AdultPediatricDosage Forms & Strengths estetrol/drospirenone tablet 14.2mg/3mg Contraception Indicated for use by females of reproductive potential to prevent pregnancy Days 1-24: 1 active tablet (3 mg drospirenone [DRSP]/14.2 mg estetrol [E4]) PO qDay, THEN Days 25-28: 1 inert tablet PO qDay Dosage Modifications Renal impairment All severities of renal impairment: Contraindicated CrCl 30-49 mL/min: Serum DRSP concentrations were ~37 higher than control group Females with renal impairment whose serum potassium is in upper reference range and are concomitantly using potassium-sparing drugs may potentially develop hyperkalemia Hepatic impairment All severities of hepatic impairment: Contraindicated Moderate: Mean exposure to DRSP was ~3x higher than females with normal liver function Severe: Not studied Dosing Considerations Initiating with no current use of hormonal contraception Females with irregular menstrual cycles: Consider pregnancy testing before initiation Days 1-24: Take 1 pink active tablet once daily starting on first day of menses Days 25-28: Take 1 white inert tablet daily Each subsequent 28-day pack: Begin on same day of week as first cycle pack (eg, on day after taking the last tablet) If not starting on first day of menses, use nonhormonal contraceptive (eg, condoms and/or spermicide) as backup until 1 active tablet has been taken daily for 7 days in a row Switching from another contraceptive method Combined oral contraceptive (COC): Start when new pack of previous COC would have started Transdermal system, vaginal insert, or injection: Start when next administration would have been scheduled Intrauterine system (IUS) or implant: Start after removal Progestin-only pill: Start after last tablet was taken Initiating after delivery (>20 weeks gestation) Do not start <4 weeks after delivery Menstrual cycles have resumed: Follow instructions for “starting estetrol/drospirenone in females with no current use of hormonal contraception” Menstrual cycles have not resumed: Consider possibility of ovulation and pregnancy; if not pregnant, use additional nonhormonal contraception for first 7 days of use Starting DRSP/E4 after delivery (>20 weeks gestation) ≤14 weeks gestation Starting ≤7 days of complete first trimester abortion or miscarriage: Use additional contraception for next 7 days Starting >7 days: Follow instructions for “starting DRSP/E4 in females with no current use of hormonal contraception” >14 weeks to ≤20 weeks gestation Start after 4 weeks following second trimester abortion or miscarriage; consider duration of pregnancy and increased risk of thromboembolism Menstrual cycles have resumed: Follow instructions for “starting DRSP/E4 in females with no current use of hormonal contraception” Menstrual cycles have not resumed: Consider possibility of ovulation and pregnancy; if not pregnant, use additional nonhormonal contraception for first 7 days of use Limitation of use May be less effective in females with a body mass index (BMI) ≥30 kg/m2; decreased effectiveness may be associated with increased BMI Dosage Forms & Strengths estetrol/drospirenone tablet 14.2mg/3mg Contraception Indicated for use by females of reproductive potential to prevent pregnancy Study was done on females of reproductive potential aged 16-50 years Days 1-24: 1 active tablet (3 mg drospirenone [DRSP]/14.2 mg estetrol [E4]) PO qDay, THEN Days 25-28: 1 inert tablet PO qDay Dosage Modifications Renal impairment All severities of renal impairment: Contraindicated CrCl 30-49 mL/min: Serum DRSP concentrations were ~37 higher than control group Females with renal impairment whose serum potassium is in upper reference range and are concomitantly using potassium-sparing drugs may potentially develop hyperkalemia Hepatic impairment All severities of hepatic impairment: Contraindicated Moderate: Mean exposure to DRSP was ~3x higher than females with normal liver function Severe: Not studied Dosing Considerations Initiating with no current use of hormonal contraception Females with irregular menstrual cycles: Consider pregnancy testing before initiation Days 1-24: Take 1 pink active tablet once daily starting on first day of menses Days 25-28: Take 1 white inert tablet daily Each subsequent 28-day pack: Begin on same day of week as first cycle pack (eg, on day after taking the last tablet) If not starting on first day of menses, use nonhormonal contraceptive (eg, condoms and/or spermicide) as backup until 1 active tablet has been taken daily for 7 days in a row Switching from another contraceptive method Combined oral contraceptive (COC): Start when new pack of previous COC would have started Transdermal system, vaginal insert, or injection: Start when next administration would have been scheduled