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Norethindrone, Ethinyl Estradiol, And Ferrous Fumarate

FDA Drug Information • Also known as: Layolis Fe

Brand Names
Layolis Fe
Route
ORAL
Dosage Form
KIT
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs should not be used by women who are over 35 years of age and smoke [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 ) ]. WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS See full prescribing information for complete boxed warning. Women over 35 years old who smoke should not use LAYOLIS Fe. ( 4 ) Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. ( 4 )

Description

11 DESCRIPTION LAYOLIS Fe provides an oral contraceptive regimen consisting of 24 tablets that contain the active ingredients specified below, followed by four non-hormonal placebo tablets: 24 light green, round tablets each containing 0.8 mg norethindrone and 0.025 mg ethinyl estradiol 4 brown, round tablets each containing 75 mg ferrous fumarate Each light green tablet also contains the following inactive ingredients: D&C Yellow No. 10 aluminum lake, FD&C Blue No. 1 aluminum lake, FD&C Yellow No. 6 aluminum lake, lactose monohydrate, magnesium stearate, mannitol, microcrystalline cellulose, povidone, sodium starch glycolate, spearmint flavor, sucralose and vitamin E. Each brown, round tablet contains ferrous fumarate, magnesium stearate, mannitol, microcrystalline cellulose, povidone, sodium starch glycolate, spearmint flavor and sucralose. The ferrous fumarate chewable tablets do not serve any therapeutic purpose. Ferrous fumarate chewable tablets are not USP for dissolution and assay. The empirical formula of ethinyl estradiol is C 20 H 24 O 2 and the chemical structure is: The chemical name of ethinyl estradiol is [19-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol,(17α)-] The empirical formula of norethindrone is C 20 H 26 O 2 and the chemical structure is: The chemical name of norethindrone is [17-hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one] Chemical structure of ethinyl estradiol. Chemical structure for norethindrone.

What Is Norethindrone, Ethinyl Estradiol, And Ferrous Fumarate Used For?

1 INDICATIONS AND USAGE LAYOLIS Fe is indicated for use by women to prevent pregnancy. The efficacy of LAYOLIS Fe in women with a body mass index (BMI) of > 35 kg/m 2 has not been evaluated. LAYOLIS Fe is a combination of norethindrone, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. ( 1 ) The efficacy in females of reproductive potential with a body mass index (BMI) of > 35 kg/m 2 has not been evaluated. ( 1 , 8.8 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Chew one tablet without water at the same time every day. ( 2.1 ) Take tablets in the order directed on the blister pack. ( 2.1 ) 2.1 How to Take LAYOLIS Fe To achieve maximum contraceptive effectiveness, LAYOLIS Fe must be taken exactly as directed. Chew and swallow one tablet without water at the same time every day. Tablets must be taken in the order directed on the blister pack. Tablets should not be skipped or taken at intervals exceeding 24 hours. LAYOLIS Fe may be administered without regard to meals [see Clinical Pharmacology ( 12.3 )] . 2.2 How to Start LAYOLIS Fe Instruct the patient to begin taking LAYOLIS Fe on Day 1 of her menstrual cycle (that is, the first day of her menstrual bleeding). One light green tablet should be taken daily for 24 consecutive days followed by one brown tablet daily for 4 consecutive days . Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days if she starts taking LAYOLIS Fe other than on the first day of her menstrual cycle. For postpartum women who do not breastfeed or after a second trimester abortion, LAYOLIS Fe may be started no earlier than 4 weeks postpartum. Recommend use of a non-hormonal back-up method for the first 7 days. When combined oral contraceptives (COCs) are used during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. The possibility of ovulation and conception before starting COCs should also be considered. If the patient is switching from a combination hormonal method such as: - Another pill - Vaginal ring - Patch Instruct her to take the first light green pill on the day she would have started a new cycle of her previous birth control pack (Day 1). If she previously used a vaginal ring or transdermal patch, she should start using LAYOLIS Fe on the day she would have restarted the ring or patch. Instruct the patient to use a non-hormonal back-up method such as a condom and spermicide for the first 7 days. If the patient is switching from a progestin-only method such as: - Progestin-only pill - Implant - Intrauterine system - Injection Instruct her to take the first light green pill on the day she would have taken her next progestin-only pill or on the day of removal of her implant or intrauterine system or on the day when she would have had her next injection. Instruct the patient to use a non-hormonal back-up method such as a condom and spermicide for the first 7 days. 2.3 Missed Doses Table 1. Instructions for Missed LAYOLIS Fe Tablets If one light green tablet is missed Take the missed tablet as soon as possible. Take the next tablet at the regular time. Continue taking one tablet a day until the pack is finished. Additional nonhormonal contraception (such as condoms) is not needed. If two light green tablets in a row are missed in Week 1 or Week 2 of the tablet pack Take the two missed tablets as soon as possible, and the next two tablets...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: Serious cardiovascular events and smoking [see Boxed Warning , and Warnings and Precautions ( 5.1 )] Vascular events [see Warnings and Precautions ( 5.1 )] Liver disease [see Warnings and Precautions ( 5.3 )] Adverse reactions commonly reported by COC users are: Irregular uterine bleeding Nausea Breast tenderness Headache The most common adverse reactions (≥ 2%) are nausea/vomiting (8.8%), headaches/migraine (7.5%), depression/mood complaints (4.1%), dysmenorrhea (3.9%), acne (3.2%), anxiety symptoms (2.4%), breast pain/tenderness (2.4%), and increased weight (2.3%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-888-838-2872 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 rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A phase 3 clinical trial evaluated the safety and efficacy of LAYOLIS Fe for pregnancy prevention. The study was a multicenter, non-comparative, open-label study with a treatment duration of 12 months (thirteen 28-day cycles). A total of 1,677 women aged 18-46 were enrolled and took at least one dose of LAYOLIS Fe. Adverse Reactions Leading to Study Discontinuation: 8.5% of the women discontinued from the clinical trial due to an adverse reaction. The most common adverse reactions leading to discontinuation were nausea (1.0%), weight increase (0.8%), acne (0.8%), metrorrhagia (0.7%), altered mood (0.4%), hypertension (0.4%), irritability (0.3%), migraine (0.3%), decreased libido (0.3%) and mood swings (0.3%). Common Adverse Reactions (≥ 2% of all treated subjects): nausea/vomiting (8.8%), headaches/migraine (7.5%), depression/mood complaints (4.1%), dysmenorrhea (3.9%), acne (3.2%), anxiety symptoms (2.4%), breast pain/tenderness (2.4%), and increased weight (2.3%). Serious Adverse Reactions: Hypertension, depression, cholecystitis, and deep vein thrombosis. 6. 2 Postmarketing 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 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 - 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 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. Figure 1

