desogestrel and ethinyl estradiol and ethinyl estradiol

INDICATIONS AND USAGE Desogestrel and Ethinyl Estradiol Tablets, USP and Ethinyl Estradiol Tablets, USP is indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Oral contraceptives are highly effective. Table II lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of these methods can result in lower failure rates. TABLE II: Percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of perfect use of contraception and the percentage continuing use at the end of the first year, United States. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year a Method (1) Typical Use b (2) Perfect Use c (3) (4) Chance d 85 85 Spermicides e 26 6 40 Periodic Abstinence 25 63 Calendar 9 Ovulation Method 3 Sympto-Thermal f 2 Post-Ovulation 1 Withdrawal 19 4 Cap g Parous Women 40 26 42 Nulliparous Women 20 9 56 Sponge Parous Women 40 20 42 Nulliparous Women 20 9 56 Diaphragm g 20 6 56 Condom h Female (Reality) 21 5 56 Male 14 3 61 Pill 5 71 Progestin Only 0.5 Combined 0.1 IUD Progesterone T 2 1.5 81 Copper T 380A 0.8 0.6 78 LNg 20 0.1 0.1 81 Depo-Provera 0.3 0.3 70 Norplant and Norplant-2 0.05 0.05 88 Female Sterilization 0.5 0.5 100 Male Sterilization 0.15 0.10 100 Adapted from Hatcher et al., 1998, ref #1. a) Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. b) Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. c) Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. d) The percents becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percent who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether. e) Foams, creams, gels, vaginal suppositories, and vaginal film. f) Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. g) With spermicidal cream or jelly. h) Without spermicides.

DOSAGE AND ADMINISTRATION To achieve maximum contraceptive effectiveness, maximum contraceptive effectiveness, desogestrel and ethinyl estradiol tablets and ethinyl estradiol tablets must be taken exactly as directed and at intervals not exceeding 24 hours. Desogestrel and ethinyl estradiol tablets and ethinyl estradiol tablets may be initiated using either a Sunday start or a Day 1 start. NOTE: Each blister is preprinted with the days of the week, starting with Sunday, to facilitate a Sunday start regimen. Six different "day label strips" are provided with each blister in order to accommodate a Day 1 start regimen. In this case, the patient should place the self-adhesive "day label strip" that corresponds to her starting day over the preprinted days. IMPORTANT: The possibility of ovulation and conception prior to initiation of use of desogestrel and ethinyl estradiol tablets and ethinyl estradiol tablets should be considered. The use of desogestrel and ethinyl estradiol tablets and ethinyl estradiol tablets for contraception may be initiated 4 weeks postpartum in women who elect not to breast-feed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (see CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS for Nursing mothers). If the patient starts on desogestrel and ethinyl estradiol tablets and ethinyl estradiol tablets postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a white to off-white tablet has been taken daily for 7 days. SUNDAY START When initiating a Sunday start regimen, another method of contraception should be used until after the first 7 consecutive days of administration. Using a Sunday start, tablets are taken daily without interruption as follows: The first white to off-white tablet should be taken on the first Sunday after menstruation begins (if menstruation begins on Sunday, the first white to off-white tablet is taken on that day). One white to off-white tablet is taken daily for 21 days, followed by 1 green (inert) tablet daily for 2 days and 1 light peach (active) tablet daily for 5 days. For all subsequent cycles, the patient then begins a new 28-tablet regimen on the next day (Sunday) after taking the last light peach tablet. [If switching from a Sunday start oral contraceptive, the first desogestrel and ethinyl estradiol tablets and ethinyl estradiol tablets should be taken on the second Sunday after the last tablet of a 21 day regimen or should be taken on the first Sunday after the last inactive tablet of a 28 day regimen.] If a patient misses 1 white to off-white tablet, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive white to off-white tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills. If the patient misses 2 consecutive white to off-white tablets in the third week or misses 3 or more white to off-white tablets in a row at any time during the cycle, the patient should keep taking 1 white to off-white tablet daily until the next Sunday. On Sunday the patient should throw out the rest of that cycle pack and start a new cycle pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills. DAY 1 START Counting the first day of menstruation as "Day 1", tablets are taken without interruption as follows: One white to off-white tablet daily for 21 days, one green (inert) tablet daily for 2 days followed by 1 light peach (ethinyl estradiol) tablet daily for 5 days. For all subsequ …

CONTRAINDICATIONS Oral contraceptives should not be used in women who currently have the following conditions: Thrombophlebitis or thromboembolic disorders A past history of deep vein thrombophlebitis or thromboembolic disorders Cerebral vascular or coronary artery disease Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia Undiagnosed abnormal genital bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Hepatic adenomas or carcinomas Known or suspected pregnancy Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ).

