levesque D, Knowles K, et al. JVIM 17:304-310, 2003.
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