Levonorgestrel And Ethinyl Estradiol And Ferrous Fumarate

FDA Drug Information • Also known as: Joyeaux

Brand Names: Joyeaux
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 are contraindicated in women who are over 35 years of age and smoke [see Contraindications ( 4 )] . WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS See full prescribing information for complete boxed warning. Joyeaux is contraindicated in women over 35 years old who smoke. ( 4 ) Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COC) use. ( 4 )

Description

11 DESCRIPTION Joyeaux (levonorgestrel and ethinyl estradiol tablets, USP, and ferrous fumarate tablets) provides an oral contraceptive regimen consisting of 21 white active tablets and 7 brown inactive tablets.

21 white active tablets each containing 0.10 mg of levonorgestrel, d(-)-13β-ethyl-17α-ethinyl-17β-hydroxygon-4-en-3-one, a totally synthetic progestogen, and 0.02 mg of ethinyl estradiol, 17α-ethinyl-1,3,5(10)-estratriene-3, 17β-diol, an estrogenic compound

7 brown inactive tablets each containing 75 mg ferrous fumarate The inactive ingredients present in the white active tablets are corn starch, crospovidone, lactose monohydrate, magnesium stearate, methanol, methylene chloride, povidone, and pregelatinized starch. The inactive ingredients in the brown inactive tablets are ferrous fumarate, lactose monohydrate, magnesium stearate, mannitol, microcrystalline cellulose, peppermint flavor, povidone, sodium starch glycolate, and sucralose. Levonorgestrel has the empirical formula of C 21 H 28 O 2 and the molecular weight of 312.4, and ethinyl estradiol has the empirical formula of C 20 H 24 O 2 and the molecular weight of 296.4. The molecular structures are provided below: Molecular Structures

What Is Levonorgestrel And Ethinyl Estradiol And Ferrous Fumarate Used For?

1 INDICATIONS AND USAGE Joyeaux is indicated for use by females of reproductive potential to prevent pregnancy. Joyeaux is a progestin/estrogen COC indicated for use by females of reproductive potential to prevent pregnancy. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION

Take one tablet by mouth at the same time every day. ( 2.1 )

Take tablets in the order directed on the blister pack. ( 2.1 ) 2.1 How to Start Joyeaux Joyeaux is dispensed in a blister card [see How Supplied/Storage and Handling ( 16 )] . Joyeaux may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration. 2.2 How to Take Joyeaux Joyeaux (white active tablets and brown placebo tablets) are swallowed whole once a day Table 1: Instructions for Administration of Joyeaux Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling. Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start) Important: Consider the possibility of ovulation and conception prior to initiation of this product. Tablet Color: Joyeaux active tablets are white (Day 1 to Day 21). Joyeaux placebo tablets are brown (Day 22 to Day 28). Day 1 Start:

Take first white active tablet on the first day of menses.

Take subsequent white active tablets once daily at the same time each day for a total of 21 days.

Take one brown placebo tablet daily for 7 days and at the same time of day that active tablets were taken.

Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet). Sunday Start:

Take first active tablet on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of the patient’s first cycle pack of Joyeaux.

Take subsequent white tablets once daily at the same time each day for a total of 21 days.

Take one brown placebo tablet daily for the following 7 days and at the same time of day that active tablets were taken.

Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed. Switching to Joyeaux from another hormonal contraceptive Start on the same day that a new pack of the previous hormonal contraceptive would have started. Switching from another contraceptive method to Joyeaux Start Joyeaux:

Transdermal patch

On the day when next application would have been scheduled

Vaginal ring

On the day when next insertion would have been scheduled

Injection

On the day when next injection would have been scheduled

Intrauterine contraceptive

On the day of removal

If the IUD is not removed on first day of the patient’s menstrual cycle, additional non-hormonal contraceptive (such as condoms or spermicide) is needed for the first seven days of the first cycle pack.

Implant

On the day of removal Starting Joyeaux...