ADVERSE REACTIONS An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section): • Thrombophlebitis and venous thrombosis with or without embolism • Arterial thromboembolism • Pulmonary embolism • Myocardial infarction • Cerebral hemorrhage • Cerebral thrombosis • Hypertension • Gallbladder disease • Hepatic adenomas or benign liver tumors 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) (64-68). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2) (64, 67, 69). 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: RELEVANT STUDIES OF RISK OF BREAST CANCER WITH COMBINED ORAL CONTRACEPTIVES 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. There is evidence of an association between the following conditions and the use of oral contraceptives: • Mesenteric thrombosis • Retinal thrombosis The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: • Nausea • Vomiting • Gastrointestinal symptoms (such as abdominal cramps and bloating) • Breakthrough bleeding • Spotting • Change in menstrual flow • Amenorrhea • Temporary infertility after discontinuation of treatment • Edema • Melasma which may persist • Breast changes: tenderness, enlargement, secretion • Change in weight (increase or decrease) • Change in cervical erosion and secretion • Diminution in lactation when given immediately postpartum • Cholestatic jaundice • Migraine • Rash (allergic) • Mental depression • Reduced tolerance to carbohydrates • Vaginal candidiasis • Change in corneal curvature (steepening) • Intolerance to contact lenses The following adverse reactions have been reported in users of oral contraceptives and the association has been neither confirmed nor refuted: • Pre-menstrual syndrome • Cataracts • Changes in appetite • Cystitis-like syndrome • Headache • Nervousness • Dizziness • Hirsutism • Loss of scalp hair • Erythema multiforme • Erythema nodosum • Hemorrhagic eruption • Vaginitis • Porphyria • Impaired renal function • Hemolytic uremic syndrome • Acne • Changes in libido • Colitis Budd-Chiari Syndrome FIGURE 2: RELEVANT STUDIES OF RISK OF BREAST CANCER WITH COMBINED ORAL CONTRACEPTIVES

DESCRIPTION Desogestrel and Ethinyl Estradiol Tablets, USP and Ethinyl Estradiol Tablets, USP provide an oral contraceptive regimen of 21 white to off white round tablets each containing 0.15 mg desogestrel (13-ethyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol), 0.02 mg ethinyl estradiol (19-nor-17 alpha-pregna-1,3,5 (10)-trien-20-yne-3,17-diol), and inactive ingredients which include lactose monohydrate, pregelatinized starch (Maize starch), povidone K-30, vitamin E, stearic acid, colloidal anhydrous silica, purified talc, magnesium stearate, Hypromellose, Polyethylene glycol and followed by 2 inert light-green round tablets with the following inactive ingredients /lactose monohydrate, pregelatinized starch (Starch 1500), colloidal anhydrous silica, talc, magnesium stearate, hypromellose, triacetin, titanium dioxide, FD&C blue no. 1 aluminium lake, D&C yellow no. 10 aluminium lake, FD&C yellow no. 6 aluminium lake. Desogestrel and Ethinyl Estradiol Tablets, USP and Ethinyl Estradiol Tablets, USP also contains 5 yellow coloured round tablets containing 0.01 mg ethinyl estradiol (19-nor-17 alpha-pregna-1,3,5 (10)-trien-20-yne-3,17-diol) and inactive ingredients which include lactose monohydrate, pregelatinized starch (Maize starch), povidone K-30, vitamin E, stearic acid, colloidal anhydrous silica, purified talc, hypromellose, polyethylene glycol, polysorbate 80, titanium dioxide, D&C yellow no. 10 aluminium lake, FD&C yellow no. 6 aluminium lake. The molecular weights for desogestrel and ethinyl estradiol are 310.48 and 296.40 respectively. The structural formulas are as follows: image description

OVERDOSAGE Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females. NON-CONTRACEPTIVE HEALTH BENEFITS The following non-contraceptive health benefits related to the use of oral contraceptives are supported by epidemiologic studies which largely utilized oral contraceptive formulations containing estrogen doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol (73–78). Effects on menses: • increased menstrual cycle regularity • decreased blood loss and decreased incidence of iron deficiency anemia • decreased incidence of dysmenorrhea Effects related to inhibition of ovulation: • decreased incidence of functional ovarian cysts • decreased incidence of ectopic pregnancies Effects from long-term use: • decreased incidence of fibroadenomas and fibrocystic disease of the breast • decreased incidence of acute pelvic inflammatory disease • decreased incidence of endometrial cancer decreased incidence of ovarian cancer

HOW SUPPLIED Desogestrel and Ethinyl Estradiol Tablets, USP and Ethinyl Estradiol Tablets, USP are available in 28 days regimen of blister pack (NDC 79929-020-05) as follows: 21 White to off white, round, biconvex, film coated tablets, debossed with FT1 on one side and plain on other side containing 0.15 mg desogestrel and 0.02 mg ethinyl estradiol, 2 light-green coloured, round, biconvex, film coated tablets debossed with FT3 on one side and plain on other side containing inert ingredients and 5 Yellow coloured, round, biconvex, film coated tablets, debossed with FT2 on one side and plain on other side containing 0.01 mg ethinyl estradiol. Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. The blister packs are available in boxes of 3.