DROSPIRENONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DROSPIRENONE (DROSPIRENONE).

How it works

Spironolactone analog that antagonizes aldosterone at the mineralocorticoid receptor, leading to increased sodium and water excretion and potassium retention. Also has antiandrogenic activity by blocking androgen receptors and decreasing ovarian androgen production via inhibition of gonadotropin release.

What the body does with it

Metabolism	Extensively metabolized via CYP3A4 to inactive metabolites; minor contribution from CYP1A1 and CYP2C19. Undergoes hepatic glucuronidation.
Excretion	Renal: ~50% (as metabolites; <10% unchanged); Fecal: ~40-50% (as metabolites; bile-mediated); Urinary and fecal elimination account for >95% of an oral dose.
Half-life	Terminal elimination half-life: ~30-35 hours (range 25-40 h); significant clinical accumulation occurs after repeated dosing, requiring 10-14 days to reach steady state.
Protein binding	97% bound to serum albumin; does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CBG).
Volume of Distribution	~4 L/kg (apparent Vd 4 L/kg), indicating extensive distribution into extravascular tissues, including breast milk.
Bioavailability	Oral: ~76% (absolute bioavailability) due to first-pass metabolism; food does not significantly affect absorption.
Onset of Action	Oral: clinical contraceptive effect begins within 24 hours of first dose if taken on day 1 of menstrual cycle; 7 days of consecutive dosing required for full contraceptive efficacy if started later.
Duration of Action	Oral: contraceptive effect persists for the duration of daily dosing; after discontinuation, ovulation returns within 1-2 weeks (contraceptive effect ends within 7 days of last pill).

Classification & Brands

Dosing & administration

3 mg orally once daily.

Dosage form	TABLET, CHEWABLE
Renal impairment	Contraindicated in GFR <30 mL/min/1.73m2. No adjustment for mild-to-moderate impairment.
Liver impairment	Contraindicated in Child-Pugh Class C. Not recommended in Class B.
Pediatric use	Not established for use in pediatric patients.
Geriatric use	Use with caution; increased risk of hyperkalemia in elderly with impaired renal function.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DROSPIRENONE (DROSPIRENONE).

Breastfeeding	Excreted in breast milk in low amounts; M/P ratio not established. Caution advised. Use only if clearly needed, consider alternative contraception.
Teratogenic Risk	Category X. Contraindicated in pregnancy. First trimester: increased risk of congenital anomalies (e.g., cardiovascular, neural tube defects). Second/third trimesters: potential for fetal harm (e.g., masculinization of female fetus due to antiandrogenic activity).
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Drospirenone-containing oral contraceptives may increase the risk of venous thromboembolism (VTE) compared to those containing levonorgestrel or other progestins. Smoking increases this risk, especially in women over 35.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Breast cancer or other estrogen-sensitive neoplasia","Active liver disease or history of hepatitis with impaired liver function","Renal impairment (CrCl <30 mL/min)","Adrenal insufficiency","Known hyperkalemia","Pregnancy","Hypersensitivity to drospirenone or any component","Current or history of DVT/PE or cerebrovascular disease","Migraine with aura in women over 35"]

Clinical Precautions

Precautions

["Increased risk of VTE, especially in smokers and women with BMI ≥30","Hyperkalemia risk in patients with renal impairment, adrenal insufficiency, or concomitant use of potassium-sparing diuretics, ACE inhibitors, ARBs, NSAIDs, or heparin","Avoid in patients with liver disease, active DVT/PE, or cerebrovascular disease","May decrease glucose tolerance; monitor in diabetics","Discontinue if jaundice or visual disturbances occur"]

Clinical Tips & Counseling

Drug interactions

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DROSPIRENONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DROSPIRENONE (DROSPIRENONE).

How it works

What the body does with it

Metabolism	Extensively metabolized via CYP3A4 to inactive metabolites; minor contribution from CYP1A1 and CYP2C19. Undergoes hepatic glucuronidation.
Excretion	Renal: ~50% (as metabolites; <10% unchanged); Fecal: ~40-50% (as metabolites; bile-mediated); Urinary and fecal elimination account for >95% of an oral dose.
Half-life	Terminal elimination half-life: ~30-35 hours (range 25-40 h); significant clinical accumulation occurs after repeated dosing, requiring 10-14 days to reach steady state.
Protein binding	97% bound to serum albumin; does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CBG).
Volume of Distribution	~4 L/kg (apparent Vd 4 L/kg), indicating extensive distribution into extravascular tissues, including breast milk.
Bioavailability	Oral: ~76% (absolute bioavailability) due to first-pass metabolism; food does not significantly affect absorption.
Onset of Action	Oral: clinical contraceptive effect begins within 24 hours of first dose if taken on day 1 of menstrual cycle; 7 days of consecutive dosing required for full contraceptive efficacy if started later.
Duration of Action	Oral: contraceptive effect persists for the duration of daily dosing; after discontinuation, ovulation returns within 1-2 weeks (contraceptive effect ends within 7 days of last pill).

Classification & Brands

Dosing & administration

3 mg orally once daily.

Dosage form	TABLET, CHEWABLE
Renal impairment	Contraindicated in GFR <30 mL/min/1.73m2. No adjustment for mild-to-moderate impairment.
Liver impairment	Contraindicated in Child-Pugh Class C. Not recommended in Class B.
Pediatric use	Not established for use in pediatric patients.
Geriatric use	Use with caution; increased risk of hyperkalemia in elderly with impaired renal function.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DROSPIRENONE (DROSPIRENONE).

Breastfeeding	Excreted in breast milk in low amounts; M/P ratio not established. Caution advised. Use only if clearly needed, consider alternative contraception.
Teratogenic Risk	Category X. Contraindicated in pregnancy. First trimester: increased risk of congenital anomalies (e.g., cardiovascular, neural tube defects). Second/third trimesters: potential for fetal harm (e.g., masculinization of female fetus due to antiandrogenic activity).
Fetal Monitoring