Folic Acid + Methylcobalamin + Pregabalin + Vitamin B6

Usage

This combination is primarily prescribed for the management of neuropathic pain, particularly in conditions like diabetic neuropathy, post-herpetic neuralgia, fibromyalgia, and peripheral neuropathy. It is also used as adjunctive therapy for adult patients with partial onset seizures.

Its pharmacological classifications include:

• Pregabalin: Anticonvulsant, analgesic, anxiolytic
• Methylcobalamin: Vitamin, nutritional supplement
• Folic Acid: Vitamin, nutritional supplement
• Vitamin B6 (Pyridoxine): Vitamin, nutritional supplement

This combination works by addressing multiple aspects of neuropathic pain. Pregabalin reduces pain signals by modulating calcium channels on nerve cells, thus decreasing the release of neurotransmitters associated with pain. Methylcobalamin and Vitamin B6 support nerve regeneration and myelin production, while Folic acid helps maintain nerve health and function.

Alternate Names

This combination does not have a universally recognized International Nonproprietary Name (INN). It is often referred to based on its components. Some common alternate names include Pregabalin + Methylcobalamin + Folic acid + Vitamin B6 combination or Pregabalin/Mecobalamin/Folic acid/Pyridoxine. It may also be referenced by brand names, some examples include: Pregator, Abetaneuron PG, Alnacob Forte (note that formulations may include additional ingredients, e.g. alpha lipoic acid or benfotiamine).

How It Works

Pharmacodynamics: Pregabalin binds to the alpha-2-delta subunit of voltage-gated calcium channels, reducing calcium influx into nerve terminals and decreasing the release of excitatory neurotransmitters like glutamate, noradrenaline, and substance P. Methylcobalamin is a cofactor for methionine synthase, crucial for myelin synthesis and nerve regeneration. Vitamin B6 is involved in the synthesis of neurotransmitters like serotonin and GABA, contributing to neuroprotection. Folic acid is involved in DNA synthesis and repair, essential for nerve cell function.

Pharmacokinetics:

• Pregabalin: Rapidly absorbed orally, reaching peak plasma concentrations within 1 hour. It is primarily excreted unchanged in the urine. The half-life is approximately 6 hours.
• Methylcobalamin: Absorbed in the gastrointestinal tract, metabolized in the liver, and excreted in urine and bile.
• Folic Acid: Absorbed in the small intestine, metabolized in the liver, and excreted in the urine.
• Vitamin B6: Readily absorbed in the gastrointestinal tract, metabolized in the liver to 4-pyridoxic acid, and excreted in urine.

Mode of Action: Pregabalin’s mode of action is primarily through its interaction with voltage-gated calcium channels, specifically the alpha-2-delta subunit. This interaction reduces calcium influx into nerve terminals, which in turn decreases the release of neurotransmitters associated with pain signaling. The B vitamins work by supporting various metabolic processes related to nerve function, including myelin synthesis and neurotransmitter production.

Elimination pathways: Pregabalin is eliminated primarily through renal excretion, with minimal hepatic metabolism. Methylcobalamin is excreted in both urine and bile, reflecting both renal and hepatic elimination. Folic acid and vitamin B6 are primarily excreted in urine after hepatic metabolism.

Dosage

Dosage should be individualized based on patient response and tolerability.

Standard Dosage

Adults:

Pregabalin dosing usually begins at 75mg twice daily or 50mg three times daily. The dose can be increased to a maximum of 600mg/day based on efficacy and tolerability. Methylcobalamin, folic acid, and vitamin B6 dosages vary depending on the specific formulation and clinical context.

Children:

The safety and efficacy of this combination in children under 18 have not been established, and its use is generally not recommended. Some formulations may be approved for adolescents, in which case specific pediatric dosing guidelines should be followed.

Special Cases:

• Elderly Patients: Dosage adjustments may be necessary due to age-related decline in renal function. Start with a lower dose and titrate cautiously.

• Patients with Renal Impairment: Dose reduction is required for patients with renal impairment based on creatinine clearance. Consult specific guidelines for pregabalin dosing adjustments.

• Patients with Hepatic Dysfunction: No dosage adjustment is typically required for pregabalin. The metabolism of other components may be affected, but dose adjustments are usually not necessary.

• Patients with Comorbid Conditions: Use with caution in patients with congestive heart failure, peripheral edema, or other conditions that may be exacerbated by fluid retention, as this combination can cause edema in some individuals.

