L-Methyl Folate + Metformin + Methylcobalamin/Mecobalamin + Myo-Inositol

Usage

• This combination is primarily prescribed for the treatment of Polycystic Ovary Syndrome (PCOS) in women of reproductive age. It addresses hormonal imbalances, insulin resistance, and metabolic disturbances commonly associated with PCOS. It may also be used to improve ovulation and regulate menstrual cycles. It helps to lower high homocysteine levels, improve hormonal balance, aid follicular development, improve egg quality, and restore ovulation in women.

• Pharmacological Classification: This combination includes multiple classifications:

  • Metformin: Biguanide, Antidiabetic
  • Myo-inositol & D-Chiro-inositol: Insulin sensitizers
  • L-Methylfolate: Vitamin, Folate derivative
  • Methylcobalamin: Vitamin, Cobalamin (Vitamin B12)

• Mechanism of Action: The components work synergistically:

  • Metformin decreases hepatic glucose production, increases insulin sensitivity, and improves glucose uptake.
  • Myo-inositol & D-Chiro-inositol improve insulin signaling, especially in the ovaries, regulating ovarian function and oocyte quality.
  • L-Methylfolate reduces elevated homocysteine levels, mitigating cardiovascular risks.
  • Methylcobalamin is crucial for nerve function, DNA synthesis, and homocysteine metabolism.

Alternate Names

• Metformin + Myo-inositol + D-Chiro-inositol + L-Methylfolate + Methylcobalamin
• Brand names like Oosure-M, Met-Innovfol, and Ovalife Met.

How It Works

• Pharmacodynamics:

  • Metformin reduces hepatic gluconeogenesis and increases insulin sensitivity.
  • Inositols influence insulin signaling pathways.
  • L-methylfolate and methylcobalamin are cofactors in metabolic processes.

• Pharmacokinetics:

  • Absorption, metabolism, and elimination pathways vary for each component.
  • Metformin is partially absorbed and renally excreted.
  • Inositols are absorbed and utilized intracellularly.
  • L-methylfolate and methylcobalamin are metabolized and excreted via various pathways.

• Mode of Action:

  • Metformin’s precise mechanism is not fully understood but involves AMP-activated protein kinase (AMPK) activation.
  • Inositols act as second messengers in insulin signaling.
  • L-methylfolate is involved in one-carbon metabolism.
  • Methylcobalamin participates in DNA synthesis and methylation reactions.

• Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation:

  • Metformin may indirectly affect insulin receptor activity.
  • Inositols may influence insulin receptor substrate (IRS) proteins.
  • L-methylfolate and methylcobalamin do not directly bind to receptors but act as coenzymes.

• Elimination Pathways:

  • Metformin: Primarily renal excretion.
  • Inositols: Metabolism and excretion not fully characterized.
  • L-methylfolate and methylcobalamin: Various pathways.

Dosage

Dosage should be individualized based on patient needs and clinical response.

Standard Dosage

Adults:

• Typical dosage is one tablet containing the combined components once or twice daily with meals.
• Exact dosages of individual components vary based on the specific formulation.

Children:

• Safety and efficacy not established in children. Use is generally not recommended.

Special Cases:

• Elderly Patients: Start with a lower dose and titrate gradually, considering renal function.
• Patients with Renal Impairment: Dose reduction is necessary depending on creatinine clearance.
• Patients with Hepatic Dysfunction: Metformin is contraindicated in moderate to severe hepatic impairment. Caution is advised for other components.
• Patients with Comorbid Conditions: Careful monitoring and dose adjustments may be necessary. Monitor blood glucose levels regularly in diabetic patients.

Clinical Use Cases

This drug combination is not typically used in acute clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. It is primarily used for the chronic management of PCOS.

Dosage Adjustments

• Modifications are based on renal/hepatic function, other metabolic disorders, and patient response.
• Genetic polymorphisms affecting drug metabolism may also necessitate dose adjustments.

Side Effects

Common Side Effects:

• Nausea, vomiting, diarrhea, stomach pain, loss of appetite, changes in taste, metallic taste, headache, tiredness, skin rash, itching.

