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Drospirenone And Ethinyl Estradiol
FDA Drug Information • Also known as: Drospirenone And Ethinyl Estradiol, Jasmiel, Lo-Zumandimine, Nikki, Ocella, Syeda, Vestura, Yasmin,...
- Brand Names
- Drospirenone And Ethinyl Estradiol, Jasmiel, Lo-Zumandimine, Nikki, Ocella, Syeda, Vestura, Yasmin, Yaz, Zumandimine
- 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 should not be used by 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.
Women over 35 years old who smoke should not use drospirenone and ethinyl estradiol tablets ( 4 ). Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. ( 4 )Description
11 DESCRIPTION Drospirenone and Ethinyl Estradiol Tablets, USP provide an oral contraceptive regimen consisting of 24 brown to reddish brown active film-coated tablets each containing 3 mg of drospirenone, USP and 0.02 mg of ethinyl estradiol, USP and 4 white to off-white inert film-coated tablets. The inactive ingredients in the brown to reddish brown tablets are corn starch, crospovidone, hypromellose, iron oxide red, lactose monohydrate, magnesium stearate, povidone, talc, titanium dioxide. The white to off-white inert film-coated tablets contain anhydrous lactose, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polacrilin potassium, polyethylene glycol, polysorbate 80, titanium dioxide. Drospirenone, USP (6 R ,7 R ,8 R ,9 S ,10 R ,13S,14 S ,15 S ,16 S ,17 S )-1,3’,4’,6,6a,7,8,9,10,11,12,13,14,15,15a,16-hexadecahydro-10,13-dimethylspiro-[17 H -dicyclopropa[6,7:15,16]cyclopenta[a]phenanthrene-17,2’(5’H)-furan]-3,5’(2H)-dione) is a synthetic progestational compound and has a molecular weight of 366.49 and a molecular formula of C 24 H 30 O 3 . Ethinyl estradiol, USP (19-Nor-17α-pregna-1,3,5(10)-trien-20-yne-3, 17-diol) is a synthetic estrogenic compound and has a molecular weight of 296.4 and a molecular formula of C 20 H 24 O 2 . The structural formulas are as follows: Drospirenone, USP Ethinyl Estradiol, USP drospirenone.jpg eestructure
What Is Drospirenone And Ethinyl Estradiol Used For?
1 INDICATIONS AND USAGE Drospirenone and ethinyl estradiol tablets are a combination of drospirenone, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to:
Prevent pregnancy. ( 1.1 ) Treat symptoms of premenstrual dysphoric disorder (PMDD) for females of reproductive potential who choose to use an oral contraceptive for contraception. ( 1.2 ) Treat moderate acne for women at least 14 years old only if the patient desires an oral contraceptive for birth control. ( 1.3 ) 1.1 Oral Contraceptive Drospirenone and ethinyl estradiol tablets are indicated for use by females of reproductive potential to prevent pregnancy. 1.2 Premenstrual Dysphoric Disorder (PMDD) Drospirenone and ethinyl estradiol tablets are also indicated for the treatment of symptoms of premenstrual dysphoric disorder (PMDD) in females of reproductive potential who choose to use an oral contraceptive as their method of contraception. The effectiveness of drospirenone and ethinyl estradiol tablets for PMDD when used for more than three menstrual cycles has not been evaluated. The essential features of PMDD according to the Diagnostic and Statistical Manual-4th edition (DSM-IV) include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD include breast tenderness, headache, joint and muscle pain, bloating and weight gain. In this disorder, these symptoms occur regularly during the luteal phase and remit within a few days following onset of menses; the disturbance markedly interferes with work or school, or with usual social activities and relationships with others. Diagnosis is made by healthcare providers according to DSM-IV criteria, with symptomatology assessed prospectively over at least two menstrual cycles. In making the diagnosis, care should be taken to rule out other cyclical mood disorders. Drospirenone and ethinyl estradiol tablets has not been evaluated for the treatment of premenstrual syndrome (PMS). 1.3 Acne Drospirenone and ethinyl estradiol tablets are indicated for the treatment of moderate acne vulgaris in women at least 14 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche. Drospirenone and ethinyl estradiol tablets should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control.Dosage and Administration
2 DOSAGE AND ADMINISTRATION
Take one tablet daily by mouth at the same time every day. ( 2.1 ) Tablets must be taken in the order directed on the blister pack. ( 2.1 ) 2.1 How to Take Drospirenone and Ethinyl Estradiol Tablets Take one tablet by mouth at the same time every day. The failure rate may increase when pills are missed or taken incorrectly. To achieve maximum contraceptive and PMDD effectiveness, drospirenone and ethinyl estradiol tablets must be taken exactly as directed, in the order directed on the blister pack. Single missed pills should be taken as soon as remembered. 2.2 How to Start Drospirenone and Ethinyl Estradiol Tablets Instruct the patient to begin taking drospirenone and ethinyl estradiol tablets either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start). Day 1 Start During the first cycle of drospirenone and ethinyl estradiol tablets use, instruct the patient to take one brown to reddish brown drospirenone and ethinyl estradiol tablet daily, beginning on Day 1 of her menstrual cycle. (The first day of menstruation is Day 1.) She should take one brown to reddish brown drospirenone and ethinyl estradiol tablet daily for 24 consecutive days, followed by one white to off-white inert tablet daily on Days 25 through 28. Drospirenone and ethinyl estradiol tablets should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Drospirenone and ethinyl estradiol tablets can be taken without regard to meals. If drospirenone and ethinyl estradiol tablets are first taken later than the first day of the menstrual cycle, drospirenone and ethinyl estradiol tablets should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. Sunday Start During the first cycle of drospirenone and ethinyl estradiol tablet use, instruct the patient to take one brown to reddish brown drospirenone and ethinyl estradiol tablet daily, beginning on the first Sunday after the onset of her menstrual period. She should take one brown to reddish brown drospirenone and ethinyl estradiol tablet daily for 24 consecutive days, followed by one white to off-white inert tablet daily on Days 25 through 28. Drospirenone and ethinyl estradiol tablets should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Drospirenone and ethinyl estradiol tablets can be taken without regard to meals. Drospirenone and ethinyl estradiol tablets should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration....