Estarylla

Product Type: HUMAN PRESCRIPTION DRUG

Route:

Dosage Form:

NDC: 70700-119

Application: ANDA090794

Effective: 20230201

1 INDICATIONS AND USAGE Estarylla (norgestimate and ethinyl estradiol tablets, USP),are an estrogen/progestin COCs, indicated for use by women to prevent pregnancy. ( 1.1 ) 1.1 Oral Contraceptive Estarylla (norgestimate and ethinyl estradiol tablets) are indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14) ] .

2 DOSAGE AND ADMINISTRATION • Take one tablet daily by mouth at the same time every day. ( 2.2 ) • Take tablets in the order directed on the blister pack. ( 2.2 ) • Do not skip or delay tablet intake. ( 2.2 ) 2.1 How to Start Estarylla? Estarylla (norgestimate and ethinyl estradiol tablets), dispensed in a blister pack [see HOW SUPPLIED/STORAGE AND HANDLING ( 16 )]. Estarylla 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 Estarylla? Table 1: Instructions for Administration of Estarylla Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling. Starting COCs 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: • Estarylla active tablets are blue (Day 1 to Day 21). • Estarylla has green inactive tablets (Day 22 to Day 28) Day 1 Start: • Take first active tablet without regard to meals on the first day of menses. • Take subsequent active tablets once daily at the same time each day for a total of 21 days. • Take one green inactive tablet daily for 7 days and at the same time of day that active tablets were taken. • Begin each subsequent blister pack on the same day of Estarylla™ the week as the first cycle blister pack (i.e., on the day after taking the last inactive tablet) Sunday Start: • Take first active tablet without regard to meals 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 blister pack of Estarylla . • Take subsequent active tablets once daily at the same time each day for a total of 21 days. • Take one green inactive tablet daily for the following 7 days and at the same time of day that active tablets were taken. • Begin each subsequent blister pack on the same day of the week as the first cycle blister pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed. Switching to Estarylla from another oral contraceptive Start on the same day that a new blister pack of the previous oral contraceptive would have started. Switching from another contraceptive method to Estarylla Start Estarylla : • 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 blister pack. • Implant • On the day of removal Starting Estarylla after Abortion or Miscarriage First-trimester • After a first-trimester abortion or miscarriage, Estarylla may be started immediately. An additional method of contraception is not needed if Estarylla is started immediately. • If Estarylla 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 blister pack of Estarylla. Second-trimester • Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Estarylla, 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 blister pack of Estarylla [see CONTRAINDICATIONS (4) , WARNINGS AND PRECAUTIONS (5.1) , and FDA-APPROVED PATIENT LABELING ]. Starting Estarylla after Childbirth • Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Estarylla following the instructions in Table 1 for women not currently using hormonal contraception. • Estarylla is not recommended for use in lactating women [see USE IN SPECIFIC POPULATIONS (8.3) ]. • If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Estarylla. [See CONTRAINDICATIONS (4) , WARNINGS AND PRECAUTIONS (5.1) , USE IN SPECIFIC POPULATIONS (8.1 and 8.3) , and FDA-Approved Patient Labeling ]. BEFORE YOU START TAKING YOUR PILLS • DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take it at about the same time every day. • LOOK AT YOUR PILL PACK The pill blister pack has 21 active pills (with hormones) to take for 3 weeks. This is followed by 1 week of reminder green pills (without hormones). There are 21 blue active pills, and 7 green reminder pills. 3. ALSO FIND: 1. where on the blister pack to start taking pills, 2. in what order to take the pills (follow the arrows) 3. The week numbers as shown in the diagram below. 4 BE SURE YOU HAVE READY AT ALL TIMES: Another kind of birth control (such as a condom or spermicide) to use as a back-up method in case you miss pills. An extra, full pill blister pack. 2.3 Missed Tablets Table 2: Instructions for Missed Estarylla Tablets If one 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 blister pack is finished. If two 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 blister 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 active tablets are missed in the third week or three or more active tablets are missed in a row in Weeks 1, 2, or 3 Day 1 start: Throw out the rest of the blister 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 blister pack and start a new blister 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 Estarylla 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 [see BOXED WARNING and WARNINGS AND PRECAUTIONS ( 5.1 )] • Have deep vein thrombosis or pulmonary embolism, now or in the past [see WARNINGS AND PRECAUTIONS ( 5.1 )] • Have inherited or acquired hypercoagulopathies [see WARNINGS AND PRECAUTIONS ( 5.1 )] • Have cerebrovascular disease [see WARNINGS AND PRECAUTIONS ( 5.1 )] • Have coronary artery disease [see WARNINGS AND PRECAUTIONS ( 5.1 )] • 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)] • Have uncontrolled hypertension [see WARNINGS AND PRECAUTIONS ( 5.4 )] • Have diabetes mellitus with vascular disease [see WARNINGS AND PRECAUTIONS ( 5.6 )] • Have headaches with focal neurological symptoms or 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 (5.8) 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 )] 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 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 reported during clinical trials (≥2%) were: Norgestimate and ethinyl estradiol: headache/migraine, abdominal/gastrointestinal pain, vaginal infection, genital discharge, breast issues (including breast pain, discharge, and enlargement), mood disorders (including depression and mood altered), flatulence, nervousness, rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Xiromed, LLC. at 1-844-XIROMED (844-947-6633) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of norgestimate and ethinyl estradiol was evaluated in 1,647 healthy women of child-bearing potential who participated in 3 clinical trials and received at least 1 dose of norgestimate and ethinyl estradiol for contraception. Two trials were randomized active-controlled trials and 1 was an uncontrolled open-label trial. In all 3 trials, subjects were followed for up to 24 cycles. Common Adverse Reactions (≥ 2% of subjects): The most common adverse reactions reported by at least 2% of the 1,647 women were the following in order of decreasing incidence: headache/migraine (32.9%), abdominal/gastrointestinal pain (7.8%), vaginal infection (8.4%), genital discharge (6.8%), breast issues (including breast pain, discharge, and enlargement) (6.3%), mood disorders (including depression and mood altered) (5%), flatulence (3.2%), nervousness (2.9%), and rash (2.6%). Adverse Reactions Leading to Study Discontinuation: Over the three trials, between 11 to 21% of subjects discontinued the trial due to an adverse reaction. The most common adverse reactions (≥1%) leading to discontinuation were: metrorrhagia (6.9%), nausea/vomiting (5%), headache (4.1%), mood disorders (including depression and mood altered) (2.4%), premenstrual syndrome (1.7%), hypertension (1.4%), breast pain (1.4%), nervousness (1.3%), amenorrhea (1.1%), dysmenorrhea (1.1%), weight increased (1.1%), and flatulence (1.1%). Serious Adverse Reactions: breast cancer (1 subject), mood disorders including depression, irritability, and mood swings (1 subject), myocardial infarction (1 subject), and venous thromboembolic events including pulmonary embolism (1 subject) and deep vein thrombosis (DVT) (1 subject). 6.2 Postmarketing Experience Post Marketing 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 2). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). 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 2: 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. The following additional adverse drug reactions have been reported from worldwide postmarketing experience with norgestimate and ethinyl estradiol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infections and Infestations : Urinary tract infection; Neoplasms Benign, Malignant and Unspecified (Incl. Cysts and Polyps) : Breast cancer, benign breast neoplasm, hepatic adenoma, focal nodular hyperplasia, breast cyst; Immune System Disorders : Hypersensitivity; Metabolism and Nutrition Disorders : Dyslipidemia; Psychiatric Disorders : Anxiety, insomnia; Nervous System Disorders : Syncope, convulsion, paresthesia, dizziness; Eye Disorders : Visual impairment, dry eye, contact lens intolerance; Ear and Labyrinth Disorders : Vertigo; Cardiac Disorders : Tachycardia, palpitations; Vascular Events : Deep vein thrombosis, pulmonary embolism, retinal vascular thrombosis, hot flush; Arterial Events: Arterial thromboembolism, myocardial infarction, cerebrovascular accident; Respiratory, Thoracic and Mediastinal Disorders : Dyspnea; Gastrointestinal Disorders : Pancreatitis, abdominal distension, diarrhea, constipation; Hepatobiliary Disorders : Hepatitis; Skin and Subcutaneous Tissue Disorders : Angioedema, erythema nodosum, hirsutism, night sweats, hyperhidrosis, photosensitivity reaction, urticaria, pruritus, acne; Musculoskeletal, Connective Tissue, and Bone Disorders : Muscle spasms, pain in extremity, myalgia, back pain; Reproductive System and Breast Disorders : Ovarian cyst, suppressed lactation, vulvovaginal dryness; General Disorders and Administration Site Conditions : Chest pain, asthenic conditions.