Ethinyl estradiol and Segesterone

ANNOVERA is indicated for use by females of reproductive potential to prevent pregnancy. Limitations of Use ANNOVERA has not been adequately studied in females with a BMI >29 kg/m 2. ANNOVERA is a progestin/estrogen CHC indicated for use by females of reproductive potential to prevent pregnancy. Limitation of Usage Not adequately evaluated in females with a body mass index of >29 kg/m 2

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

One ANNOVERA is inserted in the vagina. The vaginal system must remain in place continuously for 3 weeks (21 days) followed by a 1-week (7 day) ring-free interval. One vaginal system provides contraception for thirteen 28-day cycles (1 year).

ANNOVERA 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 females who are known to: - Smoke, if over age 35. - Have current or history of deep vein thrombosis or pulmonary embolism. - 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 or hypertension with vascular disease. - Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or vascular disease, or other end-organ damage, or diabetes mellitus of >20 years duration. - Have headaches with focal neurological symptoms, migraine headaches with aura, or are over age 35 with any migraine headaches.

Boxed warning (cigarette smoking and serious cardiovascular events): Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive (CHC) use. This risk increases with age, particularly in females over 35 years of age, and with the number of cigarettes smoked. For this reason, CHC should not be used by females who are over 35 years of age and smoke. Thrombotic Disorders and Other Vascular Problems. Stop ANNOVERA if a thrombotic or thromboembolic event occurs. Stop ANNOVERA at least 4 weeks before and through 2 weeks after major surgery. Start ANNOVERA no earlier than 4 weeks after delivery, in females who are not breastfeeding. Consider cardiovascular risk factors before initiating in all females, particularly those over 35 years. Liver Disease: Discontinue if jaundice occurs.

The following adverse reactions are described elsewhere in other sections of the labeling: Serious cardiovascular events and stroke Vascular events Liver disease The most common adverse reactions (>5%) are headache/migraine, nausea/vomiting, vulvovaginal mycotic infection/candidiasis, abdominal pain lower/upper, dysmenorrhea, vaginal discharge, urinary tract infection, breast tenderness/pain/discomfort, bleeding irregularities including metrorrhagia, diarrhea, genital pruritus.

The sections below provide information on substances for which data on drug interactions with CHCs are available. There is little information available about the clinical effect of most drug interactions that may affect ANNOVERA. However, based on the known pharmacokinetic effects of these drugs, clinical strategies to minimize any potential adverse effect on contraceptive effectiveness or safety are suggested. Consult the approved product labeling of all concurrently used drugs to obtain further information about interactions with ANNOVERA or the potential for metabolic enzyme or transporter system alterations. Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of ANNOVERA or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with ANNOVERA.

Conditions Prior to dispensing ANNOVERA to the user, store ANNOVERA at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Do not refrigerate or freeze and avoid excessive heat.