Estradiol and dienogest

In the U.S.

• Natazia

Available Dosage Forms:

• Tablet

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about estradiol and dienogest, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about estradiol and dienogest. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using estradiol and dienogest.

Review Date: October 4, 2017

(es tra DYE ole & dye EN oh jest)

Contraception: Prevention of pregnancy.

Limitations of use: Efficacy has not been evaluated in women with a BMI >30 kg/m2.

Heavy menstrual bleeding: Treatment of heavy menstrual bleeding in women without organic pathology who choose to use an oral contraceptive as their method for contraception.

Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, combination oral contraceptives should not be used by women who are over 35 years of age and smoke.

Concerns related to adverse effects:

• Breast cancer: In women at risk for breast cancer due to family history or susceptibility genes (BRCA1, BRCA2), the use of combination hormonal contraceptives has not been shown to modify the risk for breast cancer. Breast cancer is a hormonal sensitive tumor and the prognosis for women with a current or recent history of breast cancer may be worse with combination hormonal contraceptive use (Curtis 2016b). Use is contraindicated in women with (or history of) breast cancer.

• Cervical cancer: The use of combination hormonal contraceptives has been associated with a slight increased risk of cervical cancer; however, studies are not consistent and may be related to additional risk factors (Gierisch 2013). Theoretically, use may affect prognosis of existing disease. Women awaiting treatment for cervical cancer may use combination hormonal contraceptives (Curtis 2016b).

• Chloasma: Combination hormonal contraceptives, as well as sun exposure and pregnancy, are triggers for chloasma. Women with a susceptibility to chloasma or additional risk factors should avoid exposure to sun or ultraviolet radiation during therapy (Handel 2014).

• Cholestasis: Risk of cholestasis may be increased with previous cholestatic jaundice of pregnancy or cholestasis with prior oral contraceptive use.

• Lipid effects: Combination hormonal contraceptives may adversely affect lipid levels, including serum triglycerides. Women with hypertriglyceridemia or a family history of hypertriglyceridemia may be at increased risk of pancreatitis when using combination hormonal contraceptives. Consider alternative contraception for women with uncontrolled dyslipidemia.

• Retinal vascular thrombosis: Discontinue if unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions occur and immediately evaluate for retinal vein thrombosis.

• Thromboembolic disorders: Discontinue use of combination hormonal contraceptives if an arterial or venous thrombotic event occurs. Oral contraceptives may increase the risk of venous thromboembolism (risk is greatest during first year of use and less than the risk observed with pregnancy); some studies suggest this risk may be higher in preparations with third- or fourth-generation progestins and/or high dose ethinyl estradiol. Women with inherited thrombophilias (eg, protein C or S deficiency, factor V Leiden mutation, prothrombin mutation, antithrombin deficiency) may have increased risk of venous thromboembolism. Age >35 years, hypertension, obesity, and tobacco use also increase the risk of thrombotic events in women taking combination hormonal contraceptives (ASRM 2017; Curtis 2016b; DeSancho 2010; van Vlijmen 2011). Combination hormonal contraceptives may also increase the risk of arterial thrombosis (eg, MI, stroke) and should not be used in women with a history of stroke or ischemic heart disease (Curtis 2016b). Use of combination hormonal contraceptives is contraindicated in women with a high risk of arterial or venous thrombotic disease.

• Vaginal bleeding: Breakthrough or intracyclic bleeding and spotting may occur, especially during the first 3 months of therapy. In addition, occasional missed periods may occur. Presentation of irregular, unresolving vaginal bleeding warrants further evaluation to rule out malignancy or pregnancy. Amenorrhea or oligomenorrhea may occur after discontinuing combination hormonal contraceptives, especially when such a condition was preexistent.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with risk factors for cardiovascular disease (eg, hypertension, low HDL, high LDL, high triglycerides, older age, diabetes, or women who smoke); use of combination hormonal contraceptives may increase the risk of cardiovascular disease (Curtis 2016b). Use is contraindicated in women at high risk of arterial or venous thrombotic diseases.

• Depression: Use with caution in patients with depression; discontinue if serious depression recurs.

• Diabetes: May impair glucose tolerance; use caution in women with diabetes or prediabetes. In general, use of combination oral contraceptives has limited effects on daily insulin needs and no long term effects on diabetes control in women with nonvascular disease. However, use in women with concomitant nephropathy, neuropathy, retinopathy, other vascular disease, or diabetes >20 years' duration should be evaluated for contraceptive use based on the severity of the condition (Curtis 2016b). Use is contraindicated in women with diabetes mellitus and vascular disease.

• Endometrial or ovarian cancer: The risk of endometrial or ovarian cancer is decreased in women using combination hormonal contraceptives (Curtis 2016b; Walker 2015). Oral contraceptives may be used to reduce the risk of ovarian cancer including those women with BRCA1 and BRCA2 mutations (Walker 2015). Women awaiting treatment for endometrial or ovarian cancer may use combination hormonal contraceptives (Curtis 2016b).

