A fixed-dose combination of a selective estrogen receptor modulator (SERM) and a pineal gland hormone. Clomiphene citrate is a non-steroidal agent that stimulates ovulation by blocking estrogen receptors at the hypothalamus and pituitary, increasing gonadotropin secretion. Melatonin is a chronobiotic agent that regulates the sleep-wake cycle and has antioxidant properties. In the context of female infertility, this combination is theorized to potentially improve ovulation induction outcomes by modulating circadian rhythms and reducing oxidative stress, though robust clinical evidence for the combination is limited and it is not a standard first-line therapy.
Adult: One tablet (Clomiphene 50mg + Melatonin 3mg) orally once daily, usually at bedtime. For ovulation induction: Treatment starts on day 2, 3, 4, or 5 of the menstrual cycle (spontaneous or induced) for 5 consecutive days. Dosage of clomiphene may be increased in subsequent cycles (e.g., 100mg) if no response, but the fixed-dose combination limits this titration. Melatonin dose is fixed.
Note: Take tablet at bedtime with a glass of water, with or without food. For ovulation induction, strictly follow the day cycle prescribed by the gynecologist. Avoid taking melatonin during daytime. Do not crush or chew.
Clomiphene competitively blocks estrogen receptors (ERs) at the level of the hypothalamus and pituitary, decreasing negative feedback. This leads to increased pulsatile secretion of GnRH, followed by increased secretion of pituitary gonadotropins (FSH and LH). The rise in FSH stimulates follicular growth and development. Melatonin, primarily secreted by the pineal gland, acts on MT1 and MT2 receptors in the suprachiasmatic nucleus to synchronize the circadian clock. In the ovary, melatonin receptors are present on granulosa cells. It is a potent antioxidant, scavenging free radicals and upregulating antioxidant enzymes like glutathione peroxidase, potentially protecting developing ovarian follicles from oxidative stress, which is implicated in poor oocyte quality and anovulation.
Pregnancy: CONTRANDICATED. Clomiphene is Pregnancy Category X. Discontinue immediately if pregnancy is confirmed. There is a theoretical risk of teratogenicity, though studies are inconclusive. Melatonin's safety in pregnancy is not established.
Driving: May impair ability to drive or operate machinery, especially at treatment initiation or if drowsiness occurs. Do not drive for at least 4-5 hours after taking melatonin.
| CYP2C9 Inhibitors (e.g., Fluconazole, Amiodarone) | Increased clomiphene levels, risk of toxicity | Moderate |
| CYP3A4 Inducers (e.g., Rifampicin, Carbamazepine) | Decreased clomiphene efficacy | Moderate |
| CYP1A2 Inhibitors (e.g., Fluvoxamine, Ciprofloxacin) | Increased melatonin levels, enhanced sedation | Moderate |
| Other CNS Depressants (e.g., Benzodiazepines, Opioids, Alcohol) | Additive sedation and impaired motor coordination | Major |
| Anticoagulants (e.g., Warfarin) | Melatonin may increase INR; monitor closely | Moderate |
| Immunosuppressants (e.g., Cyclosporine) | Melatonin may antagonize immunosuppressive effect | Moderate |
| Antidiabetic Drugs | Melatonin may impair glucose tolerance; monitor blood sugar | Moderate |
| Oral Contraceptives/HRT | May interfere with clomiphene's action | Major |
Same composition (Clomiphene (50mg) + Melatonin (3mg)), different brands: