لوونورژسترل و اتینیل استرادیول و فروس فومارات

Joyeaux برای استفاده توسط زنان دارای پتانسیل باروری برای جلوگیری از بارداری نشان داده شده است. Joyeaux یک COC پروژستین/استروژن است که برای زنان دارای پتانسیل باروری برای جلوگیری از بارداری استفاده می شود. (1)

Joyeaux (قرص لوونورژسترول و اتینیل استرادیول، USP و قرص فومارات آهن) در یک کارت تاول کوچک 28 قرصی با:

• 21 قرص سفید و گرد (فعال) با علامت SZ و L2 که در طرفین مقابل آنها برجسته شده و هر کدام حاوی لوونورژسترل 0.10 میلی گرم و اتینیل استرادیول 0.02 میلی گرم است.
• 7 قرص گرد قهوه ای (دارونما غیرفعال) با علامت XI و 12 در طرف مقابل و هر کدام حاوی فروس فومارات 75 میلی گرمی قرص فومارات آهن هیچ هدف درمانی ندارد. Joyeaux از 28 قرص به ترتیب زیر تشکیل شده است ( 3 ):
• 21 قرص سفید (فعال)، هر کدام حاوی 0.1 میلی گرم لوونورژسترل و 0.02 میلی گرم اتینیل استرادیول.
• 7 قرص قهوه ای رنگ (دارونما غیر فعال) هر کدام حاوی فروس فومارات 75 میلی گرم. قرص فومارات آهن هیچ هدف درمانی ندارد. (3)

Joyeaux در زنانی که به شرایط زیر مبتلا هستند یا به آنها مبتلا هستند منع مصرف دارد: خطر بالای بیماری ترومبوتیک شریانی یا وریدی. به عنوان مثال می توان به زنانی اشاره کرد که به این موارد معروف هستند: سیگار بکشید، اگر بالای 35 سال سن داشته باشید [به هشدارها و هشدارها و اقدامات احتیاطی جعبه‌ای (5.1) مراجعه کنید]] ترومبوز ورید عمقی یا آمبولی ریه داشته باشید، اکنون یا در گذشته [به هشدارها و اقدامات احتیاطی (5.1) مراجعه کنید]] هیپرانعقادی‌های ارثی یا اکتسابی و رگ‌های خونی (5) را ببینید. بیماری عروق مغزی [به هشدارها و اقدامات احتیاطی (5.1) مراجعه کنید] بیماری عروق کرونر دارید [به هشدارها و اقدامات احتیاطی مراجعه کنید (5.1)] بیماری‌های دریچه‌ای ترومبوژنیک یا ریتم ترومبوژنیک قلب (به عنوان مثال، اندوکاردیت باکتریایی تحت حاد همراه با بیماری دریچه‌ای، یا فیبریلاسیون دهلیزی) [به هشدارها و اقدامات احتیاطی (5.1) مراجعه کنید] فشار خون بالا کنترل‌نشده را داشته باشید. بیماری عروقی [به هشدارها و اقدامات احتیاطی (5.6) مراجعه کنید] سردردهای کانونی داشته باشید علائم عصبی یا سردردهای میگرنی همراه با اورا [به هشدارها و اقدامات احتیاطی (5.7) مراجعه کنید] زنان بالای 35 سال با هر سردرد میگرنی [نگاه کنید به هشدارها و اقدامات احتیاطی (5.7)] تومورهای کبدی، خوش خیم یا بدخیم، یا بیماری کبدی [نگاه کنید به هشدارها و اقدامات احتیاطی غیرقابل تشخیصی] [به هشدارها و اقدامات احتیاطی (5.8) مراجعه کنید] بارداری، زیرا دلیلی برای استفاده وجود ندارد COCها در دوران بارداری [نگاه کنید به هشدارها و اقدامات احتیاطی (5.9) و استفاده در جمعیت‌های خاص (8.1)] تشخیص فعلی یا سابقه سرطان پستان، که ممکن است به هورمون حساس باشد [به هشدارها و اقدامات احتیاطی (5.10) مراجعه کنید] حساسیت مفرط به هر یک از اجزای ترکیبی داروی C استفاده از هپاتیت ombitasvir/paritaprevir/ritonavir، با یا بدون داسابوویر، به دلیل پتانسیل برای ارتفاعات ALT [به هشدارها و اقدامات احتیاطی (5.3) مراجعه کنید]

• خطر بالای بیماری های ترومبوتیک شریانی یا وریدی (4)
• تومورهای کبدی یا بیماری کبد (4)
• خونریزی غیر طبیعی رحم تشخیص داده نشده (4)
• بارداری (4)
• سرطان سینه (4)
• حساسیت به هر یک از اجزاء (4)
• مصرف همزمان با ترکیبات دارویی هپاتیت C حاوی امبیتاسویر/پاریتاپرویر/ریتوناویر، با یا بدون داسابوویر (4)

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 other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. Combined oral contraceptives 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 increases with use of COCs [see Warnings and Precautions ( 5.12 )] .

7.3 Concomitant Use with HCV Combination Therapy - Liver Enzyme Elevation Do not co-administer Joyeaux with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions ( 5.3 )] .

