Levonorgestrel And Ethinyl Estradiol And Ethinyl Estradiol
FDA Drug Information • Also known as: Ashlyna, Levonorgestrel And Ethinyl Estradiol And Ethinyl Estradiol, Lo Simpesse, Rosyrah, Simpesse
- Brand Names
- Ashlyna, Levonorgestrel And Ethinyl Estradiol And Ethinyl Estradiol, Lo Simpesse, Rosyrah, Simpesse
- 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 contraceptives (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, including Simpesse, are contraindicated in 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. Simpesse is contraindicated in women over 35 years old who smoke. Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use.
Description
11 DESCRIPTION Simpesse (levonorgestrel and ethinyl estradiol tablets USP and ethinyl estradiol tablets USP) is an extended-cycle oral contraceptive consisting of 84 white tablets each containing 0.15 mg of levonorgestrel USP, a synthetic progestogen and 0.03 mg of ethinyl estradiol USP, and 7 light blue tablets containing 0.01 mg of ethinyl estradiol USP. 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-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol, (17α)-. Each white tablet contains the following inactive ingredients : croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Each light blue tablet contains the following inactive ingredients : colloidal silicon dioxide, FD&C Blue No. 1, lactose monohydrate, povidone, pregelatinized starch (maize), stearic acid, and vitamin E. Levonorgestrel Chemical Structure Ethinyl Estradiol Chemical Structure
What Is Levonorgestrel And Ethinyl Estradiol And Ethinyl Estradiol Used For?
1 INDICATIONS AND USAGE Simpesse ® (levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets) is indicated for use by females of reproductive potential to prevent pregnancy. Simpesse is a combination of levonorgestrel, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Take one tablet daily by mouth at the same time every day for 91 days in the order directed on the blister pack. ( 2 ) 2.1 How to Start and Take Simpesse Begin Simpesse on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, take the first white tablet that day. For each 91-day course, take in the following order: 1. Start the first white tablet on the first Sunday after onset of menstruation. Then take one white tablet daily for 84 consecutive days. Use a non-hormonal back-up method of contraception (such as condoms and spermicide) until a white tablet has been taken daily for 7 consecutive days. 2. Then take one light blue tablet for 7 consecutive days. Bleeding should occur during the 7 days that the light blue tablets are taken. Begin the next and all subsequent 91-day cycles without interruption on the same day of the week (Sunday) on which the patient began her first dose of Simpesse, following the same schedule: 84 days taking a white tablet followed by 7 days taking a light blue tablet. If the patient does not immediately start her next pill pack, instruct her to protect herself from pregnancy by using a non-hormonal back-up method of contraception until she has taken a white tablet daily for 7 consecutive days. Switching to Simpesse from another oral hormonal contraceptive or from another contraceptive method (transdermal patch, vaginal ring, injection, intrauterine contraceptive, implant) Start on the Sunday after the patient’s next period starts. Use additional non-hormonal contraceptive (such as condoms and spermicide) until the patient has taken a white tablet for 7 consecutive days. Starting Simpesse after Abortion or Miscarriage First-trimester Simpesse may be started on the Sunday after an abortion or miscarriage. The patient must use additional non-hormonal contraception (such as condoms and spermicide) until the patient has taken a white tablet for 7 consecutive days. Second-trimester Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Simpesse following the instructions for women not currently using hormonal contraception. Use additional non-hormonal contraception (such as condoms and spermicide) until the patient has taken a white tablet for 7 consecutive days [see Contraindications (4) and Warnings and Precautions (5.1) ]. Starting Simpesse after Childbirth Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Simpesse following the instructions for women not currently using hormonal contraception. Use additional non-hormonal contraception (such as condoms and spermicide) until the patient has taken a white tablet for 7 consecutive days [see Contraindications (4) and Warnings and Precautions (5.1) ]. If the woman has not yet had a period postpartum, consider the possibility of...
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) ] The most common adverse reactions (≥5%) in clinical trials for Simpesse are irregular and/or heavy uterine bleeding, weight gain, and acne. (6) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 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 the rates in the clinical trials of another drug and may not reflect the rates observed in practice. The clinical trial that evaluated the safety and efficacy of Simpesse was a 12-month, randomized, multicenter, open-label study, which enrolled women aged 18 to 40, of whom 1,006 took at least one dose of Simpesse. Adverse Reactions Leading to Study Discontinuation: 16.3% of the women discontinued from the clinical trial due to an adverse reaction; the most common adverse reactions (≥ 1% of women) leading to discontinuation were irregular and/or heavy uterine bleeding (5.9%), weight gain (2.4%), mood changes (1.5%), and acne (1.0%). Common Treatment-Emergent Adverse Reactions (≥ 5% of women): irregular and/or heavy uterine bleeding (17%), weight gain (5%), acne (5%). Serious Adverse Reactions: migraine, cholecystitis, cholelithiasis, pancreatitis, abdominal pain, and major depressive disorder. 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 to 1.12 (Figure 3). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 3). 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 3: 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 adverse reactions have been identified during post-approval use of Simpesse. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency of establish a causal relationship to drug exposure. Gastrointestinal disorders : abdominal distension, vomiting General disorders and administration site conditions : chest pain, fatigue, malaise, edema peripheral, pain Immune system disorders : hypersensitivity reaction Investigations: blood pressure increased Musculoskeletal and connective tissue disorders : muscle spasms, pain in extremity Nervous system disorders : dizziness, loss of consciousness Psychiatric disorders : insomnia Reproductive and breast disorders : dysmenorrhea Respiratory, thoracic and mediastinal disorders: pulmonary embolism, pulmonary thrombosis Skin and subcutaneous tissue disorders : alopecia Vascular disorders : thrombosis Figure 3
Drug Interactions
7 DRUG INTERACTIONS 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 Simpesse. Enzyme inducers (e.g., CYP3A4): May decrease the effectiveness of Simpesse or increase breakthrough bleeding. Counsel patients to use a back-up method or alternative method of contraception when enzyme inducers are used with Simpesse. ( 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: Table 4 includes substances that demonstrated an important drug interaction with Simpesse. Table 4: Significant Drug Interactions Involving Substances That Affect COCs 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 CHC. Prevention or management Administer 4 or more hours apart to attenuate this drug interaction. a Induction potency of St. John’s wort may vary widely based on preparation. 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...
Contraindications
4 CONTRAINDICATIONS Simpesse 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 females who are known to: – Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1) ]. – Have current or history of deep vein thrombosis or pulmonary embolism [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 or hypertension with vascular disease [see Warnings and Precautions (5.3) ]. – Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or with vascular disease or other end-organ damage, or diabetes mellitus of > 20 years duration [see Warnings and Precautions (5.7) ]. – Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.8) ]. Current diagnosis of, or history of, breast cancer, which may be hormone sensitive [see Warnings and Precautions (5.11) ]. Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6) ]. 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 )...
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, Simpesse should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital 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 uterine bleeding in females and nausea.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Simpesse tablets (levonorgestrel and ethinyl estradiol tablets USP 0.15 mg/0.03 mg and ethinyl estradiol tablets USP 0.01 mg) are available in Extended-Cycle Wallets, each containing a 13-week supply of tablets: 84 white tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol, and 7 light blue tablets each containing 0.01 mg of ethinyl estradiol. The white tablets are round, biconvex, beveled-edge, debossed with “S” on one side and “27” on other side. The light blue tablets are mottled, round, biconvex, beveled-edge, debossed with “S” on one side and “45” on other side. Pouch of 1 Extended-Cycle Wallet NDC 65862-864-94 Carton of 2 Pouches NDC 65862-864-95 Storage and Handling Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
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.