Pyridoxine Hydrochloride

Usage

Pyridoxine Hydrochloride, also known as Vitamin B6, is prescribed for various medical conditions, including:

• Pyridoxine deficiency: Treatment and prevention of deficiency resulting from inadequate dietary intake, malabsorption, or certain medications (e.g., isoniazid).
• Sideroblastic anemia: A type of anemia where the bone marrow produces ringed sideroblasts rather than healthy red blood cells. Pyridoxine is often effective in treating this specific anemia.
• Pyridoxine-dependent seizures: A rare genetic disorder causing seizures in infants.
• Nausea and vomiting of pregnancy: Often used in combination with doxylamine.
• Peripheral neuropathy caused by isoniazid therapy for tuberculosis.

Pharmacological Classification: Vitamin, water-soluble B-complex vitamin. It can also be classified based on its use as an anticonvulsant (in specific cases like pyridoxine-dependent seizures), antiemetic (for nausea and vomiting in pregnancy), or a hematinic agent (in sideroblastic anemia).

Mechanism of Action: Pyridoxine is a precursor to pyridoxal 5’-phosphate (PLP), the active form of vitamin B6. PLP is a crucial cofactor for numerous enzymes involved in amino acid metabolism, neurotransmitter synthesis (including serotonin, dopamine, GABA), heme synthesis, and glycogenolysis.

Alternate Names

• Vitamin B6
• Pyridoxal
• Pyridoxamine
• Adermine

Brand Names:

• Nestrex

How It Works

Pharmacodynamics: Pyridoxine exerts its effects through PLP, which acts as a coenzyme in numerous metabolic reactions. It plays a vital role in:

• Amino acid metabolism: Transamination, decarboxylation, deamination, and synthesis of non-essential amino acids.
• Neurotransmitter synthesis: Synthesis of serotonin, dopamine, GABA, norepinephrine, and histamine.
• Heme synthesis: A crucial component of hemoglobin, myoglobin, and cytochromes.
• Glycogenolysis: Breakdown of glycogen into glucose.

Pharmacokinetics:

• Absorption: Readily absorbed from the GI tract following oral administration. IM/IV routes are also available.
• Metabolism: Converted to the active form, PLP, primarily in the liver.
• Elimination: Primarily renal excretion, with a small amount excreted in bile.

Mode of Action: PLP acts as a coenzyme by binding to and activating various enzymes. Its mechanism involves Schiff base formation with amino acids, facilitating various reactions.

Receptor binding, enzyme inhibition, or neurotransmitter modulation: Primarily acts as an enzyme cofactor rather than a direct receptor agonist/antagonist or enzyme inhibitor. However, it modulates neurotransmitter levels by acting as a cofactor in their synthesis.

Elimination Pathways: Primarily renal excretion, with a small amount excreted in bile.

Dosage

Standard Dosage

Adults:

• Dietary supplement: 1.3-1.7 mg/day (RDA).
• Deficiency: 2.5-10 mg/day orally, or 10-100 mg IV/IM for 3 weeks followed by 2.5-10 mg/day orally.
• Nausea and vomiting of pregnancy: 10-25 mg every 8 hours, not exceeding 75 mg/day.
• Isoniazid-induced neuropathy prevention: 25-50 mg/day.

Children:

• Dietary supplement: 0.1-1.3 mg/day depending on age.
• Deficiency: Dose adjusted based on age and severity of deficiency.
• Pyridoxine-dependent seizures: 10-100 mg IV/IM.

Special Cases:

• Elderly Patients: Standard adult dosage, monitor for potential adverse effects.
• Patients with Renal Impairment: Dose adjustment based on creatinine clearance may be necessary in severe renal dysfunction.
• Patients with Hepatic Dysfunction: Generally no dose adjustment required but close monitoring recommended.
• Patients with Comorbid Conditions: Adjust dose based on specific conditions and other medications.

Clinical Use Cases

Dosage adjustments are usually based on clinical response and patient-specific factors. Specific clinical guidelines should be consulted for these contexts:

• Intubation: Not routinely administered.
• Surgical Procedures: Not routinely administered.
• Mechanical Ventilation: Not routinely administered.
• Intensive Care Unit (ICU) Use: May be used in cases of documented deficiency.
• Emergency Situations: High-dose IV pyridoxine for pyridoxine-dependent seizures.

