SEROPHENE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SEROPHENE (SEROPHENE).

How it works

Selective estrogen receptor modulator (SERM); induces ovulation by blocking estrogen negative feedback on the hypothalamus, increasing GnRH and FSH secretion, stimulating ovarian follicle development.

What the body does with it

Metabolism	Hepatic, primarily via CYP3A4; enterohepatic recirculation; eliminated in feces and urine.
Excretion	Clomiphene and its metabolites are primarily excreted in feces (about 51%) via biliary elimination. Approximately 30% is excreted in urine. A small amount is excreted in breast milk.
Half-life	The terminal elimination half-life of clomiphene is approximately 5–7 days for the zu-isomer and 8–14 days for the en-isomer. This prolonged half-life allows for once-daily dosing and may lead to accumulation when dosed repeatedly.
Protein binding	Clomiphene is highly protein bound (>99%) to albumin and likely other serum proteins.
Volume of Distribution	The apparent volume of distribution is very large, estimated >1000 L (approximately 14 L/kg). This indicates extensive tissue distribution and storage, particularly in the liver and adipose tissue.
Bioavailability	Clomiphene is well absorbed orally, with bioavailability estimated at >90% based on urinary excretion data. It undergoes first-pass metabolism, but the oral bioavailability is high.
Onset of Action	Clinical effect (ovulation induction) typically occurs 5–10 days after a course of therapy (e.g., 50 mg daily for 5 days), with ovulation usually occurring about 5–10 days after the last dose.
Duration of Action	The effect on ovulation can persist for up to 6 weeks after a single course. The drug's long half-life may cause prolonged effects and multiple ovulatory cycles if pregnancy does not occur.

Classification & Brands

Dosing & administration

50 mg orally once daily for 5 days, starting on day 5 of menstrual cycle. May increase to 100 mg daily in subsequent cycles if ovulation not achieved.

Dosage form	TABLET
Renal impairment	No specific dose adjustments recommended. Use with caution in patients with renal impairment as drug is primarily hepatically cleared.
Liver impairment	Contraindicated in patients with liver disease or history of hepatic dysfunction. No dose adjustment possible; do not use in Child-Pugh class B or C.
Pediatric use	Not indicated for use in pediatric patients. Safety and efficacy not established.
Geriatric use	Not indicated for use in postmenopausal women. No specific geriatric dosing available.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SEROPHENE (SEROPHENE).

Breastfeeding	Clomiphene is excreted into human milk in small amounts; the M/P ratio is unknown. It may decrease milk production. Breastfeeding is not recommended during treatment due to potential for infant exposure and effects on lactation.
Teratogenic Risk	Clomiphene citrate (Serophene) is contraindicated in pregnancy. It carries a risk of fetal harm if administered during pregnancy, with potential for neural tube defects, cleft palate, and other congenital anomalies. There is an increased incidence of multiple gestations and associated complications. Use during pregnancy should be avoided.

Warnings & precautions

■ FDA Black Box Warning

Not for use in patients with pre-existing liver disease or abnormal uterine bleeding of undetermined etiology. Pregnancy category X; may cause fetal harm.

Side Effect Profile

Serious Effects

Absolute Contraindications

Pregnancy; known liver disease (including past history); abnormal uterine bleeding of undetermined etiology; ovarian cyst not due to polycystic ovary syndrome; hypersensitivity to clomiphene or any component.

Clinical Precautions

Precautions

Risk of multiple pregnancy (7-10% twins, <1% higher order); ovarian hyperstimulation syndrome (OHSS); visual disturbances (blurring, spots) may occur, discontinue if develop; ovarian enlargement; hepatic impairment; endometrial hyperplasia/cancer risk with prolonged use.

Clinical Tips & Counseling

Drug interactions

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SEROPHENE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SEROPHENE (SEROPHENE).

How it works

What the body does with it

Metabolism	Hepatic, primarily via CYP3A4; enterohepatic recirculation; eliminated in feces and urine.
Excretion	Clomiphene and its metabolites are primarily excreted in feces (about 51%) via biliary elimination. Approximately 30% is excreted in urine. A small amount is excreted in breast milk.
Half-life	The terminal elimination half-life of clomiphene is approximately 5–7 days for the zu-isomer and 8–14 days for the en-isomer. This prolonged half-life allows for once-daily dosing and may lead to accumulation when dosed repeatedly.
Protein binding	Clomiphene is highly protein bound (>99%) to albumin and likely other serum proteins.
Volume of Distribution	The apparent volume of distribution is very large, estimated >1000 L (approximately 14 L/kg). This indicates extensive tissue distribution and storage, particularly in the liver and adipose tissue.
Bioavailability	Clomiphene is well absorbed orally, with bioavailability estimated at >90% based on urinary excretion data. It undergoes first-pass metabolism, but the oral bioavailability is high.
Onset of Action	Clinical effect (ovulation induction) typically occurs 5–10 days after a course of therapy (e.g., 50 mg daily for 5 days), with ovulation usually occurring about 5–10 days after the last dose.
Duration of Action	The effect on ovulation can persist for up to 6 weeks after a single course. The drug's long half-life may cause prolonged effects and multiple ovulatory cycles if pregnancy does not occur.

Classification & Brands

Dosing & administration

50 mg orally once daily for 5 days, starting on day 5 of menstrual cycle. May increase to 100 mg daily in subsequent cycles if ovulation not achieved.

Dosage form	TABLET
Renal impairment	No specific dose adjustments recommended. Use with caution in patients with renal impairment as drug is primarily hepatically cleared.
Liver impairment	Contraindicated in patients with liver disease or history of hepatic dysfunction. No dose adjustment possible; do not use in Child-Pugh class B or C.
Pediatric use	Not indicated for use in pediatric patients. Safety and efficacy not established.
Geriatric use	Not indicated for use in postmenopausal women. No specific geriatric dosing available.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SEROPHENE (SEROPHENE).

Breastfeeding	Clomiphene is excreted into human milk in small amounts; the M/P ratio is unknown. It may decrease milk production. Breastfeeding is not recommended during treatment due to potential for infant exposure and effects on lactation.
Teratogenic Risk	Clomiphene citrate (Serophene) is contraindicated in pregnancy. It carries a risk of fetal harm if administered during pregnancy, with potential for neural tube defects, cleft palate, and other congenital anomalies. There is an increased incidence of multiple gestations and associated complications. Use during pregnancy should be avoided.

Warnings & precautions

■ FDA Black Box Warning

Not for use in patients with pre-existing liver disease or abnormal uterine bleeding of undetermined etiology. Pregnancy category X; may cause fetal harm.