Nexesta Fe

1 INDICATIONS AND USAGE Nexesta Fe is indicated for use by females of reproductive potential to prevent pregnancy. Nexesta Fe is a progestin/estrogen COC indicated for use by females of reproductive potential to prevent pregnancy. ( 1 )

2 DOSAGE AND ADMINISTRATION Take one tablet by mouth at the same time every day. Tablets may be chewed or swallowed. ( 2.1 ) Take tablets in the order directed on the blister pack. ( 2.1 ) 2.1 How to Start Nexesta Fe Nexesta Fe is dispensed in a blister pack [see How Supplied/Storage and Handling (16) ] . Nexesta Fe may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration. 2.2 How to Take Nexesta Fe Nexesta Fe (white to off-white active tablets and brown placebo tablets) may be swallowed whole or chewed and swallowed. If the tablet is chewed, the patient should drink a full glass (8 ounces) of liquid immediately after swallowing. Table 1: Instructions for Administration of Nexesta Fe Starting CHCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start) Important: Consider the possibility of ovulation and conception prior to initiation of this product. Tablet Color: • Nexesta Fe active tablets are white to off-white (Day 1 to Day 21). • Nexesta Fe placebo tablets are brown (Day 22 to Day 28). Day 1 Start: • Take first white to off-white active tablet on the first day of menses. • Take subsequent white to off-white active tablets once daily at the same time each day for a total of 21 days. • Take one brown placebo tablet daily for 7 days and at the same time of day that active tablets were taken. • Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet). Sunday Start: • Take first active tablet on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient’s first cycle pack of Nexesta Fe. • Take subsequent white to off-white active tablets once daily at the same time each day for a total of 21 days. • Take one brown placebo tablet daily for the following 7 days and at the same time of day that active tablets were taken. • Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed. Switching to Nexesta Fe from another hormonal contraceptive Start on the same day that a new pack of the previous hormonal contraceptive would have started. Switching from another contraceptive method to Nexesta Fe Start Nexesta Fe: • Transdermal patch • On the day when next application would have been scheduled • Vaginal ring • On the day when next insertion would have been scheduled • Injection • On the day when next injection would have been scheduled • Intrauterine contraceptive • On the day of removal • If the IUD is not removed on first day of the patient’s menstrual cycle, additional non-hormonal contraceptive (such as condoms and spermicide) is needed for the first seven days of the first cycle pack. • Implant • On the day of removal Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling. Starting Nexesta Fe after Abortion or Miscarriage First-trimester After a first-trimester abortion or miscarriage, Nexesta Fe may be started immediately. An additional method of contraception is not needed if Nexesta Fe is started within 5 days after termination of the pregnancy. If Nexesta Fe is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of her first cycle pack of Nexesta Fe. Second-trimester Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Nexesta Fe, following the instructions in Table 1 for Day 1 or Sunday start, as desired. If using Sunday start, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient’s first cycle pack of Nexesta Fe. [See Contraindications (4) , Warnings and Precautions (5.1) , and FDA-Approved Patient Labeling .] Starting Nexesta Fe after Childbirth Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Nexesta Fe following the instructions in Table 1 for women not currently using hormonal contraception. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Nexesta Fe. [See Contraindications (4) , Warnings and Precautions (5.1) , Use in Specific Populations (8.1 and 8.3) , and FDA-Approved Patient Labeling ]. 2.3 Missed Tablets Table 2: Instructions for Missed Nexesta Fe Tablets If one white to off-white active tablet is missed in Weeks 1, 2, or 3 Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished. If two white to off-white active tablets are missed in Week 1 or Week 2 Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets. If two white to off-white active tablets are missed in Week 3 or three or more white to off-white active tablets are missed in a row in Weeks 1, 2, or 3 Day 1 start : Throw out the rest of the pack and start a new pack that same day. Sunday start : Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets. 2.4 Advice in Case of Gastrointestinal Disturbances In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling ] .

4 CONTRAINDICATIONS Nexesta Fe 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: o Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1) ] o Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1) ] o Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1) ] o Have cerebrovascular disease [see Warnings and Precautions (5.1) ] o Have coronary artery disease [see Warnings and Precautions (5.1) ] o Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions (5.1) ] o Have uncontrolled hypertension [see Warnings and Precautions (5.4) ] o Have diabetes mellitus with vascular disease [see Warnings and Precautions (5.6) ] o Have headaches with focal neurological symptoms or have migraine headaches with aura [see Warnings and Precautions (5.7) ] • Women over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] • Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions (5.2) ] • Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.8) ] • Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions (5.9) and Use in Specific Populations (8.1) ] • Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.11) ]. • Hypersensitivity to any of the components. • Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see Warnings and Precautions (5.3) ] A high risk of arterial or venous thrombotic diseases ( 4 ) Liver tumors or liver disease ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Pregnancy ( 4 ) Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir ( 4 )

Not available.

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 (5.2) ] The following adverse reactions are commonly reported by COC users. Because these reactions are voluntarily reported by from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Irregular uterine bleeding Nausea Breast tenderness Headache The most common adverse reactions were: irregular uterine bleeding, nausea, breast tenderness, and headache. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Postmarketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 to 1.12 (Figure 1). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1). One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 to 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8 to 10 years of COC use. Figure 1: Risk of Breast Cancer with Combined Oral Contraceptive Use RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs. Figure 1: Risk of Breast Cancer with Combined Oral Contraceptive Use