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655.e2 Metronidazole Toxicosis

Metronidazole Toxicosis
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• Common dosage errors (and therefore risk
BASIC INFORMATION
of toxicosis): (CNS), disrupting inhibitory neurotransmis-
sion. Diazepam is presumed to have a greater
Definition ○ Prescribing the high enteric dosage for affinity for the benzodiazepine site and may
Neurologic dysfunction due to administration > 1 week competitively antagonize the binding of
of high dosages of metronidazole ○ Overlooking the divided q 12h indication metronidazole to the GABA receptor.
and prescribing the high enteric dosage q
Synonyms 12h Recommended Monitoring
Flagyl toxicosis, metronidazole-induced ○ Failing to reduce the dosage in patients • Clinical response to discontinuation of
encephalopathy with liver disease metronidazole
○ Failing to accurately divide the 250-mg • Deterioration or worsening of clinical signs
Epidemiology tablets for cats or very small dogs, where should prompt evaluation for another
SPECIES, AGE, SEX small differences in tablet fractions cor- diagnosis.
Dogs and cats of any age and either sex can respond to relatively large excesses in
be affected. dosage per kg of body weight PROGNOSIS & OUTCOME
RISK FACTORS DIAGNOSIS The prognosis is excellent with prompt with-
Acute toxicosis is usually associated with drawal of the offending drug. Most patients
dosages of 60 mg/kg/day; chronic toxicosis Diagnostic Overview show improvement within 48 hours, although
with dosages of 12-30 mg/kg/day for 1 week The diagnosis is based on medication history, it can take a week for complete resolution.
or longer. Coadministration of cimetidine may physical signs, and resolution of signs after
increase risk. discontinuing the drug. PEARLS & CONSIDERATIONS
Clinical Presentation Differential Diagnosis Comments
HISTORY, CHIEF COMPLAINT • Encephalitis Clinicians should consider metronidazole
• Initial signs in dogs are anorexia and • Neoplasia toxicosis in any patient developing neurologic
intermittent vomiting that progress rapidly signs while taking this drug. With prompt
to generalized ataxia. Seizures and head tilt Initial Database recognition and withdrawal of the offending
are less common. Routine laboratory tests are usually normal, but drug, complete recovery is expected.
• Cats suffer a sudden onset of weakness and mild elevations in liver enzymes are possible.
disorientation, often with seizures. Prevention
Advanced or Confirmatory Testing Avoid dosages of metronidazole higher than 30
PHYSICAL EXAM FINDINGS Diagnosis is based on clinical features, history mg/kg/day. Some published dosages are high
• Affected dogs typically show severe gen- of metronidazole administration, and recovery enough to cause toxicosis.
eralized ataxia, depression, and vertical after drug discontinuation.
nystagmus. Paraparesis, tetraparesis, head Technician Tips
tilt, and tremor are less common. TREATMENT Ask the owner specifically about metronidazole
• Affected cats often show ataxia with postural use in patients presenting with ataxia.
reaction deficits in all limbs, depression or Treatment Overview
stupor, seizures, and blindness with intact The goal of treatment is to stop metronidazole SUGGESTED READING
pupillary light reflexes. administration and provide supportive care until Evans J, et al: Diazepam as a treatment for metro-
the signs resolve, usually within 3-5 days. nidazole toxicosis in dogs: a retrospective study
Etiology and Pathophysiology of 21 cases. J Vet Intern Med 17:304-310, 2003.
• The cumulative dosage can be important Acute General Treatment
because higher doses generally require shorter • Discontinue the metronidazole. ADDITIONAL SUGGESTED
duration of administration to cause toxic- • Provide parenteral hydration and nutrition READINGS
ity. However, there seems to be substantial if necessary. Caylor KB, et al: Metronidazole neurotoxicosis in two
individual susceptibility to toxicosis. • Give antiseizure medication such as diazepam cats. J Am Anim Hosp Assoc 37:258-262, 2001.
• Metronidazole is recommended for two dif- as needed. Dow SW, et al: Central nervous system toxicoses
ferent indications in many drug formularies: • Administration of oral diazepam 0.5 mg/kg associated with metronidazole treatment of dogs:
at an enteric dosage for acute gastrointestinal q 8h may speed recovery in dogs, including five cases (1984-1987). J Am Vet Med Assoc
infections and parasitoses (30-50 mg/kg those that are not showing seizure activity. It 195:365-368, 1989.
divided q 12h for 5-7 days) or at dosages for is postulated that signs of toxicity result from Tauro A, et al: Metronidazole-induced neurotoxicity
anaerobic bacterial infections (10-15 mg/kg metronidazole binding to the benzodiazepine in 26 dogs. Aust Vet J 96:495-501, 2018.
PO q 12h for days to weeks; lowered to 7.5 site on gamma-aminobutyric acid (GABA) AUTHOR: William B. Thomas, DVM, MS, DACVIM
mg/kg PO q 12h for hepatic dysfunction). receptors in the central nervous system EDITOR: Karen R. Muñana, DVM, MS, DAVCIM

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