Pyridoxine (Systemic)


VA CLASSIFICATION
Primary: VT140

Commonly used brand name(s): Beesix; Doxine; Nestrex; Pyri; Rodex; Vitabee 6.

Another commonly used name is
vitamin B 6 .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Nutritional supplement (vitamin)—

antidote (to cycloserine poisoning; to isoniazid poisoning)—
Note: Pyridoxine is a water-soluble vitamin.



Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Pyridoxine deficiency (prophylaxis and treatment)—Pyridoxine is indicated for prevention and treatment of pyridoxine deficiency states. Pyridoxine deficiency may occur as a result of inadequate nutrition or intestinal malabsorption but does not occur in healthy individuals receiving an adequate balanced diet. {05} Simple nutritional deficiency of individual B vitamins is rare since dietary inadequacy usually results in multiple deficiencies. {02} For prophylaxis of pyridoxine deficiency, dietary improvement, rather than supplementation, is advisable. For treatment of pyridoxine deficiency, supplementation is preferred. {25}
—Deficiency of pyridoxine may lead to xanthurenic aciduria, sideroblastic anemia, neurologic problems, seborrheic dermatitis, and cheilosis. {02}
—Recommended intakes may be increased and/or supplementation may be necessary in the following conditions or persons (based on documented pyridoxine deficiency):

• Alcoholism {26}


• Burns


• Congenital metabolic dysfunction— {02}cystathioninuria, {26} homocystinuria, {26} hyperoxaluria, {10} {11} {26} xanthurenic aciduria {26}


• Congestive heart failure {03}


• Fever, chronic


• Gastrectomy


• Hemodialysis {03}


• Hyperthyroidism {03}


• Infants receiving unfortified formulas such as evaporated milk {02}


• Infection


• Intestinal diseases—celiac, diarrhea, {04} regional enteritis, sprue


• Malabsorption syndromes associated with hepatic-biliary tract disease such as alcoholism with cirrhosis {03}


• Stress, prolonged

—Recommended intakes for pyridoxine are related to protein intake. {02} {26}
—Some unusual diets (e.g., reducing diets that drastically restrict food selection) may not supply minimum daily requirements of pyridoxine. Supplementation is necessary in patients receiving total parenteral nutrition (TPN) or undergoing rapid weight loss or in those with malnutrition, because of inadequate dietary intake.
—Recommended intakes for all vitamins and most minerals are increased during pregnancy. Many physicians recommend that pregnant women receive multivitamin and mineral supplements, especially those pregnant women who do not consume an adequate diet and those in high-risk categories (i.e., women carrying more than one fetus, heavy cigarette smokers, and alcohol and drug abusers). {34} Taking excessive amounts of a multivitamin and mineral supplement may be harmful to the mother and/or fetus and should be avoided.
—Recommended intakes for all vitamins and most minerals are increased during breast-feeding. {29}
—Recommended intakes may be increased by the following medications: Cycloserine, {02} ethionamide, hydralazine, {02} immunosuppressants, isoniazid, {01} {26} penicillamine, {02} and estrogen-containing oral contraceptives. {01}
—Some neonates exhibit a hereditary pyridoxine dependency syndrome and require pyridoxine in the first week of life to prevent anemia and mental retardation; the cause is unknown but signs are hyperirritability and epileptiform seizures. {12}

[Cycloserine toxicity (treatment)] or{32}
[Isoniazid toxicity (treatment)]{28}—Pyridoxine is also used as an antidote in cycloserine poisoning and to terminate seizures and prevent neuropathy associated with isoniazid poisoning. {03}

Unaccepted
Pyridoxine has not been proven effective for treatment of acne and other dermatoses, alcohol intoxication, asthma, hemorrhoids, kidney stones, mental disorders, {09} migraine headaches, morning sickness or radiation sickness, premenstrual tension, {06} {07} {08} or for stimulation of lactation or appetite. {03}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    205.64 {33}

Mechanism of action/Effect:

Nutritional supplement—Pyridoxine is converted in erythrocytes to pyridoxal phosphate and to a lesser extent pyridoxamine phosphate, which act as coenzymes for various metabolic functions affecting protein, carbohydrate, and lipid utilization. {02} Pyridoxine is involved in conversion of tryptophan to niacin or serotonin, breakdown of glycogen to glucose-1-phosphate, {01} {04} conversion of oxalate to glycine, {04} synthesis of gamma aminobutyric acid (GABA) within the CNS, and synthesis of heme. {03}

Antidote—Pyridoxine increases the excretion of certain drugs (e.g., cycloserine and isoniazid) that act as pyridoxine antagonists. {02}

Absorption:

The B vitamins are readily absorbed from the gastrointestinal tract, {26} except in malabsorption syndromes. {28} Pyridoxine is absorbed mainly in the jejunum.

Protein binding:

Pyridoxal phosphate—Totally bound to plasma proteins. {03}

Pyridoxine—Not bound to plasma proteins.


