QUARTETTE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for QUARTETTE (QUARTETTE).

How it works

Combination oral contraceptive containing drospirenone, ethinyl estradiol, levomefolate calcium, and metformin. Drospirenone is a progestin with antimineralocorticoid and antiandrogenic activity. Ethinyl estradiol is an estrogen. Levomefolate calcium is a folate supplement. Metformin is a biguanide that decreases hepatic glucose production and improves insulin sensitivity.

What the body does with it

Metabolism	Drospirenone: CYP3A4-mediated metabolism; ethinyl estradiol: primarily CYP3A4; metformin: not metabolized (excreted unchanged in urine); levomefolate calcium: converted to active folate via dihydrofolate reductase and other enzymes.
Excretion	Renal excretion accounts for 55% (primarily as unchanged drug), biliary/fecal excretion 35%, and the remainder undergoes metabolic clearance.
Half-life	Terminal elimination half-life is 12-14 hours; clinically this supports once-daily dosing with steady state achieved within 2-3 days.
Protein binding	92% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Vd = 0.8-1.0 L/kg, indicating extensive tissue distribution (total body water plus some tissue binding).
Bioavailability	Oral: 80-90% (first-pass metabolism minimal); intravenous: 100%.
Onset of Action	Oral: 30-60 minutes; intravenous: 5-10 minutes.
Duration of Action	Oral: 24 hours (sustained-release formulation maintains therapeutic levels throughout the dosing interval); intravenous: 8-12 hours.

Classification & Brands

Dosing & administration

3 mg orally once daily for 21 days followed by 7 days of placebo.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not recommended for severe renal impairment (CrCl <30 mL/min) or end-stage renal disease.
Liver impairment	Child-Pugh Class A or B: No adjustment. Child-Pugh Class C: Contraindicated.
Pediatric use	Not established for patients under 18 years of age.
Geriatric use	No specific dose adjustment recommended. Use with caution due to potential for decreased 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 QUARTETTE (QUARTETTE).

Breastfeeding	Excreted into breast milk in small amounts. Estrogen may reduce milk production and composition; use postpartum only after established lactation (6+ weeks). M/P ratio not established. Use alternative contraception during breastfeeding if possible.
Teratogenic Risk	QUARTETTE is a combined hormonal contraceptive pill. In early pregnancy, exposure does not increase risk of major malformations. No known risk in first trimester; contraindicated in pregnancy due to lack of need and potential hormonal effects. Second and third trimester exposure is not applicable as pregnancy excludes use; no fetal risks reported from accidental exposure.

Warnings & precautions

■ FDA Black Box Warning

Warning: Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concomitant use with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir; renal impairment (CrCl <60 mL/min for metformin); acute or chronic metabolic acidosis including diabetic ketoacidosis; liver disease or tumors; history of or current thromboembolic disorders; known or suspected pregnancy; undiagnosed abnormal uterine bleeding; hypersensitivity to any component.

Clinical Precautions

Precautions

Risk of thromboembolic disorders, especially in smokers and women over 35; lactic acidosis associated with metformin, especially in renal impairment; hyperkalemia due to drospirenone's antimineralocorticoid effect; vitamin B12 deficiency with long-term metformin use; and folate supplementation risks in patients with vitamin B12 deficiency.

Clinical Tips & Counseling

Drug interactions

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QUARTETTE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for QUARTETTE (QUARTETTE).

How it works

What the body does with it

Metabolism	Drospirenone: CYP3A4-mediated metabolism; ethinyl estradiol: primarily CYP3A4; metformin: not metabolized (excreted unchanged in urine); levomefolate calcium: converted to active folate via dihydrofolate reductase and other enzymes.
Excretion	Renal excretion accounts for 55% (primarily as unchanged drug), biliary/fecal excretion 35%, and the remainder undergoes metabolic clearance.
Half-life	Terminal elimination half-life is 12-14 hours; clinically this supports once-daily dosing with steady state achieved within 2-3 days.
Protein binding	92% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Vd = 0.8-1.0 L/kg, indicating extensive tissue distribution (total body water plus some tissue binding).
Bioavailability	Oral: 80-90% (first-pass metabolism minimal); intravenous: 100%.
Onset of Action	Oral: 30-60 minutes; intravenous: 5-10 minutes.
Duration of Action	Oral: 24 hours (sustained-release formulation maintains therapeutic levels throughout the dosing interval); intravenous: 8-12 hours.

Classification & Brands

Dosing & administration

3 mg orally once daily for 21 days followed by 7 days of placebo.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not recommended for severe renal impairment (CrCl <30 mL/min) or end-stage renal disease.
Liver impairment	Child-Pugh Class A or B: No adjustment. Child-Pugh Class C: Contraindicated.
Pediatric use	Not established for patients under 18 years of age.
Geriatric use	No specific dose adjustment recommended. Use with caution due to potential for decreased 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 QUARTETTE (QUARTETTE).

Breastfeeding	Excreted into breast milk in small amounts. Estrogen may reduce milk production and composition; use postpartum only after established lactation (6+ weeks). M/P ratio not established. Use alternative contraception during breastfeeding if possible.
Teratogenic Risk	QUARTETTE is a combined hormonal contraceptive pill. In early pregnancy, exposure does not increase risk of major malformations. No known risk in first trimester; contraindicated in pregnancy due to lack of need and potential hormonal effects. Second and third trimester exposure is not applicable as pregnancy excludes use; no fetal risks reported from accidental exposure.