Pyridoxine HCl Injection

Overview of Pyridoxine HCl (Vitamin B6) Injection

Dosage Strength of Pyridoxine HCl Injection

100 mg/mL 30 mL Vial (Preserved with Benzyl Alcohol. Chlorobutanol-Free)

General Information

Pyridoxine, or vitamin B6, is a naturally occurring, water-soluble vitamin found in food such as cereal grains, legumes, vegetables, liver, meat, and eggs. Pyridoxine is used to treat and prevent vitamin B6 deficiency; to prevent or treat toxicity from isoniazid, cycloserine, or hydralazine; and to treat sideroblastic anemia associated with elevated serum iron levels. It also has been used in pyridoxine-dependent neonates to treat seizures that are unresponsive to conventional therapy and in patients with metabolic disorders such as xanthurenic aciduria, primary hyperoxaluria, primary cystathioninuria, and primary homocystinuria. Pyridoxine hydrochloride has been commercially available since approval by the FDA in 1940.

Mechanism of Action: Vitamin B6 is composed of pyridoxine, pyridoxal, and pyridoxamine, and food usually contains all three forms. Pyridoxine is converted in erythrocytes to its active moiety, pyridoxal phosphate (requiring riboflavin for the conversion), while pyridoxamine is converted into pyridoxamine phosphate. These active forms act as coenzymes for no fewer than 60 metabolic processes including the metabolism of fat, protein, and carbohydrate. Their role in protein metabolism includes decarboxylation of amino acids, conversion of tryptophan to niacin or serotonin, deamination, and transamination of amino acids. In carbohydrate metabolism, it is necessary for the conversion of glycogen to glucose-1-phosphate. Pyridoxine is essential for synthesis of gamma aminobutyric acid (GABA) in the CNS and synthesis of heme.

Pharmacokinetics

Pyridoxine is administered orally and by intramuscular or intravenous injection. Vitamin B6 is stored in the liver, with small amounts in the brain and muscles. The total body storage for adults is between 16—27 mg. Pyridoxal crosses the placenta, with fetal concentrations five times that of maternal plasma concentrations. Pyridoxal and pyridoxal phosphate are the primary forms of vitamin B6 in the blood. Pyridoxal phosphate is 100% protein-bound. The half-life of pyridoxine is 15—20 days. Conversion of pyridoxine to pyridoxal phosphate, and pyridoxamine to pyridoxamine phosphate takes place in erythrocytes. Pyridoxine is also phosphorylated in the liver. Pyridoxal is oxidized in the liver to produce 4-pyridoxic acid, which is excreted in the urine.

Indications

For nutritional supplementation in patients receiving total parenteral nutrition (TPN):

Intravenous dosage: Adults: Specific recommendations are not available; however, 10 mL/day of the IV adult parenteral multivitamin preparation, which contains 6 mg of pyridoxine, is recommended to be added to the TPN for nutritional supplementation in patients weighing more than 40 kg.1

Children and Adolescents weighing more than 40 kg: Specific recommendations are not available; however, 10 mL/day of the IV adult parenteral multivitamin preparation, which contains 6 mg of pyridoxine, is recommended to be added to the TPN for nutritional supplementation in patients weighing more than 40 kg.12

Neonates, Infants, Children, and Adolescents weighing 2.5 to 40 kg: 1 mg/day IV admixed with TPN.2

Neonates less than 2.5 kg: 0.4 mg/kg/day IV admixed with TPN. Max: 1 mg/day.2

Patients with Hepatic Impairment Dosing: Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing: Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed with oral therapy. However, limit intravenous pyridoxine use as aluminum accumulation may result (see Contraindications).

Administration Information:

Injectable Administration: Pyridoxine is administered intramuscularly or intravenously. Parenteral therapy is usually reserved for patients for which oral pyridoxine is not feasible. Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The parenteral solution should be protected from light to prevent decomposition.

Intravenous Administration: Administer as a direct IV injection or as an intermittent IV infusion in a standard IV solution. May also be admixed in compatible total parenteral nutrition (TPN) solutions.

Intramuscular Administration: Inject into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel. Rotate sites of injection.

Contraindications/Precautions

Parenteral pyridoxine solutions contain varying concentrations of aluminum. Patients with renal impairment, especially as seen in premature neonates, are at risk of aluminum accumulation which may result in toxicity. Limit intravenous pyridoxine therapy and consider the cumulative aluminum content among all therapies under administration in patients with renal impairment. It is noted that 4—5 mcg/kg/day of IV aluminum leads to accumulation at concentrations associated with CNS and bone toxicity; further, aluminum tissue loading is possible at lesser, but undefined, daily administration rates.3 Aluminum concentration in parenteral solutions can be obtained by direct manufacturer inquiry.

