Taytulla

1 INDICATION S AND USAGE TAYTULLA is indicated for use by females of reproductive age to prevent pregnancy [ see Clinical Studies (14) ] . The efficacy of TAYTULLA in women with a body mass index (BMI) of more than 35 kg/m 2 has not been evaluated. TAYTULLA is a combination of norethindrone acetate, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy ( 1 ) The efficacy of TAYTULLA in females of reproductive potential with a body mass index (BMI) of > 35 kg/m 2 has not been evaluated ( 1 , 8.8 )

2 DOSAGE AND ADMINISTRATION Take one capsule by mouth at the same time every day ( 2.1 ) Take capsules in the order directed on the blister pack ( 2.1 ) Capsules may be administered without regard to meals ( 2.1 ) 2.1 How to Take TAYTULLA To achieve maximum contraceptive effectiveness, TAYTULLA must be taken exactly as directed. Instruct patients to take one capsule by mouth at the same time every day. Capsules must be taken in the order directed on the blister pack. Capsules should not be skipped or taken at intervals exceeding 24 hours. TAYTULLA may be administered without regard to meals [see Clinical Pharmacology (12.3) ] . 2.2 How to Start TAYTULLA Instruct the patient to begin taking TAYTULLA either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start). Day 1 Start During the first cycle of TAYTULLA use, instruct the patient to take one pink capsule daily, beginning on Day one (1) of her menstrual cycle (the first day of menstruation is Day one). She should take one pink capsule daily for 24 consecutive days, followed by one maroon capsule daily on days 25 through 28. TAYTULLA should be taken in the order directed on the package at the same time each day. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days if she starts taking TAYTULLA on a day other than the first day of her menstrual cycle. The possibility of ovulation and conception prior to initiation of medication should be considered. Sunday Start During the first cycle of TAYTULLA use, instruct the patient to take one pink capsule daily, beginning on the first Sunday after the onset of her menstrual period. She should take one pink capsule daily for 24 consecutive days, followed by one maroon capsule daily on days 25 through 28. TAYTULLA should be taken in the order directed on the package at the same time each day. TAYTULLA should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. The patient should begin her next and all subsequent 28-day regimens of TAYTULLA on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her pink capsules on the next day after ingestion of the last maroon capsule, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of TAYTULLA is started later than the day following administration of the last maroon capsule, the patient should use another method of contraception until she has taken a pink capsule daily for 7 consecutive days. For postpartum women who do not breastfeed or after a second trimester abortion, start TAYTULLA no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts TAYTULLA postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken TAYTULLA for 7 consecutive days. TAYTULLA may be initiated immediately after a first-trimester abortion or miscarriage; if the patient starts TAYTULLA immediately, additional contraceptive measures are not needed. Switching from another Hormonal Method of Contraception If the patient is switching from a combination hormonal method such as: • Another pill • Vaginal ring • Patch Instruct her to take the first pink capsule on the day she would have taken her next COC pill. She should not continue taking the tablet from her previous birth control pack and should not skip any days between packs. If she does not have a withdrawal bleed, rule out pregnancy before starting TAYTULLA. If she previously used a vaginal ring or transdermal patch, she should start using TAYTULLA on the day she would have resumed the previous product. If the patient is switching from a progestin-only method such as a: • Progestin-only pill • Implant • Intrauterine system • Injection She may switch any day from a progestin-only pill; instruct her to take the first pink capsule on the day she would have taken her next progestin-only pill. She should use a non-hormonal method of contraception for 7 consecutive days. If switching from an implant or injection, start the first pink capsule on the day her next injection would have been due or on the day of removal of her implant. If switching from an IUD, depending on the timing of removal, back-up contraception may be needed. 2.3 Missed Doses Table 1. Instructions for Missed TAYTULLA Capsules If one pink capsule is missed Take the missed capsule as soon as possible. Take the next capsule at the regular time. Continue taking one capsule a day until the pack is finished. Additional nonhormonal contraception (such as condoms) is not needed. If two pink capsules in a row are missed in Week 1 or Week 2 of the capsule pack Take the two missed capsules as soon as possible, and the next two capsules the next day. Continue taking one capsule a day until the pack is finished. Use additional nonhormonal contraception (such as condoms) until hormonal capsules have been taken for 7 days after missing capsules. If two pink capsules in a row are missed in Week 3 or Week 4 of the capsule pack Day 1 Starter: Throw out the rest of the TAYTULLA pack and start a new pack that same day. Sunday Starter: Keep taking one capsule every day until Sunday. On Sunday, throw out the rest of the pack and start a new pack of capsules that same day. Use additional nonhormonal contraception (such as condoms) until hormonal capsules have been taken for 7 days after missing capsules. If three or more pink capsules in a row are missed Day 1 Starter: Throw out the rest of the TAYTULLA pack and start a new pack that same day. Sunday Starter: Keep taking one capsule every day until Sunday. On Sunday, throw out the rest of the pack and start a new pack of capsules that same day. Bleeding may occur during the week following the missed capsules. Use additional nonhormonal contraception (such as condoms) until hormonal capsules have been taken for 7 days after missing capsules. If any of the four maroon capsules are missed Throw away the missed capsules. Continue taking the remaining capsules until the pack is finished. Additional nonhormonal contraception (such as condoms) is not needed. 2.4 Advice in Case of Gastrointestinal Disturbances If the patient vomits or has diarrhea (within 3 to 4 hours after she takes a pink capsule), she should follow the instructions in the “What to Do if You Miss Capsules” section [see Dosage and Administration ( 2.3 ) ] .

