MILOPHENE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MILOPHENE (MILOPHENE).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MILOPHENE (MILOPHENE).

Breastfeeding

MILOPHENE is excreted into human breast milk. The M/P ratio is unknown but assumed to be low based on molecular weight and protein binding. Due to potential adverse effects on the infant (e.g., dopamine receptor blockade), breastfeeding is not recommended during therapy. Alternative treatments or cessation of breastfeeding should be considered.

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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Contraindications: Hypersensitivity to milophene or any component; pregnancy (Category X); history of thromboembolic disease (e.g., DVT, PE); undiagnosed abnormal genital bleeding; hepatic impairment (severe); concurrent use of anticoagulants.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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MILOPHENE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MILOPHENE (MILOPHENE).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MILOPHENE (MILOPHENE).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ 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.