isoniazid overdose

introduction

isoniazid (INH) is a antibiotic medication used to Rx tuberculosis (TB)
isoniazid toxicity causes seizures usually within 1hr post-ingestion, but may occur 30min to 5hrs post-ingestion
ingestion of 80-150mg/kg is associated with severe toxicity and significant mortality unless treated
doses as little as 1.5g ingested acutely may cause toxicity in adults
isoniazid has a serum half-life of 1 – 4 hours

isoniazid binds to pyridoxine and also inhibits pyridoxine phoshokinase, both effects result in reduced production of pyridoxl 5 phosphate which is an important cofactor for the production of GABA from glutamic acid

resus area
ABC's
usual Rx of seizures is not as effective as for other causes of seizures although benzodiazepines are synergistic with pyridoxine in controlling seizures

pyridoxine (vitamin B6) prevents a decrease in CNS GABA and helps prevent and Rx seizures due to isoniazid toxicity

acute isoniazid ingestion:
- isoniazid ingestion > 80mg/kg even if asymptomatic
- generalised, protracted seizures that are unresponsive to standard anticonvulsant therapy
- coma

pyridoxine is available as 100mg in 2mL ampoules
- pyridoxine injection is only available in Australia via the Special Access Scheme (SAS). The medical officer must complete a SAS Category A form, fax it to Pharmacy and file the original in the patient’s medical history.
administer the infusion in 5% glucose at 0.5g/minute until the infusion is complete
dose of pyridoxine:
- 1g pyridoxine per 1g isoniazid ingested up to max. 5g, or,
- if amount ingested unknown, give 5g (50 ampoules) in adults or 70mg/kg in children

pyridoxine toxicity may cause:
- reversible sensory axonal neuropathy and perhaps CNS effects, although this is usually following chronic high doses of 0.2-6g per day for months
- irreversible destruction of sensory ganglion cells (neuronopathy) may also occur after a single extremely large parenteral dose