Dosage Adjustments

Adjustments may be needed based on renal or hepatic impairment, concomitant medications, and individual response. Always consider patient-specific factors.

Side Effects

Common Side Effects

• Nausea
• Headache
• Drowsiness
• Mild numbness/tingling in extremities

Rare but Serious Side Effects

• Sensory neuropathy (with prolonged high doses)
• Severe allergic reactions (rare)

Long-Term Effects

• Sensory neuropathy with prolonged high doses (greater than 200 mg/day)

Adverse Drug Reactions (ADR)

• Severe allergic reactions requiring immediate medical attention.

Contraindications

• Hypersensitivity to pyridoxine hydrochloride.

Drug Interactions

• Levodopa: Pyridoxine antagonizes the effects of levodopa unless it is given with carbidopa.
• Anticonvulsants (phenobarbital, phenytoin): Pyridoxine may reduce their effectiveness.
• Isoniazid, cycloserine, pyrazinamide, penicillamine: May increase the need for pyridoxine.
• Oral contraceptives: May increase the requirement for pyridoxine.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: A. Generally considered safe for use during pregnancy. Recommended daily intake during pregnancy and lactation is 2mg/day.
• Fetal Risks: No significant evidence of fetal harm with appropriate dosages.
• Breastfeeding: Pyridoxine is excreted in breast milk. Supplementation increases milk levels. No adverse effects have been reported with standard dosages.

Drug Profile Summary

• Mechanism of Action: Coenzyme in various metabolic pathways, crucial for neurotransmitter and heme synthesis.
• Side Effects: Nausea, headache, drowsiness, mild tingling/numbness (common); sensory neuropathy with high doses.
• Contraindications: Hypersensitivity.
• Drug Interactions: Levodopa, anticonvulsants, isoniazid.
• Pregnancy & Breastfeeding: Generally safe during pregnancy and breastfeeding.
• Dosage: Refer to detailed dosage guidelines above.
• Monitoring Parameters: Monitor for signs of neuropathy with high-dose therapy.

Popular Combinations

• Doxylamine succinate + pyridoxine hydrochloride for nausea and vomiting of pregnancy.

Precautions

• General Precautions: Assess for any pre-existing hypersensitivity to pyridoxine.
• Specific Populations: Consider age-specific dosing guidelines for children and the elderly. Monitor renal function for dose adjustments when necessary.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Pyridoxine Hydrochloride?

A: See detailed dosage guidelines above for adults, children, and specific conditions.

Q2: How is Pyridoxine Hydrochloride metabolized?

A: It is primarily metabolized in the liver to its active form, pyridoxal 5’-phosphate (PLP).

Q3: What are the most common side effects of Pyridoxine Hydrochloride?

A: Nausea, headache, drowsiness, and mild tingling/numbness in extremities.

Q4: Can Pyridoxine Hydrochloride be used during pregnancy?

A: Yes, it’s generally considered safe during pregnancy and is often used to treat nausea and vomiting.

Q5: What is the maximum safe dose of Pyridoxine Hydrochloride?

A: For long-term use, doses above 200mg/day are generally associated with an increased risk of neuropathy. Consult specific clinical guidelines for appropriate upper limits.

Q6: Does Pyridoxine Hydrochloride interact with any medications?

A: Yes, it can interact with levodopa, certain anticonvulsants (phenobarbital, phenytoin), isoniazid, and oral contraceptives.

Q7: How should I manage a patient experiencing sensory neuropathy from high-dose Pyridoxine?

A: Discontinue Pyridoxine and consider supportive measures. The neuropathy may be irreversible.

Q8: What is the role of Pyridoxine Hydrochloride in heme synthesis?

A: PLP, the active form of pyridoxine, is a cofactor for aminolevulinate synthase, a key enzyme in the heme biosynthesis pathway.

Q9: Can Pyridoxine Hydrochloride be used in patients with renal impairment?

A: Yes, but dosage adjustment may be necessary depending on the degree of impairment.