Intrauterine system (IUS) or implant: Start after removal Progestin-only pill: Start after last tablet was taken Initiating after delivery (>20 weeks gestation) Do not start <4 weeks after delivery Menstrual cycles have resumed: Follow instructions for “starting estetrol/drospirenone in females with no current use of hormonal contraception” Menstrual cycles have not resumed: Consider possibility of ovulation and pregnancy; if not pregnant, use additional nonhormonal contraception for first 7 days of use Starting DRSP/E4 after delivery (>20 weeks gestation) ≤14 weeks gestation Starting ≤7 days of complete first trimester abortion or miscarriage: Use additional contraception for next 7 days Starting >7 days: Follow instructions for “starting DRSP/E4 in females with no current use of hormonal contraception” >14 weeks to ≤20 weeks gestation Start after 4 weeks following second trimester abortion or miscarriage; consider duration of pregnancy and increased risk of thromboembolism Menstrual cycles have resumed: Follow instructions for “starting DRSP/E4 in females with no current use of hormonal contraception” Menstrual cycles have not resumed: Consider possibility of ovulation and pregnancy; if not pregnant, use additional nonhormonal contraception for first 7 days of use Limitation of use May be less effective in females with a body mass index (BMI) ≥30 kg/m2; decreased effectiveness may be associated with increased BMI Interaction CheckerEnter a drug name and estetrol/drospirenoneNo Results No Interactions Found Interactions FoundContraindicatedSerious - Use AlternativeSignificant - Monitor CloselyMinorAll Interactions Sort By: SeverityName Due to system maintenance, the drug interactions feature you are attempting to access is temporarily unavailable. Please try again later. >10% Bleeding irregularities (9.7-10.8%) Mood disturbance (9.1-10.9%) 1-10% Headache (4.8-6.3%) Breast symptoms (5.3-5.4%) Dysmenorrhea (3.7-4.1%) Weight increased (3-3.3%) Acne (3.2-3.7%) Libido decreased/lost (1.3-2%) Depression (1.7%) Frequency Not Defined Thromboembolic event reported in a female who had been taking therapy for 75 days and had normal BMI < 25 kg/m2 Black Box Warnings Cigarette smoking and serious cardiovascular events Cigarette smoking increases risk of serious cardiovascular adverse effects from CHC use This risk increases with age, particularly in females aged >35 years, and number of cigarettes smoked CHCs, including DRSP/E4, are contraindicated in females aged ≥35 years and smoke Contraindications History of, increased risk for, or current arterial or venous thrombotic/thromboembolic diseases Examples include females with the following conditions Smoking, if aged ≥35 years Current or history of deep vein thrombosis or pulmonary embolism Cerebrovascular disease Coronary artery disease Thrombogenic valvular or thrombogenic rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease, atrial fibrillation) Inherited or acquired hypercoagulopathies Uncontrolled hypertension or hypertension with vascular disease Diabetes mellitus with hypertension or end-organ damage; or diabetes mellitus of >20 years duration Migraine headaches with aura Current or history of a hormonally-sensitive malignancy (eg, breast cancer) Hepatic adenoma, hepatocellular carcinoma, acute hepatitis, or severe (decompensated) cirrhosis Use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir Abnormal uterine bleeding with undiagnosed etiology Renal impairment Adrenal insufficiency Cautions Increased blood pressure (BP) reported in females using COCs; increase is more likely in older females with extended duration of use; monitor BP periodically and discontinue if BP rises significantly Migraine headaches with aura increase the risk for stroke; stroke risk is further increased in females who have migraine headaches with aura with use of CHCs; discontinue if new migraine headaches develop that are recurrent, persistent, or severe or increased frequency or severity of migraine headaches (which may be prodromal of a cerebrovascular event) May promote growth of any hormone receptor–positive tumor, both within and external to female reproductive tract (eg, hormone receptor–positive include melanoma, adenocarcinoma of the lung, meningioma); discontinue if a hormonally sensitive malignancy is diagnosed May cause elevated liver enzymes; withhold or permanently discontinue for persistent or significant elevation of liver enzymes CHCs increase the risk of hepatic tumors, particularly hepatic adenomas; rupture of hepatic adenomas may cause death from abdominal hemorrhage May decrease glucose tolerance; carefully monitor females with prediabetes and diabetes during therapy Females with hypertriglyceridemia or with family history may have