Norethindrone

INDICATIONS AND USAGE Hailey 1.5/30 is indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception. Oral contraceptives are highly effective. Table 1 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 methods can result in lower failure rates. TABLE 1 LOWEST EXPECTED AND TYPICAL FAILURE RATES DURING THE FIRST YEAR OF CONTINUOUS USE OF A METHOD % Of Women Experiencing an Unintended Pregnancy in the First Year of Continuous Use Method Lowest Expected* Typical** (No contraception) (85) (85) Oral contraceptives Combined progestin only 0.1 0.5 3 N/A*** N/A*** Diaphragm with spermicidal cream or jelly 6 20 Spermicides alone (foam, creams, gels, vaginal suppositories, and vaginal film) 6 26 Vaginal Sponge nulliparous parous 9 20 20 40 Implant 0.05 0.05 Injection: depot medroxyprogesterone acetate 0.3 0.3 IUD progesterone T copper T 380A LNg 20 1.5 0.6 0.1 2 0.8 0.1 Condom without spermicides female male 5 3 21 14 Cervical Cap with spermicidal cream or jelly nulliparous parous 9 26 20 40 Periodic abstinence (all methods) 1 to 9 25 Withdrawal 4 19 Female sterilization 0.5 0.5 Male sterilization 0.1 0.15 Adapted from RA Hatcher et al, Reference 7. *The authors' best guess of the percentage of women expected to experience an accidental pregnancy among couples who initiate a method (not necessarily for the first time) and who use it consistently and correctly during the first year if they do not stop for any other reason. **This term represents “typical” couples who initiate use of a method (not necessarily for the first time), who experience an accidental pregnancy during the first year if they do not stop use for any other reason. ***N/A-Data not available.

DOSAGE AND ADMINISTRATION The tablet dispenser has been designed to make oral contraceptive dosing as easy and as convenient as possible. The tablets are arranged in three rows of seven tablets each, with the days of the week appearing on the tablet dispenser above the first row of tablets. Note: Each tablet dispenser has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen. Six different day label strips have been provided with the Detailed Patient & Brief Summary Patient Package Insert in order to accommodate a Day-1 Start regimen. If the patient is using the Day-1 Start regimen, she should place the self-adhesive day label strip that corresponds to her starting day over the preprinted days. Important: The patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle when utilizing the Sunday-Start regimen. The possibility of ovulation and conception prior to initiation of use should be considered. Dosage and Administration for 21-Day Dosage Regimen To achieve maximum contraceptive effectiveness, Hailey 1.5/30 must be taken exactly as directed and at intervals not exceeding 24 hours. Hailey 1.5/30 provides the patient with a convenient tablet schedule of “3 weeks on-1 week off”. Two dosage regimens are described, one of which may be more convenient or suitable than the other for an individual patient. For the initial cycle of therapy, the patient begins her tablets according to the Day-1 Start or Sunday-Start regimen. With either regimen, the patient takes one tablet daily for 21 consecutive days followed by one week of no tablets. A. Sunday-Start Regimen: The patient begins taking tablets from the top row on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first tablet is taken on the same day. The last tablet in the dispenser will then be taken on a Saturday, followed by no tablets for a week (7 days). For all subsequent cycles, the patient then begins a new 21-tablet regimen on the eighth day, Sunday, after taking her last tablet. Following this regimen, of 21 days on-7 days off, the patient will start all subsequent cycles on a Sunday. B. Day-1 Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive day label strip that corresponds to her starting day over the preprinted days on the tablet dispenser. She starts taking one tablet daily, beginning with the first tablet in the top row. The patient completes her 21-tablet regimen when she has taken the last tablet in the tablet dispenser. She will then take no tablets for a week (7 days). For all subsequent cycles, the patient begins a new 21-tablet regimen on the eighth day after taking her last tablet, again starting with the first tablet in the top row after placing the appropriate day label strip over the preprinted days on the tablet dispenser. Following this regimen of 21 days on-7 days off, the patient will start all subsequent cycles on the same day of the week as the first course. Likewise, the interval of no tablets will always start on the same day of the week. Tablets should be taken regularly with a meal or at bedtime. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule. Special Notes on Administration Menstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after discontinuing medication. If spotting occurs while on the usual regimen of one tablet daily, the patient should continue medication without interruption. If the patient forgets to take one or more tablets, the following is suggested: One tablet is missed • take tablet as soon as remembered • take next tablet at the regular time Two consecutive tablets are missed (week 1 or week 2) • take two tablets as soon as remembered • take two tablets the next day • use another birth control method for seven days following the missed tablets Two consecutive tablets are missed (week 3) Sunday-Start Regimen: • take one tablet daily until Sunday • discard remaining tablets • start new pack of tablets immediately (Sunday) • use another birth control method for seven days following the missed tablets Day-1 Start Regimen: • discard remaining tablets • start new pack of tablets that same day • use another birth control method for seven days following the missed tablets Three (or more) consecutive tablets are missed Sunday-Start Regimen: • take one tablet daily until Sunday • discard remaining tablets • start new pack of tablets immediately (Sunday) • use another birth control method for seven days following the missed tablets Day-1 Start Regimen: • discard remaining tablets • start new pack of tablets that same day • use another birth control method for seven days following the missed tablets The possibility of ovulation occurring increases with each successive day that scheduled tablets are missed. While there is little l

ADVERSE REACTIONS An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section): • Thrombophlebitis • 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 to 1.12 (Figure 1) (70-74). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1) (70, 73, 75). 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: 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, although additional confirmatory studies are needed: • 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) • 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 • Budd-Chiari syndrome • Acne • Changes in libido • Colitis figure1