Clinical Use Cases

The use of this specific combination in settings such as intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations isn’t standard practice. Pregabalin may be used in certain pain management protocols, but its role is typically distinct from these acute care scenarios.

Dosage Adjustments

Adjustments are necessary based on renal function, patient response, and tolerability.

Side Effects

Common Side Effects

Dizziness, drowsiness, fatigue, nausea, dry mouth, peripheral edema, weight gain, blurred vision, ataxia.

Rare but Serious Side Effects

Angioedema, hypersensitivity reactions, suicidal ideation, rhabdomyolysis, Stevens-Johnson syndrome, anaphylaxis.

Long-Term Effects

Weight gain, cognitive impairment, dependency.

Adverse Drug Reactions (ADR)

Severe allergic reactions, including anaphylaxis, severe skin reactions (e.g. Stevens-Johnson Syndrome), suicidal ideation and behavior.

Contraindications

Hypersensitivity to any component of the formulation, angioedema history related to pregabalin use.

Drug Interactions

• CNS Depressants: Alcohol, opioids, benzodiazepines, and other CNS depressants can potentiate drowsiness and dizziness.
• Antidiabetic Medications: May alter blood glucose control; monitor closely.
• Lorazepam, Oxycodone: Concurrent use may enhance CNS depressive effects.
• Angiotensin-Converting Enzyme (ACE) Inhibitors: May increase the risk of angioedema.

Pregnancy and Breastfeeding

Pregabalin is Pregnancy Category C. There are limited data on the use of this combination during pregnancy and breastfeeding. Use only if the potential benefit outweighs the potential risk to the fetus or nursing infant. Consider safer alternatives when available.

Drug Profile Summary

• Mechanism of Action: See “How It Works” above.
• Side Effects: Dizziness, drowsiness, fatigue, nausea, weight gain, edema, blurred vision. Serious but rare: angioedema, suicidal ideation, hypersensitivity reactions.
• Contraindications: Hypersensitivity, angioedema history with pregabalin.
• Drug Interactions: CNS depressants, antidiabetics, lorazepam, oxycodone, ACE inhibitors.
• Pregnancy & Breastfeeding: Use with caution; Category C.
• Dosage: See “Dosage” above.
• Monitoring Parameters: Renal function, blood glucose (in diabetics), mood changes, adverse effects.

Popular Combinations

This combination itself is a popular combination for neuropathic pain. There might be other combinations used with it based on specific patient needs like analgesics or other drugs to manage comorbid conditions.

Precautions

Assess renal function and adjust dosage as needed. Monitor for mood changes and suicidal thoughts. Caution patients about potential for dizziness and drowsiness. Advise against alcohol consumption.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Folic Acid + Methylcobalamin + Pregabalin + Vitamin B6?

A: Pregabalin dosing typically starts at 75mg BID or 50mg TID, titratable up to 600 mg/day. Dosages for other components vary by formulation. Dosage adjustment is necessary for renal impairment.

Q2: What are the common side effects?

A: Dizziness, drowsiness, fatigue, nausea, dry mouth, weight gain, and edema.

Q3: Can this combination be used during pregnancy?

A: Pregabalin is Pregnancy Category C. It should be used only if the potential benefit outweighs the risk.

Q4: What are the drug interactions to be aware of?

A: CNS depressants, antidiabetics, lorazepam, oxycodone, and ACE inhibitors.

Q5: How does pregabalin work in this combination?

A: It binds to the alpha-2-delta subunit of voltage-gated calcium channels, reducing pain signal transmission.

Q6: How do the B vitamins contribute to the effectiveness of this combination?

A: They support nerve health, myelin production, and neurotransmitter synthesis.

Q7: What precautions are necessary when prescribing this combination?

A: Monitor renal function, blood glucose, and for mood changes/suicidal ideation. Advise patients about dizziness and drowsiness and recommend avoiding alcohol.

Q8: Are there any contraindications to using this combination?

A: Hypersensitivity to any component and history of angioedema related to pregabalin use.

Q9: How long does it take to see the full benefits of this combination?

A: Initial pain relief may occur within 2 weeks, but full benefits can take 2-3 months.

Q10: What should a patient do if they miss a dose?

A: Take the missed dose as soon as remembered unless it is close to the next scheduled dose. Do not double the dose.