• Gallbladder disease: May cause an increased risk of gallbladder disease; may worsen existing gallbladder disease.

• Hepatic adenomas or carcinomas: Use of combination hormonal contraceptives is associated with hepatic adenomas (rare); fatal intra-abdominal hemorrhage may result. Risk is increased with long-term (>8 years) use. Use of this product is contraindicated in women with hepatic tumors.

• Hepatic impairment: Combination hormonal contraceptives may be poorly metabolized in women with hepatic impairment. Discontinue if jaundice develops during therapy or if liver function becomes abnormal. Use is contraindicated in women with hepatic disease. Use of combination hormonal contraceptives may be considered in women with mild (compensated) cirrhosis but should not be used in women with severe (decompensated) cirrhosis (Curtis 2016b).

• Hepatitis: Initiation of combination hormonal contraceptives is not recommended in women with acute viral hepatitis or during a flare. Continuation of use in women with chronic hepatitis has not been shown to increase the rate or severity of cirrhotic fibrosis or hepatocellular carcinoma. Continuation of use in women who are carriers has not been shown to trigger liver failure or severe hepatic dysfunction (Curtis 2016b).

• Hereditary angioedema: May induce or exacerbate symptoms of hereditary angioedema.

• Hypertension: The risk of hypertension may be increased with age, dose, and duration of use. Combination hormonal contraceptives should not be used in women with hypertension and vascular disease, or persistent blood pressure values ≥160 mm Hg systolic or ≥100 mm Hg diastolic. The risks of use may not outweigh the benefits of treatment in women with less severe hypertension (140 to 159 mm Hg systolic or 90 to 99 mm Hg diastolic) or those with hypertension that is adequately controlled (Curtis 2016a). Other risk factors for cardiovascular disease (eg, older age, smoking, diabetes) should be considered when prescribing contraceptives (Curtis 2016b). The manufacturer contraindicates use in women with uncontrolled hypertension.

• Migraine: Evaluate new, recurrent, severe or persistent headaches. Use of combination hormonal contraceptives may be considered in women who have migraines without aura (including menstrual migraines) (Curtis 2016b). Use in women with headaches with focal neurological symptoms, or migraine headaches with or without aura if >35 years is contraindicated.

• Solid organ transplant: Although data is limited, serious medical complications have been reported in women with complicated organ transplants (eg, graft failure, rejection, cardiac allograft vasculopathy); use of combination hormonal contraceptives is not recommended in women with complicated organ transplants (Curtis 2016b).

• Systemic lupus erythematosus: Women with systemic lupus erythematosus (SLE) are at an increased risk for heart disease, stroke, and VTE. Combination hormonal contraceptives should not be used in women with SLE who have positive (or unknown) antiphospholipid antibodies, due to an increased risk of arterial and venous thrombosis (Curtis 2016b).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Thyroid replacement therapy: Estrogens may increase thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels. Women on thyroid replacement therapy may require higher doses of thyroid hormone while receiving estrogens.

Special populations:

• Obese: This product has not been studied in women with a BMI >30 kg/m2. Available evidence suggests efficacy of combination hormonal contraceptives may be decreased in women with a BMI ≥30 kg/m2; however, reductions in effectiveness are considered minimal and information is conflicting. The risk of VTE may be increased in obese women using combination hormonal contraceptives. In general, the benefits of combination hormonal contraceptives may outweigh the risks in obese women who otherwise are eligible for this method (Curtis 2016b).

• Pediatric: Not for use prior to menarche.

• Postmenopausal women: Use is not indicated in postmenopausal women.

• Smokers: [US Boxed Warning]: Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives use. This risk increases with age, particularly in women over 35 years, and with the number of cigarettes smoked. For this reason, combination oral contraceptives should not be used by women who are over 35 years and smoke.

• Surgical patients: Whenever possible, should be discontinued at least 4 weeks prior to and for 2 weeks following elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.

Other warnings/precautions:

• HIV infection protection: Combination hormonal contraceptives do not protect against HIV infection or other sexually transmitted diseases (Curtis 2016a; Curtis 2016b).

• Laboratory changes: The use of estrogens and/or progestins may change the results of some laboratory tests (eg, coagulation factors, lipids, glucose tolerance, binding proteins).

Assessment of pregnancy status (prior to therapy); blood pressure (prior to therapy and yearly); weight (optional; BMI at baseline may be helpful to monitor changes during therapy); assess potential health status changes at routine visits (Curtis 2016a).

If all doses have not been taken on schedule and one menstrual period is missed, the possibility of pregnancy should be considered. If two consecutive menstrual periods are missed, assess pregnancy status before a new dosing cycle is started.

Monitor patient for vision changes; blood pressure; signs and symptoms of thromboembolic disorders; signs or symptoms of depression; glycemic control in patients with diabetes; lipid profiles in patients being treated for hyperlipidemias. Adequate diagnostic measures, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.