DailyMed Label: LEVONORGESTREL AND ETHINYL ESTRADIOL

DailyMed Label: Levonorgestrel and Ethinyl Estradiol

2024

DailyMed Prescription

Levonorgestrel and Ethinyl Estradiol

Levonorgestrel and Ethinyl Estradiol

Naari Pte Limited

NDC: 79929-003

NDC: 79929-003

NDC: 79929-003

NDC: 79929-003

NDC: 79929-003

NDC: 79929-003

Levonorgestrel and Ethinyl Estradiol Tablets USP are a combination oral contraceptive (COC) consisting of 21 light-orange active tablets, each containing 0.15 mg of levonorgestrel, a synthetic progestin and 30 mcg of ethinyl estradiol, an estrogen, and 7 pink inert tablets (without hormones). The structural formulas for the active components are: Levonorgestrel is chemically 18, 19-Dinorpregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-,(17α)-(-)-. Ethinyl Estradiol is 19-nor-17α-pregna-1, 3, 5(10)-trien-20-yne-3, 17-diol. Each light-orange active tablet contains the following inactive ingredients: lactose monohydrate, FD&C Yellow No. 6, microcrystalline cellulose, povidone K-30, polacrilin potassium and magnesium stearate. Each pink inert tablet contains the following inactive ingredients: lactose monohydrate, FD&C Red no. 40 aluminum lake, microcrystalline cellulose, povidone K-30, croscarmellose sodium and magnesium stearate. Levonorgestrel Chemical Structure Ethinyl Estradiol Chemical Structure

Levonorgestrel and ethinyl estradiol tablets are indicated for use by females of reproductive potential to prevent pregnancy.

Levonorgestrel and ethinyl estradiol tablets are contraindicated in females who are known to have 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 (1) ]. - Have current or history of deep vein thrombosis or pulmonary embolism [see WARNINGS (1) ]. - Have cerebrovascular disease [see WARNINGS (1) ]. - Have coronary artery disease [see WARNINGS (1) ]. - Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see WARNINGS (1) ]. - Have inherited or acquired hypercoagulopathies [see (1) ]. - Have uncontrolled hypertension or hypertension with vascular disease [see WARNINGS (4) ]. - Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or vascular disease or other end-organ damage, or diabetes mellitus of >20 years duration [see WARNINGS (8) ]. - Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see WARNINGS (9) ]. Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive. Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see WARNINGS (2) ]. Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see WARNINGS (6) ]. Undiagnosed abnormal uterine bleeding [see WARNINGS (10) ].

Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult [see WARNINGS (7) ]. In patients with familial defects of lipoprotein metabolism receiving estrogen-containing preparations, there have been case reports of significant elevations of plasma triglycerides leading to pancreatitis. Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. Diarrhea and/or vomiting may reduce hormone absorption (see DOSAGE AND ADMINISTRATION ). The sections below provide information on substances for which data on drug interactions with COCs are available. There is little information available about the clinical effect of most drug interactions that may affect COCs. However, based on the known pharmacokinetic effects of these drugs, clinical strategies to minimize any potential adverse effect on contraceptive effectiveness or safety are suggested. Consult the approved product labeling of all concurrently used drugs to obtain further information about interactions with COCs or the potential for metabolic enzyme or transporter system alterations. No drug-drug interaction studies were conducted with levonorgestrel and ethinyl estradiol tablets. Substances Decreasing the Plasma Concentrations of COCs and Potentially Diminishing the Efficacy of COCs: Table 1 includes substances that demonstrated an important drug interaction with levonorgestrel and ethinyl estradiol tablets. Table 1: Significant Drug Interactions Involving Substances That Affect COCs a Induction potency of St. John’s wort may vary widely based on preparation. Metabolic Enzyme Inducers Clinical effect Concomitant use of COCs with metabolic enzyme inducers may decrease the plasma concentrations of the estrogen and/or progestin component of COCs. Decreased exposure of the estrogen and/or progestin component of COCs may potentially diminish the effectiveness of COCs and may lead to contraceptive failure or an increase in breakthrough bleeding. Prevention or management Counsel females to use an alternative method of contraception or a backup method when enzyme inducers are used with COCs. Continue backup contraception for 28 days after discontinuing the enzyme inducer to maintain contraceptive reliability. Examples Aprepitant, barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, rifabutin, rufinamide, topiramate, products containing St. John’s wort a , and certain protease inhibitors (see separate section on protease inhibitors below). Colesevelam Clinical effect Concomitant use of COCs with colesevelam significantly decreases systemic exposure of ethinyl estradiol. Decreased exposure of the estrogen component of COCs may potentially reduce contraceptive efficacy or result in an increase in breakthrough bleeding, depending on the strength of ethinyl estradiol in the COC. Prevention or management Administer 4 or more hours apart to attenuate this drug interaction. Substances increasing the systemic exposure of COCs: Co-administration of atorvastatin or rosuvastatin and COCs containing ethinyl estradiol increase systemic exposure of ethinyl estradiol by approximately 20 to 25 percent. Ascorbic acid and acetaminophen may increase systemic exposure of ethinyl estradiol, possibly by inhibition of conjugation. CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, 7 or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of COCs. Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant decreases in systemic exposure of the estrogen and/or progestin have been noted when COCs are co-administered with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (e.g., boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine). In contrast, significant increases in systemic exposure of the estrogen and/or progestin have been noted when COCs are co-administered with certain other HIV protease inhibitors (e.g., indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., etravirine). Table 2 provides significant drug interaction information for drugs co-administered with levonorgestrel and ethinyl estradiol tablets. Table 2: Significant Drug Interaction Information for Drugs Co-Administered With COCs Lamotrigine Clinical effect Concomitant use of COCs with lamotrigine may significantly decrease systemic exposure of lamotrigine due to induction of lamotrigine glucuronidation. Decreased systemic exposure of lamotrigine may reduce seizure control. Prevention or management Dose adjustment may be necessary. Consult the approved product labeling for lamotrigine. Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of COCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin (see Warnings, EFFECT ON BINDING GLOBULINS ). Prevention or management The dose of replacement thyroid hormone or cortisol therapy may need to be increased. Consult the approved product labeling for the therapy in use (see Warnings, EFFECT ON BINDING GLOBULINS ). Other Drugs Clinical effect Concomitant use of COCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. Concomitant use with ethinyl estradiol-containing COCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole). Prevention or management The dosage of drugs that can be affected by this interaction may need to be increased. Consult the approved product labeling for the concomitantly used drug. Do not co-administer Levonorgestrel and Ethinyl Estradiol Tablets with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, [see Warnings (5)], and glecaprevir/pibrentasvir due to potential for ALT elevations. The use of COCs may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins. See WARNINGS (11) . Risk Summary Discontinue Levonorgestrel and ethinyl estradiol tablets if pregnancy occurs because there is no reason to use COCs in 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. Animal studies to evaluate embryo/fetal toxicity were not conducted. 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. Risk Summary Contraceptive hormones and/or metabolites are present in human milk. COCs 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. (see DOSAGE AND ADMINISTRATION ). The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for levonorgestrel and ethinyl estradiol tablets and any potential adverse effects on the breast-fed child from levonorgestrel and ethinyl estradiol tablets or from the underlying maternal condition. Safety and efficacy of levonorgestrel and ethinyl estradiol tablets have been established in females of reproductive potential. Use of levonorgestrel and ethinyl estradiol tablets before menarche is not indicated. Levonorgestrel and ethinyl estradiol tablets has not been studied in postmenopausal women and is not indicated in this population. Counsel patients that 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 and CONTRAINDICATIONS). Counsel patients that this product does not protect against HIV-infection (AIDS) and other sexually transmitted infections. Counsel patients to 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). Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs [see PRECAUTIONS (4.1)]. Counsel patients who are breastfeeding or who desire to breastfeed that COCs may reduce breast milk production. This is less likely to occur if breastfeeding is well established [see PRECAUTIONS (4.1)]. Counsel any patient who starts levonorgestrel and ethinyl estradiol tablets postpartum, and who has not yet had a period, to use an additional method of contraception until she has taken a light-orange tablet for 7 consecutive days [see PRECAUTIONS (4.1)]. Counsel patients that amenorrhea may occur. Pregnancy should be considered in the event of amenorrhea, and should be ruled out if amenorrhea is associated with symptoms of pregnancy, such as morning sickness or unusual breast tenderness [see PRECAUTIONS (4.1)]. Depression may occur. Women should contact their healthcare provider if depression occurs, including shortly after initiating the treatment [see WARNINGS (11)].

