DESCRIPTION

Pyridoxine is a water-soluble B-complex vitamin that is an essential cofactor in many enzymatic reactions.

FORMS AND USES

• Pyridoxine is available in tablets (Beelith, Lurline PMS, Marlyn Formula, Mega-B, Aminoxin, Apatate) or in injection form at a concentration of 100 mg/ml.
• Pyridoxine is used for treatment of seizure associated with isoniazid (INH), Gyromitra mushroom [monomethylhydrazine (MMH)], or penicillamine poisoning.
• Pyridoxine is also used prophylactically to prevent development of peripheral neuropathy in patients taking INH.
• In ethylene glycol intoxication, pyridoxine therapy has been proposed to reduce levels of toxic metabolites.

MECHANISM OF ACTION

• Pyridoxine (after conversion to pyridoxal phosphate) is required for the synthesis of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter of the CNS. A decreased level of GABA is believed to cause seizures due to loss of neural inhibition.
• INH and MMH interfere with the synthesis of pyridoxal phosphate, leading to a functional pyridoxine deficiency.
• As pyridoxine levels decrease, GABA production declines and seizure activity or coma may ensue.

DRUG AND DISEASE INTERACTIONS

• Pyridoxine levels can be depleted by penicillamine, cycloserine, and hydralazine.
• Pyridoxine enhances peripheral decarboxylation of levodopa, reducing its effectiveness against Parkinson's disease.

PREGNANCY AND LACTATION

• Pregnant women receiving INH should be given 25 mg/day of pyridoxine as prophylaxis against peripheral neuritis.
• Used as a vitamin within recommended daily allowance. US FDA Pregnancy Category A. Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester, and the possibility of fetal harm appears remote.
• High-dose use. US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

SEIZURES OF UNKNOWN CAUSE

INH or Gyromitra mushroom ingestion may be unrecognized; if patient does not respond to initial anticonvulsant therapy, pyridoxine should be administered.

KNOWN INGESTION OF INH

• In cases of suicidal ingestion of INH, prophylactic treatment before onset of seizure is recommended.
• Any INH ingestion associated with seizures should be treated with pyridoxine.

ETHYLENE GLYCOL TOXICITY

• Pyridoxine should be considered in the treatment of patients who have ingested ethylene glycol.
• Pyridoxine (and thiamine) are adjuncts to ethanol therapy and may reduce production of oxalic acid, a toxic metabolite of ethylene glycol.

MMH TOXICITY

• Ingestion of Gyromitra species of mushroom can produce seizures and should be treated with pyridoxine.

PENICILLAMINE-INDUCED SEIZURES

• Pencillamine-induced seizures have been reported to respond to pyridoxine 100 mg intravenously.

Section Outline:

• SEIZURES OF UNKNOWN CAUSE
• KNOWN INGESTION OF INH
• ETHYLENE GLYCOL TOXICITY
• MMH TOXICITY
• PENICILLAMINE-INDUCED SEIZURES

Patients with known hypersensitivity reaction to pyridoxine.

ADVERSE EFFECTS

• Acute and or repeated supratherapeutic doses of pyridoxine have been associated with peripheral sensory neuropathy.
  • Although the maximum nontoxic pyridoxine dose is unknown, acute single doses up to 10 to 15 g are well tolerated.
  • In general, unless massive INH ingestion has occurred, the maximum pyridoxine dose is 10 to 15 g.
• Large, acute overdose of pyridoxine (5 g/kg) may cause tachypnea, postural hypotension, paralysis, or seizures.

SEIZURES OF UNKNOWN CAUSE

• Benzodiazepines should be administered initially.
• If seizures continue, 5 g of pyridoxine can be given intravenously over 10 minutes.
• Dose should be repeated in 30 minutes if needed for control of seizures.

KNOWN INGESTION OF INH

• In cases of suicidal ingestion of INH (unknown dose), 5 g of pyridoxine should be administered intravenously over 30 minutes.
• The pediatric dose is 70 mg/kg up to 5 g.
• When the amount of INH ingested is known and seizures or coma have occurred:
  • The maximum total amount of INH that could have been ingested should be calculated.
  • An equal amount of pyridoxine should be administered (e.g., if 10 tablets of 300 mg INH were ingested, patient should receive 3 g of pyridoxine) intravenously over 10 minutes.
  • Pediatric dosage. The pyridoxine administered should be based on the amount of INH ingested, not the weight of the patient.
  • Dose should be repeated in 15 to 30 minutes if seizures persist or recur.
• When the amount of INH ingested is unknown and seizures or coma have occurred:
  • The patient should receive 5 g of pyridoxine intravenously over 10 minutes.
  • Dose should be repeated in 15 to 30 minutes if seizures persist or recur.

ETHYLENE GLYCOL TOXICITY

• The adult dose is 50 to 100 mg pyridoxine intravenously every 6 hours until the ethylene glycol level is undetectable.
• The pediatric dose is 1 to 2 mg/kg every 6 hours until their ethylene glycol level is undetectable.
• The dose should be repeated after dialysis unless the ethylene glycol level is less than 20 mg/dl.

MMH TOXICITY

• Patients with coma or seizures from MMH should have 25 mg/kg pyridoxine administered intravenously over 10 minutes to a maximum dose of 10 g.

Section Outline:

• SEIZURES OF UNKNOWN CAUSE
• KNOWN INGESTION OF INH
• ETHYLENE GLYCOL TOXICITY
• MMH TOXICITY

• If no parenteral form of pyridoxine is available, pyridoxine tablets may be crushed and mixed with water to form a slurry, which should be administered orally or via an endo-gastric tube in a gram-for-gram dose for each gram of INH ingested, or according to above doses for MMH and ethylene glycol toxicities.
• Pyridoxine should be used in conjunction with a benzodiazepine for the synergistic effect exerted to control seizures induced by INH.
• If seizures are refractory to repeated dosing with pyridoxine and benzodiazepine, a loading dose of phenobarbital should be considered, possibly followed by neuromuscular blockade and general anesthesia (including endotracheal intubation).
• Seizures that remain unresponsive to high doses of pyridoxine may not be due to INH or MMH toxicity.
• Careful attention must be directed to the consideration of other potential causes of seizure in refractory patients (hypoxia, hypoglycemia, or other poisons).

Poisoning by anticonvulsants and antiparkinsonism drugs.

See Also: SECTION IV, Ethylene Glycol, Isoniazid, and Mushrooms chapters.

RECOMMENDED READING

Wason S, Lacouture PG, Lovejoy FH. Single high dose pyridoxine treatment for isoniazid overdose. JAMA 1981;246:1102-1104.

Author: Mark C. Goodman

Reviewer: Luke Yip