7.4 Interference with Laboratory Tests The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.

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 : hypersensitivity reactions, including pruritus, rash, urticaria, erythema Injury, poisoning, and procedural complications : injury Investigations : weight decreased Musculoskeletal and connective tissue disorders : pain in extremity, arthralgia, back pain, muscle spasm Nervous system disorders : headache, migraine, dizziness, hypoesthesia, paresthesia Psychiatric disorders : depression, insomnia, anxiety Reproductive system and breast disorders : metrorrhagia, menorrhagia, hot flush, vaginal hemorrhage Respiratory, thoracic, and mediastinal disorders : nasopharyngitis, cough Sleep disorders and disturbances : somnolence Vascular disorders : deep vein thrombosis, pulmonary embolism

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.

• Nursing mothers: Advise use of another contraceptive method. Joyeaux can decrease milk production. ( 8.2 )

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.

8.2 Lactation Risk Summary Combined hormonal contraceptives (CHCs) and/or metabolites are present in human milk and in breast-fed infants. CHCs, including Joyeaux, can reduce milk production in breast-feeding females. This reduction can occur at any time but is less likely to occur once breast-feeding is well-established. When possible, advise the nursing female to use other methods of contraception until she discontinues breast-feeding. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Joyeaux and any potential adverse effects on the breast-fed child from Joyeaux or from the underlying maternal condition.

8.4 Pediatric Use Safety and efficacy of Joyeaux have been established in women of reproductive age. Efficacy is expected to be the same in post-pubertal adolescents under the age of 18 years as for users 18 years and older. Use of this product before menarche is not indicated.

8.5 Geriatric Use Joyeaux has not been studied in postmenopausal women and is not indicated in this population.

8.6 Hepatic Impairment The pharmacokinetics of Joyeaux has not been studied in women with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded [see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )] .

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.

Safety and efficacy of Joyeaux have been established in women of reproductive age. Efficacy is expected to be the same in post-pubertal adolescents under the age of 18 years as for users 18 years and older. Use of this product before menarche is not indicated.

Joyeaux has not been studied in postmenopausal women and is not indicated in this population.

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

12.1 Mechanism of Action COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.

12.2 Pharmacodynamics No specific pharmacodynamics studies were conducted with Joyeaux.

12.3 Pharmacokinetics Absorption No specific investigation of the absolute bioavailability of levonorgestrel and ethinyl estradiol tablets USP in humans has been conducted. However, literature indicates that levonorgestrel is rapidly and completely absorbed after oral administration (bioavailability about 100%) and is not subject to first-pass metabolism. Ethinyl estradiol is rapidly and almost completely absorbed from the gastrointestinal tract but, due to first-pass metabolism in gut mucosa and liver, the bioavailability of ethinyl estradiol is between 38% and 48%. After a single dose of two levonorgestrel and ethinyl estradiol tablets to 34 women under fasting conditions, the mean (± SD) plasma area under the concentration time curve (AUC) and maximum concentration (Cmax) of levonorgestrel were 41.7 ± 18.0 ng*hour/mL and 4.4 ± 1.8 ng/mL, respectively, with a median time to maximum concentration (Tmax) of 1.0 hours. The mean (±SD) plasma AUC and Cmax of ethinyl estradiol were 1167 ± 367 pg*hour/mL and 115 ± 37 pg/mL, respectively, with a median Tmax of 1.5 hours. The plasma levonorgestrel and ethinyl estradiol pharmacokinetic profiles following a single dose of two levonorgestrel and ethinyl estradiol tablets are shown in Figure 2 . Figure 2. Mean (SD) Levonorgestrel and Ethinyl Estradiol Plasma Concentrations in 34 Subjects receiving two Levonorgestrel and Ethinyl Estradiol Tablets (0.1 mg/0.02 mg) from Levonorgestrel and Ethinyl Estradiol Tablets and Ferrous Fumarate Tablets Distribution Levonorgestrel in serum is primarily bound to SHBG. Ethinyl estradiol is about 97% bound to plasma albumin. Ethinyl estradiol does not bind to SHBG, but induces SHBG synthesis. Metabolism Levonorgestrel: The most important metabolic pathway occurs in the reduction of the Δ4-3-oxo group and hydroxylation at positions 2α, 1β, and 16β, followed by conjugation. Most of the metabolites that circulate in the blood are sulfates of 3α, 5β-tetrahydro-levonorgestrel, while excretion occurs predominantly in the form of glucuronides. Some of the parent levonorgestrel also circulates as 17β-sulfate. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation observed in levonorgestrel concentrations among users. Ethinyl estradiol: Cytochrome P450 enzymes (CYP3A4) in the liver are responsible for the 2‑hydroxylation that is the major oxidative reaction. The 2-hydroxy metabolite is further transformed by methylation and glucuronidation prior to urinary and fecal excretion. Levels of Cytochrome P450 (CYP3A) vary widely among individuals and can explain the variation in rates of ethinyl estradiol 2-hydroxylation. Ethinyl estradiol is excreted in the urine and feces as glucuronide and sulfate conjugates, and undergoes enterohepatic circulation. Excretion The elimination half-life for levonorgestrel is approximately 34 ± 14 hours following a single dose. Levonorgestrel and its metabolites are primarily excreted in the urine (40% to 68%) and about 16% to 48% are excreted in feces. The elimination half-life of ethinyl estradiol is 17 ± 5.7 hours. Figure 2

COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.

