TRI-LO-MARZIA

Product Type: HUMAN PRESCRIPTION DRUG

Route:

Dosage Form:

NDC: 63187-754

Application: ANDA200541

Effective: 20191101

1 INDICATIONS AND USAGE Tri-Lo-Marzia is an estrogen/progestin COC, indicated for use by women to prevent pregnancy. ( 1.1 ) 1.1 Oral Contraception Tri-Lo-Marzia™ 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 wallet. ( 2.2 ) • Do not skip or delay tablet intake. ( 2.2 ) 2.1 How to Start Tri-Lo-Marzia Tri-Lo-Marzia is dispensed in a wallet [see HOW SUPPLIED/STORAGE AND HANDLING ( 16 )]. Tri-Lo-Marzia 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 Tri-Lo-Marzia Table 1: Instructions for Administration of Tri-Lo-Marzia 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: Tri-Lo-Marzia active tablets are white to off white (Day 1 to Day 7), light blue (Day 8 to Day 15) and blue (Day 16 to Day 21) and 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 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 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 pack of Tri-Lo-Marzia. 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 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 Tri-Lo-Marzia from another oral contraceptive Start on the same day that a new pack of the previous oral contraceptive would have started. Switching from another contraceptive method to Tri-Lo-Marzia Start Tri-Lo-Marzia: 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 Tri-Lo-Marzia after Abortion or Miscarriage First-trimester: • After a first-trimester abortion or miscarriage, Tri-Lo-Marzia may be started immediately. An additional method of contraception is not needed if Tri-Lo-Marzia is started immediately. • If Tri-Lo-Marzia 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 Tri-Lo-Marzia. Second-trimester: • Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Tri-Lo-Marzia, 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 Tri-Lo-Marzia. [see CONTRAINDICATIONS ( 4 ), WARNINGS AND PRECAUTIONS ( 5.1 ), and FDA-APPROVED PATIENT LABELING.] Starting Tri-Lo-Marzia after Childbirth • Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Tri-Lo-Marzia following the instructions in Table 1 for women not currently using hormonal contraception. • Tri-Lo-Marzia 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 Tri-Lo-Marzia. [see CONTRAINDICATIONS ( 4 ), WARNINGS AND PRECAUTIONS ( 5.1 ), USE IN SPECIFIC POPULATIONS AND ( 8.1 AND 8.3 ), and FDA-APPROVED PATIENT LABELING]. Wallet Pack: SET THE DAY • Sunday Start: Each wallet has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen. • Day 1 Start: • Six different day label strips of the week have been provided with this pack in order to accommodate a Day-1 Start regimen. • Pick the day label strip that starts with the first day of your period. Place this day label strip over the area that has the days of the week (starting with Sunday) pre-printed on the wallet (Refer figure below). • Remove pill "1" by pushing down on the pill. The pill will come out through a hole in the back of the strip. • The patient should wait 24 hours to take the next pill. Continue to take one pill each day until all the pills have been taken. • When your wallet is empty, you will start a new wallet on the day after pill "28." The first pill in every refill will always be taken on the same day of the week, no matter when the patient's next period starts. wallet 2.3 Missed Tablets Table 2: Instructions for Missed Tri-Lo-Marzia 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 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 pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) should be used as backup 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 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 • A high risk of arterial or venous thrombotic diseases ( 4 ) • Liver tumors or liver disease ( 4 ) • Undiagnosed abnormal uterine bleeding ( 4 ) • Pregnancy ( 4 ) • Breast cancer or other estrogen- or progestin-sensitive cancer ( 4 ) Do not prescribe Tri-Lo-Marzia to women who are known to have 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 ( 5.3 )] o Have diabetes mellitus with vascular disease [see WARNINGS AND PRECAUTIONS ( 5.5 )] o Have headaches with focal neurological symptoms or migraine headaches with aura [see WARNINGS AND PRECAUTIONS ( 5.6 )] o Women over age 35 with any migraine headaches [see WARNINGS AND PRECAUTIONS ( 5.6 )] • Liver tumors, benign or malignant, or liver disease [see WARNINGS AND PRECAUTIONS ( 5.2 )] • Undiagnosed abnormal uterine bleeding [see WARNINGS AND PRECAUTIONS ( 5.7 )] • Pregnancy, because there is no reason to use COCs during pregnancy [see WARNINGS AND PRECAUTIONS ( 5.8 ) and USE IN SPECIFIC POPULATIONS ( 8.1 )] • Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past [see WARNINGS AND PRECAUTIONS ( 5.10 )]

Not available.

6 ADVERSE REACTIONS The most common adverse reactions reported during clinical trials (≥2%) were: headache/migraine, nausea/vomiting, breast issues, abdominal pain, menstrual disorders, mood disorders, acne, vulvovaginal infection, abdominal distension, weight increased, fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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 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 Tri-Lo-Marzia was evaluated in 1,723 subjects who participated in a randomized, partially blinded, multicenter, active-controlled clinical trial of Tri-Lo-Marzia for contraception. This trial examined healthy, nonpregnant, volunteers aged 18 to 45 (nonsmoker if 35 to 45 years of age), who were sexually active with regular coitus. Subjects were followed for up to 13 28-day cycles. Common Adverse Reactions (≥ 2% of subjects) The most common adverse reactions reported by at least 2% of the 1,723 women using the 28-day regimen were the following in order of decreasing incidence: headache/migraine (30.5%), nausea/vomiting (16.3%); breast issues (including tenderness, pain, enlargement, swelling, discharge, discomfort, cyst, and nipple pain) (10.3%), abdominal pain (9.2%), menstrual disorders (including dysmenorrhea, menstrual discomfort, menstrual disorder) (9.2%), mood disorders (including depression, mood altered, mood swings and depressed mood) (7.6%); acne (5.1%), vulvovaginal infection (3.5%), abdominal distension (2.8%), weight increased (2.4%), fatigue (2.1%). Adverse Reactions Leading to Study Discontinuation In the clinical trial of Tri-Lo-Marzia 4% of subjects discontinued the trial due to an adverse reaction. The most common adverse reactions leading to discontinuation were headache/migraine (1.2%), nausea/vomiting (0.7%), cervical dysplasia (0.7%), abdominal pain (0.4%), ovarian cyst (0.3%), acne (0.2%), flatulence (0.2%) and depression (0.2%). Serious Adverse Reactions Carcinoma of the cervix in situ (1 subject) and cervical dysplasia (1 subject). 6.2 Postmarketing Experience The following additional adverse drug reactions have been reported from worldwide postmarketing experience with norgestimate/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 (Including 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.