Storage:

Pyridoxine is stored mainly in the liver, with lesser amounts stored in muscle and brain. {03}

Biotransformation:

Hepatic. {26}

Half-life:

15 to 20 days. {01} {03}

Elimination:
    Renal (almost entirely as metabolites). {01} {26} Excess beyond daily needs is excreted, largely unchanged, in urine.
    In dialysis—Removed by hemodialysis; {03} dialysis patients should receive increased amounts (100 to 300% of USRDA).


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Problems in humans have not been documented with intake of normal daily recommended amounts. However, exposure to large doses of pyridoxine in utero may result in a pyridoxine dependency syndrome in the neonate. {03}

FDA Pregnancy Category A (parenteral pyridoxine). {01}

Breast-feeding

Problems in humans have not been documented with intake of normal daily recommended amounts. {13} {14}

Pediatrics

Problems in pediatrics have not been documented with intake of normal daily recommended amounts.


Geriatrics


Problems in geriatrics have not been documented with intake of normal daily recommended amounts.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with pyridoxine.

Cycloserine or{19}{26}
Ethionamide or{03}
Hydralazine or{02}{19}{28}
Immunosuppressants, such as:
Azathioprine
Chlorambucil
Corticosteroids
Corticotropin (ACTH)
Cyclophosphamide
Cyclosporine
Mercaptopurine, or
Isoniazid or{01}{02}{26}
Penicillamine{02}{19}{26}    (may cause anemia or peripheral neuritis by acting as pyridoxine antagonists or increasing renal excretion of pyridoxine; recommended intakes for pyridoxine may be increased in patients receiving these medications {02})


Estrogens or{27}
Contraceptives, estrogen-containing, oral{26}{28}    (may increase recommended intakes for pyridoxine {01})


» Levodopa    (concurrent use with pyridoxine is not recommended since levodopa's antiparkinsonian effects are reversed by as little as 5 mg of pyridoxine orally; this problem does not occur with the carbidopa-levodopa combination {01} {02})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Urobilinogen determinations using Ehrlich's reagent    (pyridoxine may produce false-positive results {03})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problem exists
Sensitivity to pyridoxine{01}


Side/Adverse Effects
Doses of 200 mg per day for over 30 days have been reported to produce a pyridoxine dependency syndrome. {01}

High doses of pyridoxine (2 to 6 grams per day) {02} {15} {16} {17} {18} taken for several months have caused a severe sensory neuropathy, progressing from unstable gait and numb feet to numbness and clumsiness of hands. This condition seems to be reversible on withdrawal of pyridoxine, {02} although some residual weakness has been observed.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Pyridoxine (Vitamin B 6) (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Description should include function in the body, signs of deficiency, and unproven uses


Importance of diet
Importance of proper nutrition; supplement may be needed because of inadequate dietary intake

Food sources of pyridoxine; effects of processing

Not using vitamins as substitute for balanced diet

Recommended daily intakes for pyridoxine

Before using this dietary supplement
»   Conditions affecting use, especially:
Sensitivity to pyridoxine

Pregnancy—Use of large doses in pregnancy may cause pyridoxine dependency syndrome in the neonate
Other medications, especially levodopa

Proper use of this dietary supplement

» Proper dosing
Proper administration of extended-release capsule dosage forms: Swallowing whole without crushing, breaking, or chewing; contents of capsule may be mixed with jam or jelly and swallowed without chewing

Proper administration of extended-release tablet dosage forms: Swallowing whole without crushing, breaking, or chewing
Missed dose: No cause for concern because of length of time necessary for depletion; remembering to take as directed

» Proper storage


Side/adverse effects
Signs of potential side effects, especially sensory neuropathy


General Dosing Information
Because of the infrequency of single B vitamin deficiencies, combinations are commonly administered. Many commercial combinations of B vitamins are available.

For parenteral dosage forms only
In most cases, parenteral administration is indicated only when oral administration is not acceptable (for example, in nausea, vomiting, preoperative and postoperative conditions) or possible (for example, in malabsorption syndromes or following gastric resection). {01}

Diet/Nutrition
Recommended dietary intakes for pyridoxine are defined differently worldwide.


For U.S.:
The Recommended Dietary Allowances (RDAs) for vitamins and minerals are determined by the Food and Nutrition Board of the National Research Council and are intended to provide adequate nutrition in most healthy persons under usual environmental stresses. In addition, a different designation may be used by the FDA for food and dietary supplement labeling purposes, as with Daily Value (DV). DVs replace the previous labeling terminology United States Recommended Daily Allowances (USRDAs). {29}



For Canada:
Recommended Nutrient Intakes (RNIs) for vitamins, minerals, and protein are determined by Health and Welfare Canada and provide recommended amounts of a specific nutrient while minimizing the risk of chronic diseases. {31}



Daily recommended intakes for pyridoxine are generally defined as follows: {29}:


Infants and children—
Birth to 3 years of age: 0.3 to 1 mg.

