Estradiol valerate and Estradiol valerate/dienogest

• Natazia is a combination of dienogest, a progestin, and estradiol valerate, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. • The efficacy of Natazia in females of reproductive potential with a body mass index (BMI) of >30 kg/m 2 has not been evaluated. • Treatment of heavy menstrual bleeding in females of reproductive potential without organic pathology who choose to use an oral contraceptive as their method of contraception.

COCs lower the risk of becoming pregnant primarily by suppressing ovulation.

• Take one tablet daily by mouth at the same time every day. • Tablets must be taken in the order directed on the blister pack. • Do not skip or delay intake by more than 12 hours.

Natazia is contraindicated in females who are known to have or develop the following conditions: • A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: • Smoke, if over age 35 • Have deep vein thrombosis or pulmonary embolism, now or in the past • Have cerebrovascular disease • Have coronary artery disease • Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) • Have inherited or acquired hypercoagulopathies • Have uncontrolled hypertension • Have diabetes mellitus with vascular disease • Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 • Undiagnosed abnormal uterine bleeding • Current diagnosis of, or history of, breast cancer, which may be hormone sensitive • Liver tumors, benign or malignant, or liver disease )].

Boxed warning (cigarette smoking and serious cardiovascular events): Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs should not be used by women who are over 35 years of age and smoke. • Vascular risks: Stop Natazia if a thrombotic event occurs. Stop Natazia at least 4 weeks before and through 2 weeks after major surgery. Start Natazia no earlier than 4 weeks after delivery, in women who are not breastfeeding. • Liver disease: Discontinue Natazia if jaundice occurs. • High blood pressure: Do not prescribe Natazia for women with uncontrolled hypertension or hypertension with vascular disease.

The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: • Serious cardiovascular events and stroke • Vascular events • Liver disease Adverse reactions commonly reported by COC users are: • Irregular uterine bleeding • Nausea • Breast tenderness • Headache The most common adverse reactions (≥ 2%) in clinical trials for Natazia are headache (including migraines) 13%, breast pain 7%, menstrual disorders 7%, nausea/vomiting 6%, acne 4%, mood changes (3%) and increased weight 3%.

Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Drugs or herbal products that induce certain enzymes (for example, CYP3A4) may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs.

Storage Store at 25º C (77º F), excursions permitted to 15–30 o C (59–86 o F).