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 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 Common adverse reactions (≥2% of women): headache (14%), metrorrhagia (8%), dysmenorrhea and nausea (7% each), abdominal pain and breast pain (4% each), emotional lability and acne (3% each), and depression, amenorrhea, and vaginal moniliasis (2% each) ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Xiromed, LLC at 844-XIROMED (844-947-6633) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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 clinical practice. In a clinical trial with levonorgestrel 0.1 mg and ethinyl estradiol 0.02 mg tablets, a total of 1477 healthy women of child-bearing potential were enrolled and had 7870 cycles of exposure. Of these, 792 subjects had completed 6 cycles of treatment. The women ranged in age from 17 to 49 years and 87% were Caucasian. Common Adverse Reactions (≥ 2% of women):

headache (14%)

metrorrhagia (8%)

dysmenorrhea (7%)

nausea (7%)

abdominal pain (4%)

breast pain (4%)

emotional lability (3%)

acne (3%)

depression (2%)

amenorrhea (2%)

vaginal moniliasis (2%) At the time of the report, 133 (9%) subjects had withdrawn from the study due to adverse events. The most frequent were due to headache and metrorrhagia (1% each). Other adverse events occurring in < 1% of those who discontinued included amenorrhea, depression, emotional lability, hypertension, acne, menorrhagia, nausea, hypercholesterolemia, weight gain, dysmenorrhea, and flatulence. All other reasons for discontinuation were reported by 3 or fewer subjects. 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. 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. The following additional adverse drug reactions have been reported from worldwide postmarketing experience with levonorgestrel 0.1 mg and ethinyl estradiol 0.02 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 establish a causal relationship to drug exposure. Cardiac disorder : chest pain, dyspnea, palpitations Gastrointestinal disorders : abdominal pain, nausea, vomiting, diarrhea General disorders and administration site conditions : chest pain, fatigue, pain, malaise, injection site pain or erythema, feeling abnormal, pyrexia, condition aggravated, asthenia Immune system disorders :...

Drug Interactions

7 DRUG INTERACTIONS Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. 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 Effects of Other Drugs on Combined Oral Contraceptives Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John’s wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Colesevelam: Colesevelam, a bile acid sequestrant, given together with a COC, has been shown to significantly decrease the AUC of ethinyl estradiol (EE). The drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart. Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20-25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors, such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. 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/or progestin have been noted in some cases of co-administration with HIV/HCV protease inhibitors and non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, tipranavir/ritonavir, boceprevir, telaprevir, nevirapine and efavirenz] or increase [e.g., indinavir, atazanavir/ritonavir and etravirine]). 7.2 Effects of Combined Oral Contraceptives on Other Drugs Combined oral contraceptives containing EE may inhibit the metabolism of...

Contraindications

4 CONTRAINDICATIONS Joyeaux is contraindicated in females who are known to have or develop the following conditions: A high risk of arterial or venous thrombotic disease. 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 inherited or acquired hypercoagulopathies [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 uncontrolled hypertension [see Warnings and Precautions ( 5.4 )] Have diabetes mellitus with vascular disease [see Warnings and Precautions ( 5.6 )] Have headaches with focal neurological symptoms or have migraine headaches with aura [see Warnings and Precautions ( 5.7 )] Women over age 35 with any migraine headaches [see Warnings and Precautions ( 5.7 )] Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions ( 5.2 )] Undiagnosed abnormal uterine bleeding [see Warnings and Precautions ( 5.8 )] Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions ( 5.9 ) 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 )] Hypersensitivity to any of the components 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 )

Liver tumors or liver disease ( 4 )

Undiagnosed abnormal uterine bleeding ( 4...

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Joyeaux is contraindicated in pregnancy because there is no reason to use combined hormonal contraceptives (CHCs) in pregnancy. Discontinue Joyeaux if pregnancy occurs. Based on epidemiologic studies and meta-analyses, there is little or no increased risk of birth defects in the children of females who inadvertently use COCs during early pregnancy (See Data ) . 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. Human Data 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.

Overdosage

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

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Joyeaux is available in a blister pack containing 28 tablets arranged in 3 rows of 7 active tablets and 1 row of inactive tablets, as follows:

21 active tablets: white, round tablet debossed with “SZ” on one side and "L2" on the other side; each tablet containing levonorgestrel 0.10 mg and ethinyl estradiol 0.02 mg

7 inactive tablets: brown, round tablet debossed with “XI” on one side and "12" on the other side; each tablet containing ferrous fumarate 75 mg Joyeaux is available as a Carton of 3 blister packs (NDC 70700-177-85) 16.2 Storage Conditions

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP controlled room temperature].

Protect from light Keep out of the reach of children.

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.