Melodetta 24 Fe

Product Type: HUMAN PRESCRIPTION DRUG

Route:

Dosage Form:

NDC: 69238-1031

Application: ANDA207514

Effective: 20230629

1 INDICATIONS AND USAGE Melodetta™ 24 Fe is indicated for use by females of reproductive age to prevent pregnancy [see Clinical Studies (14) ] . The efficacy of Melodetta 24 Fe in women with a body mass index (BMI) of more than 35 kg/m 2 has not been evaluated. Melodetta™ 24 Fe is an estrogen/progestin COC indicated for use by women to prevent pregnancy (1) The efficacy in women with a body mass index of more than 35 kg/m 2 has not been evaluated (1, 8.8)

2 DOSAGE AND ADMINISTRATION One tablet daily chewed and swallowed or swallowed whole taken at the same time of day. Follow with 8 ounces of water (2.1) Take one tablet by mouth at the same time every day for 28 days (2.1) Take tablets in the order directed on the blister pack (2.1) Tablets may be administered without regard to meals (12.3) 2.1 How to Take Melodetta 24 Fe To achieve maximum contraceptive effectiveness, Melodetta 24 Fe must be taken exactly as directed. Instruct patients to take one tablet by mouth at the same time every day. The tablet may be chewed and swallowed or swallowed whole. The patient should drink a full glass (8 ounces) of water immediately after the white tablets are chewed or swallowed whole. Tablets must be taken in the order directed on the blister pack. Tablets should not be skipped or taken at intervals exceeding 24 hours. For patient instructions for missed tablets, [see FDA-approved patient labeling ] . Melodetta 24 Fe may be administered without regard to meals [see Clinical Pharmacology (12.3) ] . 2.2 How to Start Melodetta 24 Fe Instruct the patient to begin taking Melodetta 24 Fe 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 Melodetta 24 Fe use, instruct the patient to take one white Melodetta 24 Fe tablet daily, beginning on Day one (1) of her menstrual cycle (the first day of menstruation is Day one). She should take one white Melodetta 24 Fe tablet daily for 24 consecutive days, followed by one brown ferrous fumarate tablet daily on days 25 through 28. Melodetta 24 Fe 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 Melodetta 24 Fe 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 Melodetta 24 Fe use, instruct the patient to take one white Melodetta 24 Fe tablet daily, beginning on the first Sunday after the onset of her menstrual period. She should take one white Melodetta 24 Fe tablet daily for 24 consecutive days, followed by one brown ferrous fumarate tablet daily on days 25 through 28. Melodetta 24 Fe should be taken in the order directed on the package at the same time each day. Melodetta 24 Fe 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 Melodetta 24 Fe on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her white Melodetta 24 Fe tablets on the next day after ingestion of the last brown tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Melodetta 24 Fe is started later than the day following administration of the last brown ferrous fumarate tablet, the patient should use another method of contraception until she has taken a white Melodetta 24 Fe tablet daily for 7 consecutive days. For postpartum women who do not breastfeed or after a second trimester abortion, start Melodetta 24 Fe no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts on Melodetta 24 Fe 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 Melodetta 24 Fe for 7 consecutive days. Melodetta 24 Fe may be initiated immediately after a first-trimester abortion or miscarriage; if the patient starts Melodetta 24 Fe immediately, additional contraceptive measures are not needed. 2.3 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 white Melodetta 24 Fe tablet on the day she would have taken her next COC pill. She should not continue taking the tablets 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 Melodetta 24 Fe. If she previously used a vaginal ring or transdermal patch, she should start using Melodetta 24 Fe 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 white Melodetta 24 Fe tablet 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 white Melodetta 24 Fe tablet 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. 2.4 Advice in Case of Gastrointestinal Disturbances If the patient vomits or has diarrhea (within 3 to 4 hours after she takes a white Melodetta 24 Fe tablet), she should follow the instructions in the “ What to Do if You Miss Tablets ” section [see FDA-approved patient labeling ] .

4 CONTRAINDICATIONS Melodetta 24 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: 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 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 inherited or acquired hypercoagulopathies [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 (5.5) ] Have headaches with focal neurological symptoms or have migraine headaches with aura All women over age 35 with migraine headache [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) ] Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.10) ] 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) Breast cancer (4) Liver tumors or liver disease (4) Undiagnosed abnormal uterine bleeding (4) Pregnancy (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) ] Adverse reactions commonly reported by COC users are: Irregular uterine bleeding Nausea Breast tenderness Headache The most common adverse reactions in clinical trials (greater than or equal to 2%) were: 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 Amneal Pharmaceuticals at 1-877-835-5472 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 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. Melodetta 24 Fe is bioequivalent to these norethindrone acetate/ethinyl estradiol tablets. Common Adverse Reactions (Greater Than or Equal to 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%). 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 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 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. 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. Adverse reactions are grouped into System Organ Classes. 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. 1