Isoniazid Poisoning

Aka: Isoniazid Poisoning, Isoniazid Overdose, Isoniazid Toxicity

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II. Pharmacokinetics

  1. Absorption rapid
  2. Peak levels: 1 to 2 hours (up to 6 hours in Overdose)
  3. Toxic Levels: >20 mg/kg
  4. Hepatic metabolism (rate via NAT2 has high genetic variability, up to 6x)

III. Mechanism: Toxicity

  1. Pyridoxine Deficiency
  2. Glutamic Dehydrogenase inhibition
    1. Blocks conversion of Glutamate to GABA
    2. Results in GABA deficiency

IV. Symptoms

  1. Nausea
  2. Vomiting
  3. Hyperthermia
  4. Hypotension
  5. Altered Mental Status
  6. Ataxia
  7. Acute Kidney Injury
  8. Seizures or Status Epilepticus
    1. Ingestions >20 mg/kg (and esp. >40 mg/kg)
  9. Rhabdomyolysis

V. Labs

  1. See Unknown Ingestion for broad based lab evaluation after ingestion
  2. INH level
    1. Level >10 mg/L at 1 hour of ingestion suggests acute toxicity
  3. Labs in isolated Isoniazid ingestion
    1. Bedside Glucose
    2. Basic metabolic profile
      1. Anion Gap Metabolic Acidosis
    3. Creatinine Phosphokinase

VI. Imaging

  1. CT Head
    1. Consider in unknown cause of Altered Level of Consciousness or Status Epilepticus

VII. Diagnostics

  1. Electroencephalogram (EEG) monitoring
    1. Indicated in persistant or recurrent Seizures

VIII. Management

  1. Decontamination
    1. Activated Charcoal 1 g/kg if presenting within one hour of ingestion, and airway protected
    2. Consider Hemodialysis if started early in large ingestions
  2. Pyridoxine
    1. Give same dose of Pyridoxine of the Isoniazid ingestion if known OR
    2. Pyridoxine 70 mg/kg (up to 5 g) IV over 3 to 5 minutes
    3. May repeat dosing for recurrent Seizures
  3. Seizures
    1. See Status Epilepticus
    2. Lorazepam 0.5 to 1 mg/kg (up to 2 mg/dose) as needed
    3. Phenobarbital
  4. Disposition
    1. Observe or admit all patients with recurrent Seizures or persistent Altered Mental Status
    2. May discharge after 4 to 6 hours following ingestion if asymptomatic
  5. Hemodialysis
    1. Refractory Seizures and Pyridoxine not available

IX. References

  1. Tomaszewski (2018) Crit Dec Emerg Med 32(7):28

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