Isoniazid, seizures, and pyridoxine

May 26, 2010, 1:48 am

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Isoniazid-Induced Status Epilepticus in a Pediatric Patient After Inadequate Pyridoxine Therapy.  Minns AB et al.  Pediatr Emerg Care 2010;26:380-381.

Abstract

This short case report describes at 0-month-old male infant who ingested up to 2.7 gm of isoniazid (INH).  He had a seizure approximately 45 minutes after ingestion and was treated with pyridoxine (70 mg/kg) and diazepam (1 mg).  Because of continued seizure activity he was given an additional 3 mg diazepam and phenobarbital 20 mg/kg, as well as an additional 2 g pyridoxine.  After this seizure activity ceased and the patient was discharged several days later with good neurological function.

Pyridoxine is an essential co-factor required for the synthesis of GABA, an inhibitory CNS neuromodulator.  INH interferes with the action of pyridoxine, decreasing endogenous GABA.  Treatment for INH overdose is pyridoxine, in the same gram amount as INH ingested.  If the amount ingested  is not known, the recommended initial dose is 5 gm pyridoxine for adults and 70 mg/kg (not to exceed 5 gm) for children.  The key feature of this case is that after receiving 70 mg/kg pyridoxine, the child subsequently received an additional 2 gm.  One of the main points that the authors make is that some texts (they specifically reference Goldfrank’s Toxicologic Emergencies 2006) recommend not exceeding 70 mg/kg pyridoxine in children.  Unfortunately, they misread Goldfrank’s, which says that “Initial doses of pyridoxine in children probably should not exceed 70 mg/kg. These doses are sufficient in the majority of patients, but the dose can be repeated if necessary.” (emphasis mine)  Therefore, their use of more than 70 mg/kg pyridoxine in this case is neither unprecedented nor avant-garde.

In INH toxicity, the dose of pyridoxine can certainly be repeated if necessary.  A benzodiazepine would be expected to have synergistic anti-convulsive effects in this setting, and should be added routinely.  If enough IV pyridoxine is not readily available, the oral preparation can be administered through an NG tube to supplement IV supplies.

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