A fixed-dose combination of a selective estrogen receptor modulator (SERM) and a pineal 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 hormone that regulates sleep-wake cycles and has been studied for its potential role in improving oocyte quality and follicular development by acting as an antioxidant and modulating reproductive hormone rhythms. This combination is used in the management of anovulatory infertility, particularly in cases where sleep disturbances or circadian rhythm disruptions may be a contributing factor.
Adult: One tablet (Clomiphene 100mg + Melatonin 3mg) orally once daily, at bedtime, for 5 days, starting on day 2, 3, 4, or 5 of the menstrual cycle (spontaneous or induced). The melatonin component dictates bedtime administration. Treatment courses should not exceed 3-6 cycles.
Note: Take at bedtime with a glass of water. For fertility, start on a specific day of the cycle as directed by the gynecologist. Avoid high-fat meals close to dosing as it may delay melatonin absorption. Do not crush or chew.
Clomiphene competitively blocks estrogen receptors (ERs) in the hypothalamus, interrupting the normal negative feedback loop of estrogen. This is misinterpreted as low estrogen levels, leading to increased pulsatile secretion of Gonadotropin-Releasing Hormone (GnRH). This, in turn, stimulates the anterior pituitary to release Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH), promoting follicular growth and ovulation. Melatonin, primarily through MT1 and MT2 receptors in the suprachiasmatic nucleus, synchronizes the circadian rhythm. In the ovary, melatonin acts as a potent free radical scavenger, reducing oxidative stress in follicular fluid, which may improve oocyte quality and granulosa cell function. It may also modulate aromatase activity and progesterone production.
Pregnancy: CONTRANDICATED. Clomiphene is Pregnancy Category X. It may have teratogenic effects. Treatment must be stopped once pregnancy is confirmed. The combination is used to achieve pregnancy, not to maintain it.
Driving: May impair ability to drive or operate machinery, especially at night after taking the dose (due to melatonin's sedative effect). Do not drive for at least 4-5 hours after ingestion.
| CYP2D6 Inhibitors (e.g., Fluoxetine, Paroxetine) | Increased clomiphene levels, potentially increasing toxicity. | Moderate |
| CYP3A4 Inducers (e.g., Rifampicin, Carbamazepine) | Decreased clomiphene efficacy. | Moderate |
| CYP1A2 Inhibitors (e.g., Fluvoxamine, Ciprofloxacin) | Markedly increased melatonin exposure, causing excessive sedation. | Major |
| Other Hypnotics/Sedatives (e.g., Benzodiazepines, Zolpidem) | Additive CNS depression with melatonin. | Major |
| Anticoagulants (e.g., Warfarin) | Clomiphene may potentiate anticoagulant effect; monitor INR. | Moderate |
| Thyroid Hormones | Melatonin may inhibit thyroid-stimulating hormone (TSH) secretion. | Moderate |
| Immunosuppressants (e.g., Cyclosporine) | Melatonin may stimulate immune function, potentially reducing efficacy. | Moderate |
| Antihypertensives (e.g., Nifedipine, Verapamil) | Melatonin may potentiate hypotensive effect. | Moderate |
| Oral Contraceptives | Will interfere with the intended ovulation induction effect of clomiphene. | Major |
Same composition (Clomiphene (100mg) + Melatonin (3mg)), different brands: