Tri Legest Fe Drug Information

The tablet dispenser has been designed to make Tri-Legest ® Fe (norethindrone acetate and ethinyl estradiol tablets, USP and ferrous fumarate tablets ) dosing as easy and as convenient as possible. The tablets are arranged in four 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 days of the week stickers 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 days of the week sticker 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 28-Day Dosage Regimen To achieve maximum contraceptive effectiveness, Tri-Legest ® Fe (norethindrone acetate and ethinyl estradiol tablets, USP and ferrous fumarate tablets ) should be taken exactly as directed and at intervals not exceeding 24 hours. Tri-Legest ® Fe (norethindrone acetate and ethinyl estradiol tablets, USP and ferrous fumarate tablets ) provides a continuous administration regimen consisting of 21 light pink, light yellow, and light blue tablets of norethindrone acetate and ethinyl estradiol and seven brown non-hormone containing tablets of ferrous fumarate.

The ferrous fumarate tablets are present to facilitate ease of drug administration via a 28-day regimen and do not serve any therapeutic purpose. There is no need for the patient to count days between cycles because there are no “off-tablet days”. A. Sunday-Start Regimen: The patient begins taking the first light pink tablet from the top row of the tablet dispenser (labeled Sunday) on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first light pink tablet is taken on the same day.

The patient takes one tablet daily for 21 days. The last light blue tablet in the dispenser will be taken on a Saturday. Upon completion of all 21 tablets, and without interruption, the patient takes one brown tablet daily for 7 days.

Upon completion of this first course of tablets, the patient begins a second course of 28-day tablets, without interruption, the next day (Sunday), starting with the Sunday light pink tablet in the top row. Adhering to this regimen of one tablet daily for 21 days, followed without interruption by one brown tablet daily for 7 days, the patient will start all subsequent cycles on a Sunday. B. Day-1 Start Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive days of the week sticker that corresponds to her starting day over the preprinted days on the tablet dispenser.

She starts taking one light pink tablet daily, beginning with the first light pink tablet in the top row. After the last light blue tablet (at the end of the third row) has been taken, the patient will then take the brown tablets for a week (7 days). For all subsequent cycles, the patient begins a new 28 tablet regimen on the eighth day after taking her last light blue tablet, again starting with the first tablet in the top row after placing the appropriate days of the week sticker over the preprinted days on the tablet dispenser. Following this regimen of 21 light pink, light yellow, and light blue tablets and 7 brown tablets, the patient will start all subsequent cycles on the same day of the week as the first course.

Tablets should be taken regularly at the same time each day and can be taken without regard to meals. 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 the brown tablets have been started.

In any event, the next course of tablets should be started without interruption. If spotting occurs while the patient is taking light pink, light yellow, or light blue tablets, continue medication without interruption. If the patient forgets to take one or more light pink, light yellow or light blue 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 light pink, light yellow and light blue tablets are missed.

While there is little likelihood of ovulation occurring if only one tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive light pink, light yellow, and light blue tablets are missed. If the patient forgets to take any of the seven brown tablets in week four, those brown tablets that were missed are discarded and one brown tablet is taken each day until the pack is empty.

A back-up birth control method is not required during this time. A new pack of tablets should be started no later than the eighth day after the last light blue tablet was taken. In the rare case of bleeding which resembles menstruation, the patient should be advised to discontinue medication and then begin taking tablets from a new tablet dispenser on the next Sunday or the first day (Day 1) depending on her regimen.

Persistent bleeding which is not controlled by this method indicates the need for reexamination of the patient, at which time nonfunctional causes should be considered. Use of Combined Oral Contraceptives in the Event of a Missed Menstrual Period 1. If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and combined oral contraceptives should be withheld until pregnancy has been ruled out. 2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen. After several months on treatment, bleeding may be reduced to a point of virtual absence.

This reduced flow may occur as a result of medication, in which event it is not indicative of pregnancy. Acne The timing of initiation of dosing with Tri-Legest ® Fe for acne should follow the guidelines for use of Tri-Legest ® Fe as a combined oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section for Tri-Legest ® Fe oral contraceptives.

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 4). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 4). 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 4: 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. An increased risk of the following serious adverse reactions has been associated with the use of combined 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 There is evidence of an association between the following conditions and the use of combined oral contraceptives, although additional confirmatory studies are needed: Mesenteric thrombosis Retinal thrombosis The following adverse reactions have been reported in patients receiving combined 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 Mood swings 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 combined 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 To report SUSPECTED ADVERSE EVENTS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions. 1

• 8. Drug Interactions Effects of Other Drugs on Combined Oral Contraceptives Rifampin: Metabolism of both norethindrone and ethinyl estradiol is increased by rifampin. A reduction in contraceptive effectiveness and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin.
• Anticonvulsants: Anticonvulsants such as phenobarbital, phenytoin, and carbamazepine, have been shown to increase the metabolism of ethinyl estradiol and/or norethindrone, which could result in a reduction in contraceptive effectiveness.
• Antibiotics: Pregnancy while taking combined oral contraceptives has been reported when the combined oral contraceptives were administered with antimicrobials such as ampicillin, tetracycline, and griseofulvin. However, clinical pharmacokinetic studies have not demonstrated any consistent effect of antibiotics (other than rifampin) on plasma concentrations of synthetic steroids.
• Atorvastatin: Coadministration of atorvastatin and an combined oral contraceptive increased AUC values for norethindrone and ethinyl estradiol by approximately 30% and 20%, respectively. St.
• John’s Wort: Herbal products containing St. John’s Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of combined oral contraceptives. This may also result in breakthrough bleeding. Human immunodeficiency virus (HIV)/Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors Significant changes (increase or decrease) in the plasma concentrations of estrogen and progestin have been noted in some cases of co-administration with HIV/HCV protease inhibitors (decrease or increase )/HCV protease inhibitors (decrease ) or with non-nucleoside reverse transcriptase inhibitors (decrease or increase ). Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation: Do not co-administer Tri-Legest ® Fe with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see WARNINGS, RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT ). Other: Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol concentrations, possibly by inhibition of conjugation. A reduction in contraceptive effectiveness and increased incidence of breakthrough bleeding has been suggested with phenylbutazone. Effects of Combined Oral Contraceptives on Other Drugs COCs containing ethinyl estradiol may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because the serum concentration of thyroid-binding globulin increase with use of COCs.

11. Pregnancy See CONTRAINDICATIONS and WARNINGS sections.

13. Pediatric Use Safety and efficacy of norethindrone acetate and ethinyl estradiol tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated.

Combined oral contraceptives should not be used in women who currently have the following: A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: Smoke, if over age 35 Have cerebrovascular disease Have coronary artery disease Have current or history of deep vein thrombosis or pulmonary embolism Have thrombogenic valvular or thrombogenic rhythm diseases of the heart Have inherited or acquired hypercoagulopathies Have uncontrolled hypertension or hypertension with vascular disease Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or with vascular disease or end-organ damage, or diabetes mellitus of > 20 years duration Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive 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 ).

Serious ill effects have not been reported following acute ingestion of large doses of combined oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females.