MILOPHENE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MILOPHENE (MILOPHENE).
MILOPHENE is a selective estrogen receptor modulator (SERM) that acts as an antagonist in breast tissue and agonist in bone and cardiovascular tissues. It binds competitively to estrogen receptors, inhibiting estrogen-mediated proliferation in breast cancer cells.
| Metabolism | Metabolized primarily by CYP3A4 and CYP2D6 to active metabolites (e.g., N-desmethylmilophene, 4-hydroxymilophene). Undergoes enterohepatic recirculation. |
| Excretion | Primarily renal excretion of unchanged drug (70-80%), with 10-15% as glucuronide conjugate; biliary/fecal elimination accounts for <10%. |
| Half-life | Terminal elimination half-life is 18-24 hours, supporting once-daily dosing; prolonged in renal impairment. |
| Protein binding | 92-96% bound to albumin. |
| Volume of Distribution | 0.3-0.4 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Oral: 65-75% with significant first-pass metabolism. |
| Onset of Action | Oral: 2-4 hours. |
| Duration of Action | Approximately 24 hours, aligning with once-daily regimen. |
| Molecular Weight | 485.32 |
1-2 mg/kg intravenously every 4 hours, not to exceed 100 mg per dose.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: 75% of normal dose every 6 hours; GFR 15-29 mL/min: 50% of normal dose every 8 hours; GFR <15 mL/min: 25% of normal dose every 12 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: 50% of normal dose every 6 hours; Child-Pugh Class C: contraindicated. |
| Pediatric use | Children 1 month to 12 years: 0.5-1 mg/kg intravenously every 4-6 hours, maximum 50 mg per dose; infants <1 month: 0.25-0.5 mg/kg every 6-8 hours. |
| Geriatric use | Start at 50% of adult dose, increase based on tolerance and renal function; monitor for neurotoxicity and QT prolongation. |
| 1st trimester | Teratogenic in animal studies; avoid. If essential, use only after ruling out pregnancy. |
| 2nd trimester | Limited human data; use only if benefit outweighs risk. May cause fetal harm. |
| 3rd trimester | Avoid; may cause adverse fetal effects. |
Clinical note
Comprehensive clinical and safety monograph for MILOPHENE (MILOPHENE).
| Placental transfer | Crosses placenta in animals; human data limited but presumed to transfer. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse reactions in nursing infants. Decision to discontinue nursing or drug based on importance of drug to mother. |
| Lactation Rating |
■ FDA Black Box Warning
Boxed Warning: Increased risk of thromboembolic events (deep vein thrombosis, pulmonary embolism) and stroke. Use with caution in patients with history of thromboembolic disorders.
| Serious Effects |
PregnancyBreastfeedingKnown hypersensitivity to milophene
| Precautions | Warnings: Thromboembolic events, stroke, endometrial hyperplasia/carcinoma, ovarian cysts, visual disturbances (e.g., cataracts, retinopathy), hepatic impairment, hypercalcemia in bone metastases. Monitor lipid profiles and liver function. |
| Food/Dietary | Grapefruit juice may increase clomiphene levels; avoid concurrent consumption. No specific food restrictions, but maintain a balanced diet. Limit caffeine intake as it may affect fertility. |
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| L5 (Contraindicated) |
| Teratogenic Risk | MILOPHENE is a dopamine agonist used for hyperprolactinemia. In the first trimester, there is limited human data but no evidence of increased major malformations. Risk cannot be completely excluded. In the second and third trimesters, continued use may be justified if needed. Limited studies suggest no significant increase in adverse fetal outcomes. However, dopamine agonists have been associated with fetal harm in animal studies, so cautious use is warranted throughout pregnancy. |
| Fetal Monitoring | Monitor maternal prolactin levels, blood pressure, and signs of cardiac valvulopathy. Fetal monitoring includes ultrasound for growth and anatomy if exposure occurs in the first trimester. Assess for any signs of neonatal extrapyramidal symptoms or withdrawal if used near term. |
| Fertility Effects | MILOPHENE restores ovulatory cycles and improves fertility in hyperprolactinemic women by lowering prolactin. However, treatment may also increase the risk of multiple gestations. In men, it can improve spermatogenesis. Fertility may return to normal once prolactin levels are normalized. |
| Clinical Pearls | Milophene (clomiphene citrate) is a selective estrogen receptor modulator used for ovulation induction. Monitor for ovarian hyperstimulation syndrome (OHSS) with pelvic ultrasound. Limit course duration to 6 cycles due to increased risk of ovarian cancer. Use with caution in patients with liver disease or abnormal uterine bleeding. Administer on days 3-7 of menstrual cycle for optimal response. |
| Patient Advice | Take exactly as prescribed, typically one tablet daily for 5 days starting on cycle day 3, 4, or 5. · Notify your doctor immediately if you experience severe pelvic pain, nausea, vomiting, or sudden weight gain (signs of OHSS). · Avoid pregnancy before starting treatment; use barrier contraception until instructed. · Multiple births (especially twins) occur in about 10% of pregnancies; discuss this risk. · Report any visual disturbances (blurring, spots, flashes) promptly; discontinue use if they occur. · Do not exceed 6 treatment cycles; prolonged use increases ovarian cancer risk. |