Dose and Administration

For pyridoxine-dependent seizure control

Diagnostic test

1. 50-100 mg IV, IM.

Maintenance dose

1. 2-100 mg/kg daily PO throughout life.
2. High doses may be required during periods of intercurrent illness.

1. 2-5 mg per day PO.

1. 0.2-0.5 mg per day.

Indications

1. Diagnosis and treatment of pyridoxine-dependent seizures.
2. Prevention and/or treatment of vitamin B6 deficiency.

Contraindications and Precautions

1. Known hypersensitivity to vitamin B6.

Clinical Pharmacology

Pyridoxine-dependent seizures, an autosomal recessive trait, result from a defective binding of pyridoxine to its apoenzyme, glutamate decarboxylase. The apoenzyme catalyses the conversion of glutamic acid to gamma aminobutyric acid (GABA) which acts as an inhibitory neurotransmitter in the central nervous system. Seizure threshold is lowered in infants with reduced concentrations of GABA. Administration of pharmacological doses of pyridoxine will correct the GABA deficiency.

Onset of pyridoxine dependent seizures usually occurs within 4 hours of age. The seizures generally stop within 2-3 minutes following administration of pyridoxine. Discontinuation of pyridoxine results in recurrence of seizures within 1-7 days in the neonate and 2-24 days in the older infant. Therapeutic doses of pyridoxine are virtually without toxicity.

Possible Adverse Effects

1. Venous irritation, soft tissue injury at the IV injection site.
2. Pain, soft tissue injury at the IM injection site.
3. Nausea, headaches, irritability.
4. Profound sedation.

Special Considerations

1. Wherever possible the initial diagnostic administration of pyridoxine should be accompanied by EEG monitoring. There should be a 30 minute period of observation after the test dose for the presence of seizure activity. If seizures persist during the observation period, conventional anticonvulsant therapy should be instituted.
2. Once a definite response to treatment with pyridoxine has been established, therapy should be continued indefinitely.