MIFEPRISTONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MIFEPRISTONE (MIFEPRISTONE).

How it works

Progesterone receptor antagonist; also has weak glucocorticoid receptor antagonist activity.

What the body does with it

Metabolism	Hepatic via CYP3A4; also metabolized to mono-demethylated and di-demethylated metabolites.
Excretion	Primarily fecal (83%) via biliary excretion; renal excretion accounts for approximately 9% of the dose, mainly as metabolites.
Half-life	Terminal elimination half-life is 18-30 hours (mean ~25 hours) in the elimination phase; however, a prolonged terminal half-life of up to 54 hours has been observed due to slow release from target tissues, which is clinically relevant for prolonged antiprogestogenic effects.
Protein binding	98% bound to plasma proteins, primarily to alpha-1-acid glycoprotein and albumin.
Volume of Distribution	Estimated volume of distribution is 1.5-2.0 L/kg, indicating extensive tissue distribution, particularly to reproductive organs and fat.
Bioavailability	Oral bioavailability is 69% (range 40-80%) due to first-pass metabolism; no other routes are clinically relevant.
Onset of Action	Oral: Antiprogesterone effect begins within 1-2 hours; cervical ripening and uterine contractions occur within 24-48 hours when used in combination with a prostaglandin for pregnancy termination.
Duration of Action	Antiprogestogenic effects persist for 24-48 hours after a single dose; the full abortifacient effect requires sequential administration of a prostaglandin analog (e.g., misoprostol) within 48 hours. Duration of action is dose-dependent and lasts up to 14 days for glucocorticoid receptor antagonism.

Classification & Brands

Dosing & administration

Oral, 600 mg single dose followed by oral misoprostol 400 mcg 48 hours later for termination of pregnancy up to 49 days gestation.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m2), use with caution.
Liver impairment	Contraindicated in chronic adrenal failure and severe hepatic impairment (Child-Pugh class C). No specific dosing recommendations for mild to moderate hepatic impairment, use with caution.
Pediatric use	Not approved for pediatric use. Safety and efficacy not established.
Geriatric use	No specific dosage adjustments recommended; limited data in patients >65 years. Use with caution due to potential for comorbid conditions.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MIFEPRISTONE (MIFEPRISTONE).

Breastfeeding	No human data; M/P ratio unknown. Mifepristone is lipophilic and may be excreted into breast milk; potential adverse effects in nursing infant. Use with caution, avoid if possible.
Teratogenic Risk	First trimester: Mifepristone is contraindicated for induction of abortion; use causes fetal demise. Second/third trimester: No approved use; fetal exposure may cause late abortion or preterm labor. Malformation risk not systematically studied due to its abortifacient mechanism.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Mifepristone must be administered under the supervision of a qualified physician who can assess gestational age and diagnose ectopic pregnancy. Patients must be informed of the risks of incomplete abortion, heavy bleeding, and infection. A plan for surgical evacuation in case of failed abortion must be in place.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Confirmed or suspected ectopic pregnancy","IUD in place (must be removed before use)","Chronic adrenal failure","Long-term corticosteroid therapy","Hemorrhagic disorders or concurrent anticoagulant therapy","Inherited porphyria","Allergy to mifepristone or misoprostol"]

Clinical Precautions

Precautions

["Risk of serious or fatal hemorrhage requiring blood transfusion and emergency surgery","Risk of serious bacterial infection including septic shock","Ectopic pregnancy must be excluded before use","Vaginal bleeding requiring curettage may occur","Patient must be able to return for follow-up visits"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

MIFEPRISTONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MIFEPRISTONE (MIFEPRISTONE).

How it works

Progesterone receptor antagonist; also has weak glucocorticoid receptor antagonist activity.

What the body does with it

Metabolism	Hepatic via CYP3A4; also metabolized to mono-demethylated and di-demethylated metabolites.
Excretion	Primarily fecal (83%) via biliary excretion; renal excretion accounts for approximately 9% of the dose, mainly as metabolites.
Half-life	Terminal elimination half-life is 18-30 hours (mean ~25 hours) in the elimination phase; however, a prolonged terminal half-life of up to 54 hours has been observed due to slow release from target tissues, which is clinically relevant for prolonged antiprogestogenic effects.
Protein binding	98% bound to plasma proteins, primarily to alpha-1-acid glycoprotein and albumin.
Volume of Distribution	Estimated volume of distribution is 1.5-2.0 L/kg, indicating extensive tissue distribution, particularly to reproductive organs and fat.
Bioavailability	Oral bioavailability is 69% (range 40-80%) due to first-pass metabolism; no other routes are clinically relevant.
Onset of Action	Oral: Antiprogesterone effect begins within 1-2 hours; cervical ripening and uterine contractions occur within 24-48 hours when used in combination with a prostaglandin for pregnancy termination.
Duration of Action	Antiprogestogenic effects persist for 24-48 hours after a single dose; the full abortifacient effect requires sequential administration of a prostaglandin analog (e.g., misoprostol) within 48 hours. Duration of action is dose-dependent and lasts up to 14 days for glucocorticoid receptor antagonism.

Classification & Brands

Dosing & administration

Oral, 600 mg single dose followed by oral misoprostol 400 mcg 48 hours later for termination of pregnancy up to 49 days gestation.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m2), use with caution.
Liver impairment	Contraindicated in chronic adrenal failure and severe hepatic impairment (Child-Pugh class C). No specific dosing recommendations for mild to moderate hepatic impairment, use with caution.
Pediatric use	Not approved for pediatric use. Safety and efficacy not established.
Geriatric use	No specific dosage adjustments recommended; limited data in patients >65 years. Use with caution due to potential for comorbid conditions.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MIFEPRISTONE (MIFEPRISTONE).

Breastfeeding	No human data; M/P ratio unknown. Mifepristone is lipophilic and may be excreted into breast milk; potential adverse effects in nursing infant. Use with caution, avoid if possible.
Teratogenic Risk	First trimester: Mifepristone is contraindicated for induction of abortion; use causes fetal demise. Second/third trimester: No approved use; fetal exposure may cause late abortion or preterm labor. Malformation risk not systematically studied due to its abortifacient mechanism.
Fetal Monitoring