IUS) or backup nonhormonal contraceptive during coadministration and up to 28 days after discontinuing strong CYP3A4 inducer Moderate and weak CYP3A4 inducers: Use alternant or backup contraceptive method during coadministration and up to 28 days after discontinuing CYP3A inducer, unless prescribing information of specific moderate or weak CYP3A inducer indicates there is no clinically significant interaction Strong CYP3A inducers or certain moderate or weak CYP3A inducers may decrease DRSP exposure, which may lead to contraceptive failure Strong CYP3A4 inhibitors May increase drospirenone/estetrol systemic exposure Consider monitoring serum potassium concentration in patients who take a strong CYP3A4 inhibitor long-term and concomitantly with DRSP/E4 Drugs that may reduce absorption Separate administration times of DRSP/E4 and concomitant drug; refer to concomitant drug's prescribing information for additional information Drugs such as bile acid sequestrants may decrease the E4 and DRSP exposure, which may lead to contraceptive failure and/or an increased breakthrough bleeding Antidiabetic drugs Increase frequency of glucose monitoring and increase antidiabetic drug dosage, as needed, based on glucose levels DRSP/E4 may reduce blood glucose–lowering effects of antidiabetic drugs Drugs that may increase serum potassium concentration Monitor serum potassium concentration in females at increased risk for hyperkalemia DRSP/E4 may increase serum potassium concentration in females concurrently taking other drugs that may increase serum potassium Lamotrigine Adjust lamotrigine dosage as recommended by prescribing information DRSP/E4 may decrease exposure and efficacy of lamotrigine Systemic corticosteroids Follow recommendations in accordance with prescribing information of corticosteroids consider more frequent monitoring for corticosteroid adverse reactions DRSP/E4 may increase exposure and toxicities of systemic corticosteroids (owing to increased corticosteroid-binding globulin) and mineralocorticoids (owing to increased aldosterone) Hepatitis C treatment CHCs are contraindicated for use with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir (with or without dasabuvir) Discontinue DRSP/E4 before starting therapy with combination drug regimen ombitasvir/paritaprevir/ritonavir (with or without dasabuvir) May restart ~2 weeks following completion of treatment with this hepatitis C combination drug regimen During clinical trials with these hepatitis C combination drug regimens, ALT elevations >5x ULN, including some cases >20x ULN, were significantly more frequent in females using ethinyl estradiol (EE) containing drugs, such as CHCs Thyroid hormone replacement therapy Increase thyroid hormone replacement dose as needed Estrogen component may increase the serum concentrations of thyroxine-binding globulin Sex hormones Coadministration may decrease androstenedione, progesterone, and free testosterone owing to increased sex hormone-binding globulin Pregnancy Discontinue if pregnancy occurs Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (eg, cardiac anomalies, limb-reduction defects) following COC exposure before conception or during early pregnancy Animal studies Reproductive toxic studies performed with E4 alone have shown expected pharmacologic effects in animals, which are consistent with estrogen exposure Lactation Contraceptive hormones and/or metabolites are present in human milk COCs can reduce milk production in breastfeeding females; reduction may occur at any time, but less likely to occur once breastfeeding is well established When possible, advise nursing females to use other methods of contraception until breastfeeding is discontinued After oral administration of DRSP 3 mg/ethinyl estradiol 30 mcg, about 0.02% of the DRSP dose was excreted into the breast milk of postpartum females within 24 hr; results in a potential maximal daily dose <1 mcg DRSP in an infantPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Estetrol (E4): Synthetic analogue of a native estrogen present during pregnancy, that is selective for nuclear estrogen receptor-alpha (ER-alpha) and ER-beta; treatment results in decrease of follicle-stimulating hormone and luteinizing hormone, ultimately leading to ovulation suppression Drospirenone: Progestin; spironolactone analogue with anti-mineralocorticoid and anti-androgenic activity that provides contraception primarily by suppressing ovulation Absorption Peak plasma concentration E4: 17.9 ng/mL DRSP: 48.7 ng/mL Peak plasma time E4: 0.5 hr DRSP: 1 hr AUC E4: 59.1 ng·hr/mL DRSP: 519 ng·hr/mL Time to steady-state E4: 4 days DRSP: 10 days Effects of high-fat meal (relative to fasting) Geometric mean peak plasma concentration ratio: 0.5 (E4); 0.75 (DRSP) Geometric mean AUC ratio: 1.01 (E4); 1.08 (DRSP) Distribution Protein bound E4: 46-50% DRSP: 95-97% Metabolism E4 Phase 2 metabolism to form glucuronide and sulphate conjugates which have negligible in-vitro estrogenic activity In vitro studies show that UGT2B7 is dominant UGT isoform that catalyzes the formation of E4-16-glucuronide DRSP Metabolized by CYP3A4 Two main metabolites (not active): acid form of DRSP generated by opening of lactone ring and 4,5 dihydrodrospirenone formed by reduction followed by sulfation Elimination Half-life E4: 27 hr (bound to albumin) DRSP: 34 hr Excretion E4: Urine (69%); feces (22%; 100% unchanged) DRSP: Urine (38%); feces (44%) Oral Administration Take at the same time every day and in the order directed by blister pack May take with or without food Swallow both pink pills and white pills whole Missed dose Missed 1 pink active tablet Take missed dose as soon as possible and take next tablet at scheduled time, even if 2 active tablets are taken in 1 day Continue taking 1 tablet a day until pack is finished Missed ≥2 pink active tablets in Week 1 or 2 Take missed dose as soon as possible and take next tablet at scheduled time, even if 2 active tablets are taken in 1 day and discard other missed tablets Continue taking 1 tablet a day until pack is finished Use additional nonhormonal contraception as backup until pink tablets have been taken for 7 consecutive days Missed ≥2 pink active tablets in Week 3 Take missed dose as soon as possible and take next tablet at scheduled time, even if 2 active tablets are taken in 1 day and discard other missed tablets Finish active tablets and discard inactive tablets in pack; start a new pack of tablets the next day Use additional nonhormonal contraception as backup until pink tablets have been taken for 7 consecutive days Missed ≥1 white inert tablets Skip missed doses and continue taking 1 tablet a day until pack is finished After vomiting or acute diarrhea Vomiting or acute diarrhea occurs within 3-4 hr after taking active tablet: Take new active tablet (scheduled for next day) as soon as possible; if possible, take new tablet [wrap]within 12 hr of next scheduled dose Missed >2 tablets: Follow advice above concerning missed tablets Storage Store at 20-25°C; excursion permitted to 15-30°C (50-86°F) Dispose unused medication via a take-back option if available Otherwise, follow FDA instructions for disposing medication in household trash, www.fda.gov/drugdisposal; do NOT flush down the toilet No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. 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