Clomiphene + Folic Acid + Methylcobalamin

Usage

This combination is primarily prescribed off-label for male infertility, specifically in cases of low testosterone levels and impaired spermatogenesis. It addresses nutritional deficiencies that may contribute to infertility. Clomiphene is primarily indicated for female infertility due to anovulation. Folic acid and Methylcobalamin may be prescribed for other conditions not related to infertility.

Pharmacological Classification:

• Clomiphene: Selective Estrogen Receptor Modulator (SERM), Ovulation Stimulant
• Folic Acid: Vitamin, Nutritional Supplement
• Methylcobalamin: Vitamin, Nutritional Supplement

Mechanism of Action:

• Clomiphene: Blocks estrogen receptors in the hypothalamus and pituitary, decreasing negative feedback and increasing the release of gonadotropin-releasing hormone (GnRH). This leads to elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, stimulating testosterone production and spermatogenesis in males. In females, it stimulates ovulation.
• Folic Acid: Essential for DNA synthesis, cell division, and red blood cell production, crucial for overall reproductive health.
• Methylcobalamin: A coenzyme involved in various metabolic processes, including nerve function, DNA synthesis, and red blood cell formation, supporting healthy sperm production.

Alternate Names

• Clomiphene: Clomid, Serophene, Clomiphene Citrate
• Folic Acid: Vitamin B9, Folate
• Methylcobalamin: Mecobalamin, Cyanocobalamin, Vitamin B12

Brand Names: Infernia M Tablet, Clofert Max and several others.

How It Works

Pharmacodynamics:

• Clomiphene: Increases LH and FSH levels, stimulating the testes to produce testosterone and sperm in males. In females, induces ovulation.
• Folic Acid: Supports DNA synthesis, cell division, and erythropoiesis.
• Methylcobalamin: Acts as a coenzyme in various metabolic pathways.

Pharmacokinetics:

• Clomiphene: Absorbed orally, metabolized in the liver, excreted primarily in feces.
• Folic Acid: Absorbed in the small intestine, metabolized in the liver, excreted in urine.
• Methylcobalamin: Absorbed in the gastrointestinal tract, stored in the liver, excreted in urine.

Mode of Action:

• Clomiphene: Competitive antagonist at estrogen receptors in the hypothalamus and pituitary.
• Folic Acid: Converted to tetrahydrofolic acid, a coenzyme for various metabolic processes.
• Methylcobalamin: Coenzyme for methionine synthase and methylmalonyl-CoA mutase.

Elimination Pathways:

• Clomiphene: Primarily fecal excretion.
• Folic Acid: Renal excretion.
• Methylcobalamin: Renal excretion.

Dosage

The dosage information provided here pertains specifically to the combination’s use in male infertility, primarily based on common off-label practices. Dosages for female infertility differ. The use of Clomiphene in males is off-label, and dosages may vary. Always confirm dosages and treatment duration with the prescribing physician.

Standard Dosage

Adults:

• Clomiphene: 25mg daily for 25 days each month or 25mg every other day.
• Folic Acid: 5mg to 15mg orally per day.
• Methylcobalamin: 1500mcg per day.

Children:

This combination is not typically used in children for infertility.

Special Cases:

• Elderly Patients: Dosage adjustments may be necessary based on individual patient needs and organ function.
• Patients with Renal Impairment: Dose modification may be required.
• Patients with Hepatic Dysfunction: Dose adjustment may be required.
• Patients with Comorbid Conditions: Individualized dosing based on specific conditions.

Clinical Use Cases

The provided combination is not typically used in the listed clinical settings. Clomiphene is used for ovulation induction.

Dosage Adjustments

Dose modifications should be considered based on renal/hepatic function, other medical conditions, and patient response.

Side Effects

Common Side Effects

• Clomiphene: Hot flashes, headache, blurred vision, nausea, abdominal discomfort.
• Folic Acid: Generally well-tolerated, rarely nausea, bloating, loss of appetite.
• Methylcobalamin: Generally well-tolerated.

Rare but Serious Side Effects

• Clomiphene: Ovarian hyperstimulation syndrome (OHSS), visual disturbances, multiple pregnancies.

Long-Term Effects

• Clomiphene: Potential for vision changes with prolonged use.

Adverse Drug Reactions (ADR)

• Clomiphene: OHSS requiring urgent medical attention, severe allergic reactions.

Contraindications

• Clomiphene: Pregnancy, liver disease, abnormal uterine bleeding, ovarian cysts (not due to PCOS), pituitary tumor, uncontrolled thyroid or adrenal dysfunction.
• Folic Acid: Rare hypersensitivity.
• Methylcobalamin: Hypersensitivity to Vitamin B12 or Cobalt.

Drug Interactions

• Clomiphene: Limited known drug interactions. Consult a drug interaction database for details.
• Folic Acid: May interact with certain anticonvulsants (e.g., phenytoin).
• Methylcobalamin: May interact with certain medications affecting vitamin B12 absorption.
• Alcohol: May reduce the absorption of folic acid.

Pregnancy and Breastfeeding

Clomiphene is contraindicated in pregnancy. Folic acid is generally recommended during pregnancy. Consult specialist resources for information regarding methylcobalamin use during pregnancy and for all three medications during breastfeeding. This combination is typically prescribed for male infertility and is not relevant during pregnancy and breastfeeding when given to the male partner.

Drug Profile Summary (See previous sections for detailed information)

Popular Combinations

This specific combination is not a standard or widely used combination. It is crucial to consult specialist resources for evidence-based information.

Precautions (See previous sections for detailed information)

FAQs (Frequently Asked Questions)

(Refer to the information provided in the previous sections for the answers to some of these questions.)

Q1: What is the recommended dosage for Clomiphene + Folic Acid + Methylcobalamin for male infertility? A: Clomiphene 25mg daily for 25 days per month, Folic Acid 5-15 mg daily, Methylcobalamin 1500mcg daily. Dosing is off-label and should be confirmed with a specialist.

Q2: What are the primary uses of this combination? A: Primarily used off-label for male infertility, particularly with low testosterone and impaired spermatogenesis.

Q3: What are the common side effects of clomiphene? A: Hot flashes, headache, blurred vision, nausea, and abdominal discomfort.

Q4: Are there any serious side effects I should be aware of? A: Yes, though rare, clomiphene can cause Ovarian Hyperstimulation Syndrome (OHSS) and visual disturbances. Immediate medical attention is needed if these occur.

Q5: Can this combination be used in women trying to conceive? A: Clomiphene is used in women for ovulation induction, but this combination is not standard practice. The specific combination is primarily used off-label in male infertility. If the woman is pregnant or trying to conceive, Clomiphene is contraindicated.

Q6: How does clomiphene affect hormone levels? A: Clomiphene blocks estrogen receptors, leading to increased GnRH, LH, and FSH, which stimulate testosterone production and spermatogenesis in males. In females, this hormonal cascade leads to ovulation.

Q7: What are the contraindications for clomiphene? A: Pregnancy, liver disease, abnormal uterine bleeding, ovarian cysts not due to PCOS, pituitary tumors, and uncontrolled thyroid or adrenal dysfunction.

Q8: Are there any drug interactions I should be aware of? A: Consult a drug interaction database for detailed information. Folic acid may interact with some anticonvulsants. Methylcobalamin may interact with medications affecting B12 absorption. Alcohol can reduce folic acid absorption.

Q9: What monitoring is necessary while a patient is on clomiphene therapy? A: Regular semen analysis and monitoring for side effects, especially vision changes and signs of OHSS. Hormone levels (LH, FSH, testosterone) should also be checked regularly.