Appropriate maternal pyridoxine (vitamin B6) intake is encouraged during pregnancy (FDA pregnancy risk category A), and the requirement for pyridoxine appears to be increased during pregnancy.3 Pyridoxine (up to 40 mg/day) in combination with doxylamine is FDA-approved for the treatment of pregnancy-induced nausea and vomiting. No increased risk for malformations from first trimester exposures to doxylamine succinate and pyridoxine hydrochloride with or without dicyclomine hydrochloride was noted in a meta-analysis. Further, no statistically significant relationships between fetal abnormalities and the first trimester use of the combination doxylamine succinate and pyridoxine hydrochloride with or without dicyclomine hydrochloride were noted in a separate meta-analysis.4

Pyridoxine is excreted in human milk. Appropriate maternal intake of pyridoxine (vitamin B6) is important during lactation, and no problems have been identified with maternal supplementation to achieve adequate intake goals during breast-feeding. The American Academy of Pediatrics (AAP) has considered the use of pyridoxine compatible with breast-feeding.5 Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Pregnancy

Appropriate maternal pyridoxine (vitamin B6) intake is encouraged during pregnancy (FDA pregnancy risk category A), and the requirement for pyridoxine appears to be increased during pregnancy.3 Pyridoxine (up to 40 mg/day) in combination with doxylamine is FDA-approved for the treatment of pregnancy-induced nausea and vomiting. No increased risk for malformations from first trimester exposures to doxylamine succinate and pyridoxine hydrochloride with or without dicyclomine hydrochloride was noted in a meta-analysis. Further, no statistically significant relationships between fetal abnormalities and the first trimester use of the combination doxylamine succinate and pyridoxine hydrochloride with or without dicyclomine hydrochloride were noted in a separate meta-analysis.4

Breast-Feeding

Pyridoxine is excreted in human milk. Appropriate maternal intake of pyridoxine (vitamin B6) is important during lactation, and no problems have been identified with maternal supplementation to achieve adequate intake goals during breast-feeding. The American Academy of Pediatrics (AAP) has considered the use of pyridoxine compatible with breast-feeding.5 Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Adverse Reactions/Side Effects

Pyridoxine is considered nontoxic in regular doses; however, nausea/vomiting, headache, paresthesias, hyperesthesia, somnolence, and low serum folic acid levels have been reported. Excessive, chronic dosages of pyridoxine (2—6 grams/day) have been associated with a severe sensory peripheral neuropathy or neuronopathy syndrome. This may result from neuron susceptibility in the dorsal root ganglia. One patient who consumed 5 g/day developed pseudoathetosis of the outstretched arms, ataxia, and absent limb reflexes. Seven months after discontinuation of high-dose pyridoxine, she felt much improved, could walk steadily without a cane, could stand with her eyes closed, but still had shooting pains in her calves and shins. Other patients who took several g/day for several months developed unstable gait, perioral numbness, and a "stocking-glove" sensory loss. Seizures have occurred following large IV doses of pyridoxine. Seizures in neonates have occurred following the use of large doses of pyridoxine during pregnancy. Adverse neurologic reactions with lower dosages have been reported less frequently.6378

A transient worsening of metabolic acidosis, which is frequently present in patients with seizures, may occur after rapid infusion of large pyridoxine doses. Pyridoxine injection is acidic (pH 2—3.8). In a randomized, controlled crossover trial of 5 adult patients, 5000 mg of pyridoxine administered over 5 minutes induced a significant but transient increase in the base deficit; mean maximal increase in base deficit was 2.74 mEq/L at 3 minutes after infusion. Resolution occurred 30 minutes after the infusion.3 [53489]

Storage

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

  • 1. a. b. Mirtallo J, Canada T, Johnson D, et al. Safe practices for parenteral nutrition. J Parenter Enteral Nutr 2004;28(6):S39-S70.
  • 2. a. b. c. Kleinman RE. Parenteral Nutrition. In: Pediatric Nutrition Handbook. 6th ed. Elk Grove Village, Il: American Academy of Pediatrics;2009:519-540.
  • 3. a. b. c. d. e. Pyridoxine hydrochloride injection, USP package insert. Schaumburg, IL: American Pharmaceutical Partners; 2008 April.
  • 4. a. b. Diclegis (doxylamine; pyridoxine) package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2013 Apr.
  • 5. a. b. American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89.
  • 6. Schaumburg H, Kaplan J, Windebank A, et al. Sensory neuropathy from pyridoxine abuse. N Engl J Med 1983;309:445-8.
  • 7. Parry GJ, Breesen DE. Sensory neuropathy with low-dose pyridoxine. Neurology 1985;35:1466-1468.
  • 8. Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. Eur J Emerg Med 2005;12:78-85.

Related Medications