| VITAMIN B6|
|Pharmacology: Vitamin B6 is a water soluble B complex vitamin which is present in many foods as pyridoxine, pyridoxal and pyridoxamine. These forms of vitamin B6 are converted in vivo to pyridoxal phosphate and pyridoxamine phosphate, which are essential coenzymes in the metabolism of certain amino acids such as tryptophan, in carbohydrate and lipid metabolism, and in the synthesis of heme and GABA, an inhibitory neurotransmitter.
Vitamin B6 deficiency is characterized by seizures, seborrheic dermatitis, glossitis, nausea and vomiting, and dizziness. There is also accumulation and urinary excretion of xanthurenic acid (an intermediary metabolite of tryptophan), which may be measured to aid in diagnosing vitamin B6 deficiency. Certain drugs can act as vitamin B6 antagonists, leading to secondary deficiency. These include hydrazines (e.g., isoniazid), cycloserine, pyrazinamide and penicillamine.
A hereditary vitamin B6 dependency syndrome, in which large amounts are needed to prevent seizures, has been seen in infants in whom an apoenzyme for glutamic acid decarboxylase with decreased vitamin B6 binding capacity leads to deficient production of GABA. Other vitamin B6-responsive conditions have been identified such as a hereditary sideroblastic anemia and certain metabolic disorders caused by genetic abnormalities (e.g., xanthurenic aciduria, cystathioninuria, hyperoxaluria and homocystinuria).
Vitamin B6 requirements are increased in pregnancy and lactation and in patients taking estrogens (e.g., oral contraceptives).
Pharmacokinetics: Pyridoxine, pyridoxal and pyridoxamine are readily absorbed from the gastrointestinal tract, converted to the active forms of vitamin B6 and stored in the liver and brain. Total body stores amount to 16 to 27 mg. Vitamin B6 is metabolized in the liver and excreted in the urine.
Vitamin B6 crosses the placenta and is excreted in breast milk.
Indications: In the prevention and treatment of vitamin B6 deficiency. Vitamin B6 is also used in the management of acute isoniazid overdosage.
Contraindications: Hypersensitivity to vitamin B6 or any component of a vitamin B6-containing pharmaceutical preparation.
Precautions: Vitamin B6 is relatively nontoxic in usual doses. However, chronic administration of high doses (e.g., 2 g or more daily for several months) has led to sensory neuropathy.
Drug Interactions : Vitamin B6 increases the peripheral metabolism of levodopa. When levodopa is combined with carbidopa, this effect is prevented.
Isoniazid, cycloserine, pyrazinamide and penicillamine may antagonize the effects of vitamin B6 and lead to a secondary deficiency.
Patients taking estrogens (e.g., oral contraceptives) have higher vitamin B6 requirements.
Pregnancy: No adverse effects have been reported with the use of physiologic doses of vitamin B6 during pregnancy. However, the use of high doses during pregnancy has been implicated in some cases of vitamin B6 dependent syndrome in infants (see Pharmacology).
Lactation: Vitamin B6 is excreted in breast milk; however, adverse effects have not been reported with the use of physiologic doses of vitamin B6 during lactation.
Adverse Effects: Nausea, headache, paresthesia, somnolence and low serum folic acid concentrations have been reported. Sensory neuropathy can occur following long-term administration of large doses (2 g or more daily for 2 months or longer).
Transient dependency symptoms may occur upon withdrawal of vitamin B6 therapy at a dose of 200 mg/day for 33 days. The significance of this is unknown; however, for patients on large doses for long periods of time, withdrawal of vitamin B6 should probably be gradual.
Temporary burning or stinging and pain may be experienced at the site of s.c. or i.m. injection.
Dosage: In the prevention of vitamin deficiencies, adequate dietary intake is preferred over supplementation whenever possible. For information on food sources of vitamin B6, see Vitamin Food Sources in the Clin-Info section.
For a listing of the daily requirements of vitamin B6 and other nutrients, see Recommended Nutrient Intake in the Clin-Info section. Patients taking isoniazid, cycloserine, pyrazinamide, penicillamine or oral contraceptives may require higher daily intake. Requirements are also higher during pregnancy and lactation, and in patients with xanthurenic aciduria, hyperoxaluria, cystothioninuria or homocystinuria.
Vitamin B6 is usually administered orally; however, it can be given by i.v., i.m. or s.c. injection when the oral route is not possible.
Treatment of Deficiency: 2.5 to 10 mg daily in adults. Once the clinical signs of deficiency have been corrected, the dose may be reduced to 2 to 5 mg daily for several weeks.
Vitamin B6 Dependency in Infants: For the treatment of seizures in these infants, a single dose of 10 to 100 mg vitamin B6 i.m. or i.v. has been recommended. Seizures usually stop within 2 to 3 minutes. Some infants may require lifelong supplementation with oral doses of 2 to 100 mg.
Hereditary Sideroblastic Anemia: An oral dose of 200 to 600 mg daily has been suggested. Lifelong supplementation may be required to prevent recurrence.
Treatment of Isoniazid Overdosage: For the treatment or prevention of seizures or coma following isoniazid poisoning, a dose of vitamin B6 equal to the amount of isoniazid ingested is given by i.v. injection. Alternatively, if the amount ingested is unknown, a dose of 5 g vitamin B6 may given i.v. initially and repeated at 30-minute intervals until seizures are controlled.