increase serum triglyceride concentrations during use, which may increase risk of pancreatitis; consider alternative contraception Studies suggest an increased risk of developing gallbladder disease among CHC users; use of CHCs may also worsen existing gallbladder disease; females with a history of pregnancy-related cholestasis may be at an increased risk for CHC-related cholestasis; consider discontinuing treatment in females with symptomatic gallbladder disease or cholestatic disease Limited data are available on association of COCs with onset of depression or exacerbation of existing depression; monitor females with a history of depression and discontinue if depression recurs to a serious degree Causal relationship between use of CHCs and development of cervical cancer and intraepithelial neoplasia has not been clearly established Exogenous estrogens may induce or exacerbate symptoms of hereditary angioedema; avoid in females with hereditary angioedema Chloasma may occur with use, especially in females with history of chloasma gravidarum; avoid in females with a history of chloasma gravidarum or increased sensitivity to sun and/or ultraviolet radiation exposure Breast cancer Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk; studies do not show an association between ever (current or past) use of COCs and risk of breast cancer Some studies report a small increase in risk of breast cancer among current or recent users(<6 months since last use) and current users with longer duration of COC use A woman's risk depends on conditions where naturally high hormone levels persist for long periods of time including early-onset menstruation before age 12, late-onset menopause, after age 55, first child after age 30, nulliparity Bleeding irregularities and amenorrhea May experience unscheduled (breakthrough or intracyclic) bleeding and spotting, especially during first 4 months of use Bleeding irregularities may resolve over time or by changing to a different contraceptive product; if bleeding persists or occurs after previously regular cycles, evaluate for causes (eg, pregnancy, malignancy) Females may also experience absence of scheduled (withdrawal) bleeding, even if they are not pregnant; if scheduled bleeding does not occur, consider possibility of pregnancy If patient has not adhered to prescribed dosing schedule (missed 1 or 2 active tablets or started taking them on a day later than prescribed), consider possibility of pregnancy at time of the first missed period and perform appropriate diagnostic measures After discontinuation, amenorrhea or oligomenorrhea may occur, especially if these conditions were preexistent Thromboembolic disorders Before starting, evaluate any medical history or family history of thrombotic or thromboembolic disorders; consider whether history suggests an inherited or acquired hypercoagulopathy Use of CHCs increases the risk of cardiovascular events and cerebrovascular events, (eg, myocardial infarction, stroke); risk is greater among females aged >40, smokers, and females with hypertension, dyslipidemia, diabetes, or obesity; risk increases with age, particularly in females aged ≥35 years, and with number of cigarettes smoked or use of other nicotine-containing products Use of CHCs also increases the risk of venous thromboembolic events (VTEs) (eg, deep vein thrombosis, pulmonary embolism); risk of VTE is highest during first year of CHC use and when restarting hormonal contraception after a break ≥4 weeks; risk of VTE returns to baseline ~3 months after CHC discontinued Postpartum VTE VTE is increased during first 6 weeks postpartum compared with risk in nonpregnant, nonpostpartum females Risk highest in first 3 weeks postpartum; remains higher than baseline until at least 6 weeks postpartum Multiple risk factors for VTE may further increase the risk Obstetric complications may extend elevated risk up to 12 weeks postpartum Discontinue for the following Thrombotic event occurs Unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately During prolonged immobilization Hyperkalemia Contraindicated in females with conditions that predispose to hyperkalemia (eg, renal impairment, hepatic impairment, adrenal insufficiency) Females receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium concentration should have their serum potassium concentration checked during first treatment cycle and monitored Product contains drospirenone, a progestin, which has anti-mineralocorticoid activity, including potential for hyperkalemia in high-risk females, comparable to a 25-mg dose of spironolactone Drug interaction overview DRSP: CYP3A4 substrate CYP3A4 inducers Strong CYP3A4 inducers: Avoid coadministration; if unavoidable, use alternant contraceptive method (eg,