Drug Interactions

7 DRUG INTERACTIONS No drug-drug interaction studies were conducted with LAYOLIS Fe. Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up method or alternative method of contraception when enzyme inducers are used with COCs. ( 7.1 ) 7.1 Changes in Contraceptive Effectiveness Associated with Co-Administration of Other Products If a woman on hormonal contraceptives takes a drug or herbal product that induces enzymes, including CYP3A4, that metabolize contraceptive hormones, counsel her to use additional contraception or a different method of contraception. Drugs or herbal products that induce such enzymes may decrease the plasma concentrations of contraceptive hormones, and may decrease the effectiveness of hormonal contraceptives or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include: barbiturates bosentan carbamazepine felbamate griseofulvin oxcarbazepine phenytoin rifampin St. John’s wort topiramate HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma levels of the estrogen and progestin have been noted in some cases of co-administration of HIV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors. Antibiotics: There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids. Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. 7.2 Increase in Plasma Levels of Ethinyl Estradiol Associated with Co-Administered Drugs Co-administration of atorvastatin and certain combination oral contraceptives containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol levels, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels. 7.3 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer LAYOLIS Fe with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions ( 5.4 )] . 7.4 Changes in Plasma Levels of Co-Administered Drugs COCs containing some synthetic estrogens (e.g., ethinyl estradiol) may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma concentrations of lamotrigine, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary....

Contraindications

4 CONTRAINDICATIONS LAYOLIS 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 ( 5.5 )] - Have diabetes with vascular disease [see Warnings and Precautions ( 5.7 )] - Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 [see Warnings and Precautions ( 5.8 )] Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions ( 5.2 )] Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.7 ), and Clinical Pharmacology ( 12.3 )] Undiagnosed abnormal uterine bleeding [see Warnings and Precautions ( 5.9 )] 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 ( 5.4 )] A high risk of arterial or venous thrombotic diseases. ( 4 ) Undiagnosed abnormal uterine bleeding. ( 4 ) Breast cancer ( 4 ) Liver tumors or liver disease ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, LAYOLIS Fe should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to COCs before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.

Overdosage

10 OVERDOSAGE There have been no reports of serious ill effects from overdose of oral contraceptives including ingestion by children. Overdosage may cause nausea, and withdrawal bleeding may occur in females.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied LAYOLIS Fe ® is available in cartons of 3 blister cards (dispensers) (NDC 52544-064-31). Each blister card (28 tablets) contains in the following order: 24 light green, round tablets (active) imprinted with “WC” on one side and “483” on the other and each containing 0.8 mg norethindrone and 0.025 mg ethinyl estradiol. 4 brown, round tablets (non-hormonal placebo) imprinted with “WC” on one side and “624” on the other and each containing 75 mg ferrous fumarate. 16.2 Storage Conditions Store at 20-25ºC (68-77ºF). [See USP controlled room temperature.] Keep out of reach of children. 16.1 How Supplied LAYOLIS Fe ® is available in cartons of 3 blister cards (dispensers) (NDC 52544-064-31). Each blister card (28 tablets) contains in the following order: 24 light green, round tablets (active) imprinted with “WC” on one side and “483” on the other and each containing 0.8 mg norethindrone and 0.025 mg ethinyl estradiol. 4 brown, round tablets (non-hormonal placebo) imprinted with “WC” on one side and “624” on the other and each containing 75 mg ferrous fumarate.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.