Metronidazole Risks

Justine A. Lee, DVM, DACVECC, DABT, VETgirl, LLC

ArticleLast Updated September 20142 min readPeer 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)

    • Hepatotoxicity<sup1,2 sup> 

    • 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.