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INTRODUCTION

  1. Pharmacology. Pyridoxine (vitamin B6) is a water-soluble B-complex vitamin that acts as a cofactor in many enzymatic reactions. Overdose involving isoniazid or other hydrazines (eg, Gyromitra mushrooms, rocket propellant, or fuel-containing hydrazine, mono-, or di-methylhydrazine) may cause seizures by interfering with pyridoxine utilization in the brain, and pyridoxine given in high doses can control these seizures rapidly and may hasten consciousness. It can also correct the lactic acidosis secondary to isoniazid-induced impaired lactate metabolism. In ethylene glycol intoxication, pyridoxine may enhance metabolic conversion of the toxic metabolite glyoxylic acid to the nontoxic product glycine. Pyridoxine is well absorbed orally but usually is given intravenously for urgent uses. The biological half-life is about 15–20 days.

  2. Indications

    1. Acute management of seizures caused by intoxication with isoniazid, hydrazines, Gyromitra mushrooms, or possibly cycloserine. Pyridoxine may act synergistically with diazepam.

    2. Adjunct to therapy for ethylene glycol intoxication.

    3. May improve dyskinesias induced by levodopa.

  3. Contraindications. Use caution in patients with known sensitivity to pyridoxine or parabens preservative.

  4. Adverse effects

    1. Usually no adverse effects are noted from acute dosing of pyridoxine.

    2. Chronic excessive doses may result in peripheral neuropathy.

    3. Use of the 1-mL vials may cause mild CNS depression owing to the preservative if 50 or more vials (to deliver ≥5 g of pyridoxine) are administered (equivalent to ≥250 mg of chlorobutanol).

    4. Preparations containing the preservative benzyl alcohol (eg, contained in some 1-mL and the 30-mL vials) have been associated with "gasping" syndrome in premature infants.

    5. Use in pregnancy. FDA Category A (Introduction). However, chronic excessive use in pregnancy has resulted in pyridoxine withdrawal seizures in neonates.

  5. Drug or laboratory interactions. No adverse interactions are associated with acute dosing.

  6. Dosage and method of administration

    1. Isoniazid poisoning. Give 1 g of pyridoxine intravenously for each gram of isoniazid known to have been ingested (as much as 52 g has been administered and tolerated). Dilute in 50 mL of dextrose or saline and give over 5 minutes (rate of 1 g/min). If the ingested amount is unknown, administer 4–5 g IV empirically and repeat every 5–20 minutes as needed.

    2. Hydrazine and gyromitra mushroom poisoning. Give 25 mg/kg IV over 15–30 minutes for seizures; repeat as necessary and up to a maximum cumulative dose of 15–20 g daily has been suggested for mushroom poisoning.

    3. Ethylene glycol poisoning. Give 50 mg IV or IM every 6 hours until intoxication is resolved.

    4. Cycloserine poisoning. A dosage of 300 mg/d has been recommended.

  7. Formulations

    1. Parenteral. Pyridoxine hydrochloride (various), 100 mg/mL (10% solution) in 1- and 30-mL vials (1-mL vial may contain the preservative chlorobutanol, and 30-mL vial contains 1.5% benzyl alcohol). Note: Only one US company, Legere Pharmaceuticals (Scottsdale, AZ; phone: 1-800-528-3144), manufactures and distributes the 3-g (30-mL) vials. See "Adverse effects" above regarding use of the 1-mL vials.

    2. Suggested minimum stocking levels to treat a 100-kg adult for the first 8 hours and 24 hours: pyridoxine hydrochloride, first 8 hours: 9 g or three vials ...

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