Levonorgestrel and Ethinyl Estradiol Tablets USP 0.15 mg/0.03 mg are available in blister pack, containing 28 Tablets: 21 Active Tablets: Light orange color, round, uncoated tablets debossed with 'EF1' on one side and plain on other side, tablets may have mottled appearance on either of the surface. 7 Inert Tablets: Pink color, round, uncoated tablets debossed with 'EF2' on one side and plain on other side, tablets may have mottled appearance on either of the surface. NDC 79929-003-05 The blister packs of 3 are available in box. Store at 20º to 25°C (68° to 77º F) [See USP Controlled Room Temperature]. Manufactured For: Naari Pte Limited 36 Robinson Road, #13-06 City House, Singapore 068877 Issued December 2021

Combination oral contraceptives prevent pregnancy primarily by suppressing ovulation.

[LEE-voe-nor-JES-trel and EH-thih-nill-ess-tra-DYE-ole] What is the most important information I should know about Levonorgestrel and ethinyl estradiol tablets? Do not use Levonorgestrel and ethinyl estradiol tablets if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from hormonal birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke. What is Levonorgestrel and ethinyl estradiol tablets? Levonorgestrel and ethinyl estradiol tablets are a birth control pill (oral contraceptive) used by women to prevent pregnancy. How does Levonorgestrel and ethinyl estradiol tablets work for contraception? Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The better you follow the directions, the less chance you have of getting pregnant. Based on the results of clinical studies, about 1 to 5 out of 100 women may get pregnant during the first year they use levonorgestrel and ethinyl estradiol tablets. The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant. Who should not take Levonorgestrel and ethinyl estradiol tablets? Do not take levonorgestrel and ethinyl estradiol tablets if you: smoke and are over 35 years of age had blood clots in your arms, legs, lungs, or eyes had a problem with your blood that makes it clot more than normal have certain heart valve problems or irregular heart beat had a stroke had a heart attack have high blood pressure that cannot be controlled by medicine have diabetes with kidney, eye, nerve, or blood vessel damage have certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or any migraine headaches if you are over 35 years of age had breast cancer or any cancer that is sensitive to female hormones have liver problems, including liver tumors have any unexplained vaginal bleeding are pregnant take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme “alanine aminotransferase” (ALT) in the blood. If any of these conditions happen while you are taking levonorgestrel and ethinyl estradiol tablets, stop taking levonorgestrel and ethinyl estradiol tablets right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking levonorgestrel and ethinyl estradiol tablets. What should I tell my healthcare provider before taking levonorgestrel and ethinyl estradiol tablets? Tell your healthcare provider if you: are pregnant or think you may be pregnant are depressed now or have been depressed in the past had yellowing of your skin or eyes (jaundice) caused by pregnancy (cholestasis of pregnancy) are breastfeeding or plan to breastfeed. Levonorgestrel and ethinyl estradiol may decrease the amount of breast milk you make. A small amount of the hormones in levonorgestrel and ethinyl estradiol may pass into your breast milk. Talk to your healthcare provider about the best birth control method for you while breastfeeding. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Levonorgestrel and ethinyl estradiol tablets may affect the way other medicines work, and other medicines may affect how well levonorgestrel and ethinyl estradiol tablets works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I take Levonorgestrel and ethinyl estradiol tablets? Read the Instructions for Use at the end of this Patient Information. What are the possible serious side effects of Levonorgestrel and ethinyl estradiol tablets? Like pregnancy, levonorgestrel and ethinyl estradiol tablets may cause serious side effects, including blood clots in your lungs, heart attack, or a stroke that may lead to death. Some other examples of serious blood clots include blood clots in the legs or eyes. Serious blood clots can happen especially if you smoke, are obese, or are older than 35 years of age. Serious blood clots are more likely to happen when you: first start taking birth control pills restart the same or different birth control pills after not using them for a month or more Call your healthcare provider or go to a hospital emergency room right away if you have: leg pain that will not go away sudden severe shortness of breath sudden change in vision or blindness chest pain a sudden, severe headache unlike your usual headaches weakness or numbness in your arm or leg trouble speaking Other