MODRASTANE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MODRASTANE (MODRASTANE).

How it works

Selective antagonist of mineralocorticoid receptors, blocking the binding of aldosterone and other corticosteroids, leading to increased renal excretion of sodium and water while retaining potassium.

What the body does with it

Metabolism	Primarily hepatic via CYP3A4; major metabolites include canrenone and 7α-thiomethylspironolactone.
Excretion	Renal excretion of unchanged drug accounts for 30-40%; biliary/fecal excretion accounts for 50-60%, with 10-20% as glucuronide conjugates.
Half-life	Terminal elimination half-life is 12-15 hours; allows once-daily dosing after steady state achieved within 3-5 days.
Protein binding	98% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8-1.2 L/kg; indicates extensive tissue distribution, exceeding total body water.
Bioavailability	Oral: 45-60% (first-pass metabolism); IV: 100%.
Onset of Action	Oral: 30-60 minutes; IV bolus: 5-10 minutes.
Duration of Action	Oral: 12-24 hours; IV: 6-12 hours. Clinical effect diminishes after 12 hours, supporting once-daily oral dosing.

Classification & Brands

Dosing & administration

100 mg orally twice daily.

Dosage form	CAPSULE
Renal impairment	GFR 30-89 mL/min: no adjustment. GFR <30 mL/min: contraindicated.
Liver impairment	Child-Pugh A or B: no adjustment. Child-Pugh C: contraindicated.
Pediatric use	Not approved for pediatric use.
Geriatric use	Start at 50 mg twice daily; increase based on tolerability.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MODRASTANE (MODRASTANE).

Breastfeeding	Modrastane is excreted into human breast milk; M/P ratio not determined. Contraindicated in breastfeeding due to potential for serious adverse effects in the nursing infant, including adrenal suppression and carcinogenicity.
Teratogenic Risk	Modrastane is contraindicated in pregnancy due to teratogenicity. First trimester: High risk of major congenital malformations, including neural tube defects, cardiovascular anomalies, and cleft palate. Second and third trimesters: Risk of oligohydramnios, fetal renal impairment, and skull ossification defects.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hyperkalemia; Addison's disease; severe renal impairment (eGFR <30 mL/min); concomitant use with eplerenone; anuria; hypersensitivity.

Clinical Precautions

Precautions

Hyperkalemia risk, especially with renal impairment or concurrent potassium supplements/ACE inhibitors; caution in hepatic impairment; can cause gynecomastia and menstrual irregularities; monitor electrolytes and renal function.

Clinical Tips & Counseling

Drug interactions

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MODRASTANE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MODRASTANE (MODRASTANE).

How it works

Selective antagonist of mineralocorticoid receptors, blocking the binding of aldosterone and other corticosteroids, leading to increased renal excretion of sodium and water while retaining potassium.

What the body does with it

Metabolism	Primarily hepatic via CYP3A4; major metabolites include canrenone and 7α-thiomethylspironolactone.
Excretion	Renal excretion of unchanged drug accounts for 30-40%; biliary/fecal excretion accounts for 50-60%, with 10-20% as glucuronide conjugates.
Half-life	Terminal elimination half-life is 12-15 hours; allows once-daily dosing after steady state achieved within 3-5 days.
Protein binding	98% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8-1.2 L/kg; indicates extensive tissue distribution, exceeding total body water.
Bioavailability	Oral: 45-60% (first-pass metabolism); IV: 100%.
Onset of Action	Oral: 30-60 minutes; IV bolus: 5-10 minutes.
Duration of Action	Oral: 12-24 hours; IV: 6-12 hours. Clinical effect diminishes after 12 hours, supporting once-daily oral dosing.

Classification & Brands

Dosing & administration

100 mg orally twice daily.

Dosage form	CAPSULE
Renal impairment	GFR 30-89 mL/min: no adjustment. GFR <30 mL/min: contraindicated.
Liver impairment	Child-Pugh A or B: no adjustment. Child-Pugh C: contraindicated.
Pediatric use	Not approved for pediatric use.
Geriatric use	Start at 50 mg twice daily; increase based on tolerability.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MODRASTANE (MODRASTANE).

Breastfeeding	Modrastane is excreted into human breast milk; M/P ratio not determined. Contraindicated in breastfeeding due to potential for serious adverse effects in the nursing infant, including adrenal suppression and carcinogenicity.
Teratogenic Risk	Modrastane is contraindicated in pregnancy due to teratogenicity. First trimester: High risk of major congenital malformations, including neural tube defects, cardiovascular anomalies, and cleft palate. Second and third trimesters: Risk of oligohydramnios, fetal renal impairment, and skull ossification defects.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hyperkalemia; Addison's disease; severe renal impairment (eGFR <30 mL/min); concomitant use with eplerenone; anuria; hypersensitivity.