Pyridoxine
Related FACEM curriculum (2022) learning objectives:
- ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
- ME 3.8.2.4 Identify the appropriate antidote or antivenom.
Toxicological Indications
- Metabolic acidosis and seizures caused by hydrazine compounds (isoniazid, Gyromitra mushrooms, hydrazine from jet and rocket fuels).
- Adjunctive therapy in ethylene glycol toxicity.
Contraindications
- Known hypersensitivity.
Mechanism of Action
- Active form: Pyridoxal 5-phosphate (P5P), a cofactor in over 100 enzymatic reactions.
- Critical for converting L-glutamic acid to GABA.
- Hydrazines (e.g., isoniazid) inhibit P5P formation, bind and inactivate existing P5P, and enhance its elimination.
- GABA depletion leads to CNS excitation and seizures.
- Large pyridoxine doses restore normal GABA concentrations and activity.
Pharmacokinetics
- Oral bioavailability ~50%; volume of distribution 0.6 L/kg.
- Rapid metabolism to active phosphate ester at extrahepatic sites.
Administration
- Place patient in a monitored area with full resuscitation facilities.
- EEG monitoring required if the patient is intubated and paralysed.
Isoniazid Overdose
- Initial dose: 1 g pyridoxine per gram of isoniazid ingested (max 5 g; 70 mg/kg in children).
- Administer as a slow IV infusion at 0.5 g/min until seizures stop or infusion completes.
- Remaining dose: Infuse over 4 hours.
- If ingested dose is unknown, give 5 g empirically.
- Administer benzodiazepines concurrently for synergistic seizure control.
Hydrazine or Monomethylhydrazine Poisoning
- Initial bolus: 25 mg/kg IV.
Ethylene Glycol Poisoning
- Dose: 50 mg IV every 6 hours.
Therapeutic Endpoints
- Seizure control.
Adverse Drug Reactions
- Chronic high oral doses may cause peripheral neuropathy (not observed with acute dosing in isoniazid overdose).
Specific Considerations
- Pregnancy: No restrictions.
- Paediatrics: No restrictions.
Handy Tips
- Pyridoxine is often available only in 50 mg vials; large quantities (e.g., 100 vials) may be required for isoniazid poisoning.
- If full doses are unavailable, use all available pyridoxine with high-dose benzodiazepines as interim therapy.
- Always administer benzodiazepines with pyridoxine due to synergistic effects on seizure control.
Pitfall
- Failure to administer benzodiazepines concurrently.
Controversies
- Limited human experience in isoniazid poisoning, primarily from case reports. Severe toxicity may respond to supportive care and high-dose benzodiazepines alone.
- Utility of pyridoxine in ethylene glycol poisoning remains uncertain.