Estradiol Valerate And Estradiol Valerate/dienogest

1 INDICATIONS AND USAGE • Natazia is a combination of dienogest , a progestin, and estradiol valerate, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. ( 1 ) • The efficacy of Natazia in females of reproductive potential with a body mass index (BMI) of >30 kg/m 2 has not been evaluated. ( 1 , 8.8 ) • 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. ( 1.2 ) 1.1 Oral Contraception Natazia ® is indicated for use by women to prevent pregnancy. The efficacy of Natazia in women with a body mass index (BMI) of > 30 kg/m 2 has not been evaluated.

6 ADVERSE REACTIONS The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: • Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions ( 5.1 )] • Vascular events [see Warnings and Precautions ( 5.1 )] • Liver disease [see Warnings and Precautions ( 5.3 )] 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%. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc.

8.1 Pregnancy Risk Summary There is no reason to use COCs in pregnancy Discontinue Natazia if pregnancy occurs. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to COCs prior to conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.

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. 5 WARNINGS AND PRECAUTIONS • 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. ( 5.1 ) • Liver disease : Discontinue Natazia if jaundice occurs. ( 5.3 ) • High blood pressure : Do not prescribe Natazia for women with uncontrolled hypertension or hypertension with vascular disease. ( 5.4 ) • Carbohydrate and lipid metabolic effects : Monitor prediabetic and diabetic women taking Natazia. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. ( 5.6 ) • Headache : Evaluate significant change in headaches and discontinue Natazia if indicated. 4 CONTRAINDICATIONS Natazia is contraindicated in females who are known to have or develop the following conditions: • A high risk of arterial or venous thrombotic diseases.