September 2014
Peer Reviewed

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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.

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
    • Neutropenia1,2
    • GI signs (eg, vomiting, stomatitis, glossitis, diarrhea1,2; anorexia, hypersalivation likely due to bitter and/or sharp metallic taste2)
    • Hepatotoxicity1,2 
    • Pigmenturia1,2
  • 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.

Toxicities

  • 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

Clinical Signs

  • Signs of toxicity typically include
    • Ataxia1-3
    • Vestibular signs1-3
    • Nystagmus1-3
    • Conscious proprioceptive deficits
    • Head tilt 
    • Tremors 
    • Seizures

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.
References and author information Show
References

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.

Author

Justine A. Lee

DVM, DACVECC, DABT VetGirl

Justine A. Lee, DVM, DACVECC, DABT, is the CEO and founder of VetGirl, a subscription-based podcast service offering RACE-approved continuing education (CE). Dr. Lee graduated from Cornell University and completed her internship at Angell. She also completed an emergency fellowship and residency at University of Pennsylvania. Dr. Lee is double-boarded in both emergency critical care and toxicology. In 2011, she was named the NAVC Conference Small Animal Speaker of the Year, and she is passionate about delivering clinically relevant CE.

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