serious side effects include: liver problems, including: rare liver tumors jaundice (cholestasis), especially if you previously had cholestasis of pregnancy. Call your healthcare provider if you have yellowing of your skin or eyes. high blood pressure. You should see your healthcare provider for a yearly check of your blood pressure. gallbladder problems changes in the sugar and fat (cholesterol and triglycerides) levels in your blood new or worsening headaches, including migraine headaches irregular or unusual vaginal bleeding and spotting between your menstrual periods, especially during the first 3 months of taking levonorgestrel and ethinyl estradiol tablets. depression There may be slight increases in the risk of breast cancer among current users of hormonal birth control pills with longer duration of use of 8 years or more. swelling of your skin especially around your mouth, eyes, and in your throat (angioedema). Call your healthcare provider if you have a swollen face, lips, mouth tongue or throat, which may lead to difficulty swallowing or breathing. Your chance of having angioedema is higher if you have a history of angioedema. dark patches of skin around your forehead, nose, cheeks and around your mouth, especially during pregnancy (chloasma). Women who tend to get chloasma should avoid spending a long time in sunlight, tanning booths, and under sun lamps while taking levonorgestrel and ethinyl estradiol tablets. Use sunscreen if you have to be in the sunlight. What are the most common side effects of oral contraceptives? nausea vomiting bleeding between menstrual periods weight gain breast tenderness difficulty wearing contact lenses These are not all the possible side effects of levonorgestrel and ethinyl estradiol tablets. For more information, ask your healthcare provider or pharmacist. You may report side effects to the FDA at 1-800-FDA-1088. What else should I know about taking Levonorgestrel and ethinyl estradiol tablets? If you are scheduled for any lab tests, tell your healthcare provider you are taking levonorgestrel and ethinyl estradiol tablets. Certain blood tests may be affected by levonorgestrel and ethinyl estradiol tablets. Levonorgestrel and ethinyl estradiol tablets does not protect against HIV-infection (AIDS) and other sexually transmitted infections. How should I store Levonorgestrel and ethinyl estradiol tablets? Store levonorgestrel and ethinyl estradiol tablets at room temperature between 68°F to 77°F (20°C to 25°C). Protect from light. General information about the safe and effective use of Levonorgestrel and ethinyl estradiol tablets. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use levonorgestrel and ethinyl estradiol tablets for a condition for which it was not prescribed. Do not give levonorgestrel and ethinyl estradiol tablets to other people, even if they have the same symptoms that you have. This Patient Information Leaflet summarizes the most important information about levonorgestrel and ethinyl estradiol tablets. You can ask your pharmacist or healthcare provider for information about levonorgestrel and ethinyl estradiol tablets that is written for health professionals. For more information, go to www.fda.gov/medwatch or call FDA at 1-800-FDA-1088. Does hormonal birth control cause cancer? It is not known if hormonal birth control pills causes breast cancer. Some studies, but not all, suggest that there could be a slight increase in the risk of breast cancer among current users with longer duration of use. If you have breast cancer now, or have had it in the past, do not use hormonal birth control because some breast cancers are sensitive to hormones. What if I want to become pregnant? You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill. What should I know about my period when taking levonorgestrel and ethinyl estradiol tablets? Your periods may be lighter and shorter than usual. Some women may miss a period. Irregular vaginal bleeding or spotting may happen while you are taking levonorgestrel and ethinyl estradiol tablets, especially during the first few months of use. This usually is not a serious problem. It is important to continue taking your pills on a regular schedule to prevent a pregnancy. What are the ingredients in levonorgestrel and ethinyl estradiol tablets? Active ingredients : Each light-orange pill contains levonorgestrel and ethinyl estradiol. Inactive ingredients : Light-orange pills: lactose monohydrate, FD&C Yellow No. 6, microcrystalline cellulose, povidone K-30, polacrilin potassium and magnesium stearate. Pink pills: lactose monohydrate, FD&C Red no. 40 aluminum lake, microcrystalline cellulose, povidone K-30, croscarmellose sodium and magnesium stearate. Manufactured For: Naari Pte Limited 36 Robinson Road, #13-06 City House, Singapore 068877 Issued December 2021 Levonorgestrel and Ethinyl Estradiol Tablets-Carton

Levonorgestrel and Ethinyl Estradiol USP 0.15 mg/0.03 mg Tablet figure-3