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Metronidazole Risks

Metronidazole Risks

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

Pharmacology & Medications

|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

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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