Rare but Serious Side Effects:

• Lactic acidosis (metformin), allergic reactions.

Long-Term Effects:

• Potential vitamin B12 deficiency (metformin).

Adverse Drug Reactions (ADR):

• Lactic acidosis (metformin) requires immediate medical attention.

Contraindications

• Hypersensitivity to any of the components.
• Severe renal impairment.
• Hepatic impairment (metformin contraindicated).
• Metabolic acidosis.
• Untreated vitamin B12 deficiency.
• Active malignancy (unless under close medical supervision).

Drug Interactions

• Folate antagonists (methotrexate).
• Anticonvulsants (phenytoin).
• Proton pump inhibitors and H2 blockers (omeprazole, ranitidine).
• Bile acid sequestrants (cholestyramine).
• Other antidiabetic medications.
• Nitrous oxide anesthesia.
• Alcohol.

Pregnancy and Breastfeeding

• The safety of this combination during pregnancy and breastfeeding has not been fully established. Metformin is generally considered safe during pregnancy.
• Caution advised; benefits should be weighed against potential fetal/neonatal risks. Consult a physician before use.

Drug Profile Summary

• Mechanism of Action: See “Mechanism of Action” above.
• Side Effects: Nausea, vomiting, diarrhea, stomach pain, loss of appetite, metallic taste, lactic acidosis (rare).
• Contraindications: Hypersensitivity, severe renal/hepatic impairment, metabolic acidosis.
• Drug Interactions: See “Drug Interactions” above.
• Pregnancy & Breastfeeding: Caution advised; consult a physician.
• Dosage: Individualized; typically one tablet once or twice daily with meals.
• Monitoring Parameters: Blood glucose levels (especially in diabetics), renal function, vitamin B12 levels (with long-term metformin use).

Popular Combinations

• This combination itself represents a common and popular approach to managing PCOS.

Precautions

• Pre-screening for allergies, metabolic disorders, and organ dysfunction is essential.
• Pregnant Women: Assess risks and benefits; consult a physician.
• Breastfeeding Mothers: Potential for neonatal exposure.
• Children & Elderly: Not generally recommended for children; elderly patients require careful monitoring.
• Lifestyle Considerations: Avoid excessive alcohol intake.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for L-Methyl Folate + Metformin + Methylcobalamin/Mecobalamin + Myo-Inositol?

A: The dosage should be individualized. Typically, one tablet containing the combined components is taken once or twice daily with meals. The exact dosages of the individual components can vary based on the specific formulation.

Q2: What are the common side effects?

A: Common side effects include nausea, vomiting, diarrhea, stomach pain, loss of appetite, changes in taste, and a metallic taste.

Q3: Is this combination safe during pregnancy?

A: The safety of this combination has not been definitively established. Consult with a physician before use during pregnancy or while breastfeeding.

Q4: Can this combination be used in patients with kidney disease?

A: Patients with kidney disease should exercise caution as dose adjustment may be needed. Consult a physician before use.

Q5: How does metformin work in this combination?

A: Metformin improves insulin sensitivity and decreases hepatic glucose production.

Q6: What is the role of inositols in PCOS treatment?

A: Myo-inositol and D-chiro-inositol improve insulin signaling and ovarian function, potentially improving oocyte quality.

Q7: What are the serious side effects I should be aware of?

A: While rare, lactic acidosis is a severe side effect associated with metformin and requires immediate medical attention.

Q8: Are there any drug interactions I should be aware of?

A: Yes, several drug interactions can occur. It is essential to inform your physician about all other medications you are taking, including over-the-counter drugs and supplements. Significant interactions can occur with folate antagonists, anticonvulsants, proton pump inhibitors, and other antidiabetic medications.

Q9: Can this medication affect my ability to drive?

A: It is not clear whether this combination affects driving ability. However, some side effects, such as nausea or dizziness, could impair driving. Exercise caution.

Q10: What should I do if I miss a dose?

A: If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue your regular dosing schedule. Do not double the dose.