QUARTETTE
Clinical safety rating
cautionComprehensive clinical and safety monograph for QUARTETTE (QUARTETTE).
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.
| 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. |
| Molecular Weight | 278.33 |
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. |
| 1st trimester | Contraindicated due to increased risk of congenital malformations including neural tube defects and cardiovascular anomalies. |
| 2nd trimester | Contraindicated; associated with fetal growth restriction and oligohydramnios. |
| 3rd trimester | Contraindicated; may cause premature closure of the ductus arteriosus and persistent pulmonary hypertension. |
Clinical note
Comprehensive clinical and safety monograph for QUARTETTE (QUARTETTE).
| Placental transfer | Crosses the placenta readily; achieves fetal plasma concentrations similar to maternal levels. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse effects in the nursing infant, including kernicterus and hemolytic anemia. |
| Lactation Rating | L5 - Contraindicated |
| 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. |
| Fetal Monitoring | No specific monitoring required during pregnancy as drug is contraindicated. If accidental exposure occurs, no special fetal monitoring indicated beyond standard prenatal care. |
| Fertility Effects | No permanent fertility impairment. Reversible suppression of ovulation. Normal fertility resumes upon discontinuation. |
■ 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.
| Serious Effects |
PregnancyBreastfeedingHistory of hypersensitivity to sulfonamidesSevere hepatic impairmentSevere renal impairment
| 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. |
| Food/Dietary | No specific dietary restrictions. Grapefruit juice may slightly increase estrogen levels but not clinically significant. Advise consistent intake to avoid absorption variability. |
| Clinical Pearls | QUARTETTE is a combined hormonal contraceptive containing ethinyl estradiol and levonorgestrel, with a unique 4-day placebo phase (91-day cycle) to extend menstrual suppression. For patients with breakthrough bleeding, consider shorter placebo intervals or continuous use. Assess venous thromboembolism risk factors before prescribing, especially in smokers over 35. Counsel on delayed start if initiating after day 5 of menses. |
| Patient Advice | Take one pill daily at the same time; missed pills increase pregnancy risk. · Use backup contraception (e.g., condoms) for the first 7 days if starting after day 5 of menses. · Expect lighter, less frequent periods; spotting may occur initially. · Do not skip the 4 placebo pills; they are reminder pills. |
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