No specific pharmacodynamics studies were conducted with Joyeaux.

Absorption No specific investigation of the absolute bioavailability of levonorgestrel and ethinyl estradiol tablets USP in humans has been conducted. However, literature indicates that levonorgestrel is rapidly and completely absorbed after oral administration (bioavailability about 100%) and is not subject to first-pass metabolism. Ethinyl estradiol is rapidly and almost completely absorbed from the gastrointestinal tract but, due to first-pass metabolism in gut mucosa and liver, the bioavailability of ethinyl estradiol is between 38% and 48%. After a single dose of two levonorgestrel and ethinyl estradiol tablets to 34 women under fasting conditions, the mean (± SD) plasma area under the concentration time curve (AUC) and maximum concentration (Cmax) of levonorgestrel were 41.7 ± 18.0 ng*hour/mL and 4.4 ± 1.8 ng/mL, respectively, with a median time to maximum concentration (Tmax) of 1.0 hours. The mean (±SD) plasma AUC and Cmax of ethinyl estradiol were 1167 ± 367 pg*hour/mL and 115 ± 37 pg/mL, respectively, with a median Tmax of 1.5 hours. The plasma levonorgestrel and ethinyl estradiol pharmacokinetic profiles following a single dose of two levonorgestrel and ethinyl estradiol tablets are shown in Figure 2 . Figure 2. Mean (SD) Levonorgestrel and Ethinyl Estradiol Plasma Concentrations in 34 Subjects receiving two Levonorgestrel and Ethinyl Estradiol Tablets (0.1 mg/0.02 mg) from Levonorgestrel and Ethinyl Estradiol Tablets and Ferrous Fumarate Tablets Distribution Levonorgestrel in serum is primarily bound to SHBG. Ethinyl estradiol is about 97% bound to plasma albumin. Ethinyl estradiol does not bind to SHBG, but induces SHBG synthesis. Metabolism Levonorgestrel: The most important metabolic pathway occurs in the reduction of the Δ4-3-oxo group and hydroxylation at positions 2α, 1β, and 16β, followed by conjugation. Most of the metabolites that circulate in the blood are sulfates of 3α, 5β-tetrahydro-levonorgestrel, while excretion occurs predominantly in the form of glucuronides. Some of the parent levonorgestrel also circulates as 17β-sulfate. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation observed in levonorgestrel concentrations among users. Ethinyl estradiol: Cytochrome P450 enzymes (CYP3A4) in the liver are responsible for the 2‑hydroxylation that is the major oxidative reaction. The 2-hydroxy metabolite is further transformed by methylation and glucuronidation prior to urinary and fecal excretion. Levels of Cytochrome P450 (CYP3A) vary widely among individuals and can explain the variation in rates of ethinyl estradiol 2-hydroxylation. Ethinyl estradiol is excreted in the urine and feces as glucuronide and sulfate conjugates, and undergoes enterohepatic circulation. Excretion The elimination half-life for levonorgestrel is approximately 34 ± 14 hours following a single dose. Levonorgestrel and its metabolites are primarily excreted in the urine (40% to 68%) and about 16% to 48% are excreted in feces. The elimination half-life of ethinyl estradiol is 17 ± 5.7 hours. Figure 2

, Mutagenesis, Impairment of Fertility [see Warnings and Precautions ( 5.12 ) and Use in Specific Populations ( 8.1 )]

17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information and Instructions for Use). Counsel patients on the following information:

• Cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs [see Boxed Warning ] .
• Increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC [see Warnings and Precautions ( 5.1 )] .
• Joyeaux does not protect against HIV-infection (AIDS) and other sexually transmitted diseases.
• Joyeaux is not to be used during pregnancy; if pregnancy occurs during use of Joyeaux, instruct the patient to stop further use [see Use in Specific Populations ( 8.1 )] .
• Take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event pills are missed [see Dosage and Administration ( 2.3 )] .
• Use a back-up or alternative method of contraception when enzyme inducers are used with Joyeaux [see Drug Interactions ( 7.1 )] .
• COCs may reduce breast milk production; this is less likely to occur if breastfeeding is well established [see Use in Specific Populations ( 8.2 )] .
• A woman who starts COCs postpartum and who has not yet had a period should use an additional method of contraception until she has taken a white tablet for 7 consecutive days [see Dosage and Administration ( 2.2 )] .
• Amenorrhea may occur. Consider pregnancy in the event of amenorrhea at the time of the first missed period. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles [see Warnings and Precautions ( 5.8 )] . JOYEAUX ® is a registered trademark of Xiromed Pharma España, S.L. Manufactured by: Laboratorios León Farma, S.A., León, Spain for Xiromed, LLC, Florham Park, NJ 07932 Date: 01/2024 PI-177-01