Estetrol-Drospirenone

Estetrol-Drospirenone is a oral contraceptive used by females to prevent pregnancy. 

• Estetrol-Drospirenone is available under the following different brand names: Nextstellis

Common side effects of Estetrol-Drospirenone include:

• Irregular vaginal bleeding,
• Mood disturbance,
• Headache,
• Breast enlargement, swelling, pain, tenderness,
• Painful menstrual periods,
• Acne,
• Weight gain, and
• Decreased sex drive

Serious side effects of Estetrol-Drospirenone include:

• Absent, missed, or irregular menstrual periods
• Anger
• Anxiety
• Breast discomfort, enlargement, fullness, pain, soreness, swelling, or tenderness
• Chest pain or discomfort
• Confusion about identity, place, and time
• Cramps
• Difficulty in speaking
• Discouragement
• Dizziness or lightheadedness
• Double vision
• Dry mouth
• Fainting
• Fast or pounding heartbeat
• Feeling sad or empty
• Headache
• Headache, severe and non-menstrual
• Heavy bleeding
• Heavy non-menstrual vaginal bleeding
• Inability to move the arms, legs, or facial muscles
• Inability to speak
• Irregular heartbeat
• Irritability
• Lack of appetite
• Longer or heavier menstrual periods
• Loss of interest or pleasure
• Lower stomach cramps or pain
• Nausea
• Nervousness
• Nipple pain
• Normal menstrual bleeding occurring earlier, possibly lasting longer than expected
• Pain, redness, or swelling in the arm or leg
• Pain in the chest, groin, or legs, especially the calves
• Pain or discomfort in the arms, jaw, back, or neck
• Painful or tender cysts or lumps in the breasts
• Pelvic discomfort or pain
• Restlessness
• Shaking
• Slurred speech
• Stopping menstrual bleeding
• Sudden, severe weakness or numbness in the arm or leg
• Sudden loss of coordination
• Sweating
• Thoughts of killing oneself changes in behavior
• Tiredness
• Trouble breathing
• Trouble concentrating
• Trouble sleeping
• Unexpected or excess milk flow from the breasts
• Unusually heavy or unexpected menstrual bleeding
• Vaginal bleeding or spotting
• Vision changes
• Vomiting

Rare side effects of Estetrol-Drospirenone include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Estetrol-Drospirenone

• Tablet
  • 14.2 mg/3 mg

Contraception

Adult dosage

• Days 1-24: 1 active tablet (3 mg drospirenone [DRSP]/14.2 mg estetrol [E4]) orally once a day, THEN
• Days 25-28: 1 inert tablet orally once a day

Pediatric dosage

• A 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]) orally once a day, THEN
• Days 25-28: 1 inert tablet orally once a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

Drug Interactions 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• History of, increased risk for, or current arterial or venous thrombotic/thromboembolic diseases
• Examples include females with the following conditions
• Smoking, if aged above 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 (. g, subacute bacterial endocarditis with valvular disease, atrial fibrillation)

• Inherited or acquired hyper coagulopathies
• Uncontrolled hypertension or hypertension with vascular disease
• Diabetes mellitus with hypertension or end-organ damage; or diabetes mellitus of above 20 years duration
• Migraine headaches with aura
• Current or history of a hormonally sensitive malignancy (. g, 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

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Estetrol-Drospirenone?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Estetrol-Drospirenone?”

Cautions

• Increased blood pressure (BP) reported in females using COCs; the 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 the 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 the growth of any hormone receptor-positive tumor, both within and external to the female reproductive tract (.g, 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 the 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 an abdominal hemorrhage
• May decrease glucose tolerance; carefully monitor females with prediabetes and diabetes during therapy
• Females with hypertriglyceridemia or with a family history may have increased serum triglyceride concentrations during use, which may increase the 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 the association of COCs with the 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 the use of CHCs and the development of cervical cancer and intraepithelial neoplasia has not been established
• Exogenous estrogens may induce or exacerbate symptoms of hereditary angioedema; avoid them in females with hereditary angioedema
• Chloasma may occur with use, especially in females with a history of chloasma gravidarum; avoid in females with a history of chloasma gravidarum or increased sensitivity to the sun and/or ultraviolet radiation exposure
• Breast cancer
  • Epidemiology studies have not found a consistent association between the use of combined oral contraceptives (COCs) and breast cancer risk; studies do not show an association between every (current or past) use of COCs and the risk of breast cancer
  • Some studies report a small increase in the risk of breast cancer among current or recent users (below 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 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 tetracyclic) bleeding and spotting, especially during the 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 (.g, pregnancy, malignancy)
  • Females may also experience the absence of scheduled (withdrawal) bleeding, even if they are not pregnant; if scheduled bleeding does not occur, consider the possibility of pregnancy
  • If the patient has not adhered to the prescribed dosing schedule (missed 1 or 2 active tablets or started taking them a day later than prescribed), consider the possibility of pregnancy at the 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 hyper coagulopathy
  • Use of CHCs increases the risk of cardiovascular events and cerebrovascular events, (. g, myocardial infarction, stroke); risk is greater among females aged above 40, smokers, and females with hypertension, dyslipidemia, diabetes, or obesity; risk increases with age, particularly in females aged above 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) (. g, deep vein thrombosis, pulmonary embolism); the risk of VTE is highest during the first year of CHC use and when restarting hormonal contraception after a break above 4 weeks; risk of VTE returns to baseline approximately 3 months after CHC discontinued
• Postpartum VTE
  • VTE is increased during the first 6 weeks postpartum compared with the risk in nonpregnant, no postpartum 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 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 the first treatment cycle and monitored
  • Product contains drospirenone, a progestin, which has anti-mineralocorticoid activity, including the 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 an alternant contraceptive method (. g, 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 the 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 by prescribing information on corticosteroids and 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 a combination drug regimen of ombitasvir/paritaprevir/ritonavir (with or without dasabuvir)
    • May restart approximately 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 approximately 5 times ULN, including some cases above 20 times 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
    • The 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 and Lactation

• Discontinue if pregnancy occurs
• Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (. g, cardiac anomalies, limb-reduction defects) following COC exposure before conception or during early pregnancy
• 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 is 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 hours: resulting in a potential maximal daily dose below 1 mcg DRSP in an infant