Usage
Clomiphene + Melatonin is prescribed for the treatment of female infertility, specifically in women who are not ovulating regularly or who have ovulatory disorders like polycystic ovary syndrome (PCOS). It is a combination of two drugs: Clomiphene, an ovarian stimulant, and Melatonin, a nutraceutical/hormone. The combination aims to induce ovulation and potentially improve egg quality.
Alternate Names
This combination is not widely recognized by a single international nonproprietary name (INN). It’s often referred to by its component drugs (Clomiphene Citrate + Melatonin) or marketed under various brand names such as Clomipure, Qucophene-M, Ovanit-M and Orinest M100.
How It Works
Pharmacodynamics: Clomiphene is a selective estrogen receptor modulator (SERM). It binds to estrogen receptors in the hypothalamus, disrupting the normal estrogen feedback loop. This leads to increased secretion of gonadotropin-releasing hormone (GnRH), which in turn stimulates the pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The elevated FSH and LH levels promote follicular growth and ovulation. Melatonin acts as an antioxidant, scavenging free radicals and protecting the ovaries from oxidative stress, potentially improving egg quality. It also plays a role in regulating reproductive hormones.
Pharmacokinetics: Clomiphene is well-absorbed orally and is metabolized in the liver by CYP enzymes. It is primarily excreted in the feces. Melatonin is also well-absorbed orally and is metabolized in the liver, mainly by CYP1A2, to 6-sulfatoxymelatonin. It’s excreted primarily in urine.
Mode of action: Clomiphene acts by competitive antagonism at estrogen receptors in the hypothalamus and pituitary gland. Melatonin’s antioxidant properties protect the ovaries from damage by free radicals. It also influences the hypothalamic-pituitary-gonadal axis, but the precise mechanism is not fully elucidated.
Dosage
Dosage information for this combination is not consistently standardized and varies by brand and clinical practice. Always follow the prescribing physician’s instructions.
Standard Dosage
Adults:
Specific dosing regimens are determined by the physician based on the individual patient’s condition and response. Typically, Clomiphene is started at 50 mg daily for 5 days, usually starting on day 2-5 of the menstrual cycle. This can be increased to 100 mg daily if ovulation does not occur. Melatonin dosage may vary from 2mg to 5mg taken shortly before bedtime.
Children:
This combination is not indicated for use in children.
Special Cases:
- Elderly Patients: Not typically used in postmenopausal women.
- Patients with Renal Impairment: Dosage adjustments may be necessary. Consult with a nephrologist.
- Patients with Hepatic Dysfunction: Dosage adjustments may be necessary. Consult with a hepatologist.
- Patients with Comorbid Conditions: Use with caution in patients with liver disease, abnormal uterine bleeding, uterine fibroids, ovarian cysts, endometriosis, thyroid or adrenal gland problems, hypertriglyceridemia, diabetes, epilepsy, or autoimmune diseases.
Clinical Use Cases
Clomiphene + Melatonin combination is specifically used for ovulation induction in infertility. It’s not indicated for use in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose modifications should be based on individual patient response and tolerance. Consider renal and hepatic function, other medical conditions, and concomitant medications.
Side Effects
Common Side Effects:
- Hot flashes
- Abdominal or pelvic discomfort (bloating, pain)
- Headache
- Nausea and vomiting
- Breast discomfort
- Intermenstrual bleeding
Rare but Serious Side Effects:
- Ovarian hyperstimulation syndrome (OHSS)
- Visual disturbances (blurred vision, spots, flashes)
- Multiple pregnancies
Long-Term Effects:
- Potential risk of ovarian tumors with prolonged use (more than 6 cycles)
Contraindications
- Pregnancy
- Breastfeeding
- Unexplained abnormal vaginal bleeding
- Ovarian cysts (unrelated to PCOS)
- Liver disease
- Pituitary or other brain tumors
- Uncontrolled thyroid or adrenal gland dysfunction
- Hypersensitivity to clomiphene or melatonin
Drug Interactions
- Clomiphene can interact with other drugs that affect estrogen levels, such as tamoxifen, letrozole, and oral contraceptives.
- Melatonin may interact with certain medications, including fluvoxamine, CYP1A2 inhibitors/inducers, CNS depressants, and anticoagulants.
- Alcohol, smoking, and grapefruit juice may also influence drug metabolism and effects. Consult a physician for personalized guidance.
Pregnancy and Breastfeeding
Clomiphene + Melatonin is contraindicated in pregnancy and breastfeeding. It should be discontinued if pregnancy is suspected.
Drug Profile Summary
- Mechanism of Action: Clomiphene: SERM, stimulates ovulation; Melatonin: Antioxidant, regulates sleep-wake cycle.
- Side Effects: Hot flashes, abdominal/pelvic discomfort, headache, nausea/vomiting, ovarian enlargement, visual disturbances.
- Contraindications: Pregnancy, breastfeeding, liver disease, ovarian cysts, unexplained vaginal bleeding, pituitary tumors.
- Drug Interactions: Consult a physician for personalized guidance based on individual patient medications and condition.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: As directed by the physician.
- Monitoring Parameters: Ovarian response via ultrasound, hormone levels (FSH, LH, estradiol).
Popular Combinations
While Clomiphene is sometimes used in combination with other fertility medications, the specific combination of Clomiphene + Melatonin as a fixed-dose combination is not itself widely established as a standard therapy. Therefore, recommendations for “popular combinations” are not applicable in this context.
Precautions
- Pre-existing medical conditions should be thoroughly evaluated before initiating treatment.
- Monitor for signs of ovarian hyperstimulation syndrome.
- Patients should be counseled on the risk of multiple pregnancies.
- Exercise caution when driving or operating machinery due to potential visual side effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Clomiphene + Melatonin?
A: Dosage is individualized based on the patient’s specific condition and response. A common starting dose is Clomiphene 50mg daily for 5 days, beginning on day 2-5 of the cycle. Melatonin dosages may range from 2mg to 5mg before bed.
Q2: How does this combination improve fertility?
A: Clomiphene stimulates ovulation, while Melatonin potentially improves egg quality and the uterine lining receptiveness.
Q3: What are the most common side effects?
A: Hot flashes, abdominal or pelvic discomfort, headaches, and nausea are common side effects.
Q4: Can this combination be used in women with PCOS?
A: Yes, it is often used in women with PCOS to induce ovulation, but with careful monitoring due to the risk of OHSS.
Q5: Are there any long-term risks associated with Clomiphene + Melatonin?
A: Prolonged use (more than 6 cycles) of Clomiphene may increase the risk of ovarian tumors.
Q6: Can I take this medication if I am breastfeeding?
A: No, this medication is contraindicated during breastfeeding.
Q7: What should I do if I miss a dose?
A: Contact your physician for guidance.
Q8: What are the signs of ovarian hyperstimulation syndrome (OHSS)?
A: Symptoms can include severe pelvic pain, bloating, nausea, vomiting, rapid weight gain, and difficulty breathing. Seek immediate medical attention if these occur.
Q9: How long should I take Clomiphene + Melatonin before seeing a fertility specialist?
A: If pregnancy does not occur after 3-6 cycles of Clomiphene, further evaluation by a fertility specialist is recommended.
Q10: What lifestyle modifications can support fertility treatment?
A: Maintaining a healthy weight, following a balanced diet, managing stress, and avoiding smoking and excessive alcohol consumption can positively influence fertility outcomes.