4 to 6 years of age: 1.1 mg.

7 to 10 years of age: 1.4 mg.



Adolescent and adult males—
1.7 to 2 mg.



Adolescent and adult females—
1.4 to 1.6 mg.



Pregnant females—
2.2 mg.



Breast-feeding females—
2.1 mg.


The best dietary sources of pyridoxine include meats, bananas, lima beans, egg yolks, peanuts, and whole-grain cereals. {04} Substantial loss of pyridoxal and pyridoxamine (but not pyridoxine) occurs during cooking.



Oral Dosage Forms

PYRIDOXINE HYDROCHLORIDE EXTENDED-RELEASE CAPSULES

Usual adult and adolescent dose
Deficiency (prophylaxis)—Oral, amount based on normal daily recommended intakes {29}
Adolescent and adult males—1.7 to 2 mg.

Adolescent and adult females—1.4 to 1.6 mg.

Pregnant females—2.2 mg.

Breast-feeding females—2.1 mg.

Deficiency (treatment)
Treatment dose is individualized by prescriber based on severity of deficiency.


Usual pediatric dose
Dosage form not appropriate for pediatric patients.

Strength(s) usually available
U.S.—


150 mg (OTC) [Rodex]

Canada—
Not commercially available.

Note: The strength of this pyridoxine preparation may exceed the dosage range recommended by USP DI Advisory Panels based on the amount necessary to meet normal nutritional needs.


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer. Protect from light.

Auxiliary labeling:
   • Swallow capsules whole.


PYRIDOXINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Pyridoxine Hydrochloride Extended-release Capsules.

Usual pediatric dose
Deficiency (prophylaxis)—Oral, amount based on normal daily recommended intakes {29}
Birth to 3 years of age—0.3 to 1 mg.

4 to 6 years of age—1.1 mg.

7 to 10 years of age—1.4 mg.

Deficiency (treatment)
Treatment dose is individualized by prescriber based on severity of deficiency.


Strength(s) usually available
U.S.—


10 mg (OTC)[Generic]


25 mg (OTC) [Nestrex{20}][Generic]


50 mg (OTC)[Generic]


100 mg (OTC)[Generic]


200 mg (OTC)[Generic]


250 mg (OTC)[Generic]


500 mg (OTC)[Generic]

Canada—


25 mg (OTC)[Generic]{24}


50 mg (OTC)[Generic]


100 mg (OTC)[Generic]


250 mg (OTC)[Generic]

Note: Some strengths of these pyridoxine preparations may exceed the dosage range recommended by USP DI Advisory Panels based on the amount necessary to meet normal nutritional needs.


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container. Protect from light.


PYRIDOXINE HYDROCHLORIDE EXTENDED-RELEASE TABLETS

Usual adult and adolescent dose
See Pyridoxine Hydrochloride Extended-release Capsules.

Usual pediatric dose
Dosage form not appropriate for pediatric patients.

Strength(s) usually available
U.S.—


100 mg (OTC)[Generic]{20}{23}


200 mg (OTC)[Generic]{23}


500 mg (OTC)[Generic]{23}

Canada—
Not commercially available.

Note: Some strengths of these pyridoxine preparations may exceed the dosage range recommended by USP DI Advisory Panels based on the amount necessary to meet normal nutritional needs.




Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

PYRIDOXINE HYDROCHLORIDE INJECTION USP

Usual adult and adolescent dose
Deficiency (prophylaxis)
Intravenous infusion, as part of total parenteral nutrition solutions, the specific amount determined by individual patient need.

Deficiency (treatment)
In patients receiving total parenteral nutrition: The specific amount determined by individual patient need.

Pyridoxine dependency syndrome: Initial—Intramuscular or intravenous, 30 to 600 mg per day. {01}

Drug-induced deficiency: Intramuscular or intravenous, 50 to 200 mg per day for three weeks, followed by 25 to 100 mg per day as needed. {03}

[Cycloserine poisoning]
Intramuscular or intravenous, 300 mg or more per day.

[Isoniazid poisoning (10 grams or more)]
An amount of pyridoxine equal to amount of isoniazid ingested—Intravenous, 4 grams followed by 1 gram intramuscular every 30 minutes. {01}


Usual pediatric dose
Deficiency (prophylaxis)
Intravenous infusion, as part of total parenteral nutrition solutions, the specific amount determined by individual patient need.

Deficiency (treatment)
In patients receiving total parenteral nutrition: The specific amount determined by individual patient need.

Pyridoxine dependency syndrome in infants (with seizures): Initial—Intramuscular or intravenous, 10 to 100 mg. {03}


Strength(s) usually available
U.S.—


100 mg per mL (Rx) [Beesix (1.5% benzyl alcohol){20}] [Doxine{21}] [Pyri{22}] [Rodex] [Vitabee 6][Generic]

Canada—


100 mg per mL (Rx)[Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.



Revised: 05/01/1995



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