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) ] Adverse reactions commonly reported by COC users are: Irregular uterine bleeding Nausea Breast tenderness Headache The most common adverse reactions in clinical trials (≥ 2%) are headache, vaginal candidiasis, nausea, menstrual cramps, breast tenderness, bacterial vaginitis, abnormal cervical smear, acne, mood swings, and weight gain ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Relevant studies of risk of breast cancer with combined oral contraceptives 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data presented in Section 6.1 are from a clinical trial conducted with a 24-day regimen of norethindrone acetate 1 mg/ethinyl estradiol 0.020 mg tablets. TAYTULLA capsules are bioequivalent to these norethindrone acetate/ethinyl estradiol tablets. Common Adverse Reactions (≥ 2% of all Treated Subjects) : The most common adverse reactions reported by at least 2% of the 743 women using norethindrone acetate/ethinyl estradiol tablets were the following, in order of decreasing incidence: headache (6.3%), vaginal candidiasis (6.1%), nausea (4.6%), menstrual cramps (4.4%), breast tenderness (3.4%), bacterial vaginitis (3.1%), abnormal cervical smear (3.1%), acne (2.7%), mood swings (2.2%), and weight gain (2.0%). Adverse Reactions Leading to Study Discontinuation : Among the 743 women using norethindrone acetate/ethinyl estradiol tablets, 46 women (6.2%) withdrew because of an adverse event. Adverse events occurring in 3 or more subjects leading to discontinuation of treatment were, in decreasing order: abnormal or irregular bleeding (1.3%), nausea (0.8%), menstrual cramps (0.5%), and increased blood pressure (0.4%). 6.2 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 - 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 - 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 8-10 years of COC use. Figure 1. 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. The following adverse reactions have been identified during post approval use of a 24-day regimen of norethindrone acetate 1 mg/ethinyl estradiol 0.020 mg tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or evaluate a causal relationship to drug exposure. Vascular disorders: thrombosis/embolism (coronary artery, pulmonary, cerebral, deep vein). Hepatobiliary disorders: cholelithiasis, cholecystitis, hepatic adenoma, hemangioma of liver. Immune system disorders: hypersensitivity reaction. Skin and subcutaneous disorders: alopecia, rash (generalized and allergic), pruritus, skin discoloration. GI disorders: nausea, vomiting, abdominal pain. Musculoskeletal and connective tissue disorders: myalgia. Eye disorders: blurred vision, visual impairment, corneal thinning, change in corneal curvature (steepening). Infections and infestations: fungal infection, vaginal infection. Investigations: change in weight or appetite (increase or decrease), fatigue, malaise, peripheral edema, blood pressure increased. Nervous system disorders: headache, dizziness, migraine, loss of consciousness. Psychiatric disorders: mood swings, depression, insomnia, anxiety, suicidal ideation, panic attack, changes in libido. Renal and urinary disorders: cystitis-like syndrome. Reproductive system and breast disorders: breast changes (tenderness, pain, enlargement, and secretion), premenstrual syndrome, dysmenorrhea. Cardiovascular: chest pain, palpitations, tachycardia, myocardial infarction.

7 DRUG INTERACTIONS Consult the labeling of the concurrently-used drug to obtain further information about interactions with COCs or the potential for enzyme alterations. Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up method or alternative method of contraception when enzyme inducers are used with COCs ( 7.1 ) 7.1 Effects of Other Drugs on Combined Oral Contraceptives Substances diminishing the efficacy of COCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate and products containing St. John’s wort. Interactions between oral contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin and certain COCs containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone concentrations. Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma concentrations of estrogen and progestin have been noted in some cases of co-administration with HIV/HCV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors. Antibiotics: There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids. 7.2 Effects of Combined Oral Contraceptives on Other Drugs COCs containing ethinyl estradiol may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma concentrations of lamotrigine, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentration of thyroid-binding globulin increases with use of COCs. 7.3 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer TAYTULLA with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions (5.3) ]. 7.4 Interference with Laboratory Tests The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.

16.2 Storage Conditions Store at 25º C (77º F); excursions permitted to 15 to 30º C (59 to 86º F) [see USP Controlled Room Temperature].