Metronidazole Risks

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

  • Neutropenia^1,2

  • GI signs (eg, vomiting, stomatitis, glossitis, diarrhea^1,2; anorexia, hypersalivation likely due to bitter and/or sharp metallic taste2)

  • Hepatotoxicity<sup1,2 sup> 

  • Pigmenturia^1,2

• Because glucuronidation is deficient in cats, they may be more sensitive to metronidazole; high doses should thus be avoided.

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

  • Ataxia^1-3

  • Vestibular signs^1-3

  • Nystagmus^1-3

  • 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 days^2,4

  • 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.