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 ( 5.4 )] The most frequent adverse reactions (≥ 2%) in contraception and acne clinical trials were: headache/migraine (6.7%), menstrual irregularities (4.7%), nausea/vomiting (4.2%), breast pain/tenderness (4.0%) and mood changes (2.2%). ( 6.1 ) The most frequent adverse reactions (≥ 2%) in PMDD clinical trials were: menstrual irregularities (24.9%), nausea (15.8%), headache (13.0%), breast tenderness (10.5%), fatigue (4.2%), irritability (2.8%), decreased libido (2.8%), increased weight (2.5%), and affect lability (2.1%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115 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 rates in the clinical trials of another drug and may not reflect the rates observed in practice. Contraception and Acne Clinical Trials The data provided reflect the experience with the use of drospirenone and ethinyl estradiol tablets in the adequate and well-controlled studies for contraception (N=1,056) and for moderate acne vulgaris (N=536). For contraception, a Phase 3, multicenter, multinational, open-label study was conducted to evaluate safety and efficacy up to one year in 1,027 women aged 17 to 36 who took at least one dose of drospirenone and ethinyl estradiol tablets. A second Phase 3 study was a single center, open-label, active-controlled study to evaluate the effect of 7 28-day cycles of drospirenone and ethinyl estradiol tablets on carbohydrate metabolism, lipids and hemostasis in 29 women aged 18 to 35. For acne, two multicenter, double-blind, randomized, placebo-controlled studies, in 536 women aged 14 to 45 with moderate acne vulgaris who took at least one dose of drospirenone and ethinyl estradiol tablets, evaluated the safety and efficacy during up to 6 cycles. The adverse reactions seen across the 2 indications overlapped, and are reported using the frequencies from the pooled dataset. The most common adverse reactions (≥ 2% of users) were: headache/migraine (6.7%), menstrual irregularities (including vaginal hemorrhage [primarily spotting] and metrorrhagia (4.7%), nausea/vomiting (4.2%), breast pain/tenderness (4%) and mood changes (mood swings, depression, depressed mood and affect lability) (2.2%). PMDD Clinical Trials Safety data from trials for the indication of PMDD are reported separately due to differences in study design and setting in the Contraception and Acne studies as compared to the PMDD clinical program. Two (one parallel and one crossover designed) multicenter, double-blind, randomized, placebo-controlled trials for the secondary indication of treating the symptoms of PMDD evaluated safety and efficacy of drospirenone and ethinyl estradiol tablets during up to 3 cycles among 285 women aged 18–42, diagnosed with PMDD and who took at least one dose of drospirenone and ethinyl estradiol tablets. Common adverse reactions (≥ 2% of users) were: menstrual irregularities (including vaginal hemorrhage [primarily spotting] and metrorrhagia) (24.9%), nausea (15.8%), headache (13.0%), breast tenderness (10.5%), fatigue (4.2%), irritability (2.8%), decreased libido (2.8%), increased weight (2.5%), and affect lability (2.1%). Adverse Reactions (≥1%) Leading to Study Discontinuation: Contraception Clinical Trials Of 1,056 women, 6.6% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reactions leading to discontinuation were headache/migraine (1.6%) and nausea/vomiting...Drug Interactions
7 DRUG INTERACTIONS Consult the labeling of all 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 (for example, CYP3A4) may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up 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 diminishing the efficacy of COCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease 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, rifampin, topiramate and products containing St. John’s wort. Interactions between oral 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. Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin and certain COCs containing EE increase AUC values for EE by approximately 20%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. Concomitant administration of moderate or strong CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g., clarithromycin, erythromycin), diltiazem, and grapefruit juice can increase the plasma concentrations of the estrogen or the progestin or both. In a clinical drug-drug interaction study conducted in premenopausal women, once daily co-administration of DRSP 3 mg/EE 0.02 mg containing tablets with strong CYP3A4 inhibitor, ketoconazole 200 mg twice daily for 10 days resulted in a moderate increase of DRSP systemic exposure. The exposure of EE was increased mildly [see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 )] . 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 progestin have been noted in some cases of co-administration with HIV/HCV 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. 7.2 Effects of Combined...
Contraindications
4 CONTRAINDICATIONS Drospirenone and ethinyl estradiol tablets are contraindicated in females who are known to have or develop the following conditions:
Renal impairment Adrenal insufficiency A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: o Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions ( 5.1 )] o Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions ( 5.1 )] o Have cerebrovascular disease [see Warnings and Precautions ( 5.1 )] o Have coronary artery disease [see Warnings and Precautions ( 5.1 )] o 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 )] o Have inherited or acquired hypercoagulopathies [see Warnings and Precautions ( 5.1 )] o Have uncontrolled hypertension [see Warnings and Precautions ( 5.6 )] o Have diabetes mellitus with vascular disease [see Warnings and Precautions ( 5.8 )] o Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 [see Warnings and Precautions ( 5.9 )] Undiagnosed abnormal uterine bleeding [see Warnings and Precautions ( 5.10 )] Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions ( 5.3 )] Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions ( 5.4 ) and Use in Specific Populations ( 8.7 )] 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 ( 5.5 ) and Drug Interactions ( 7.3 )]. Renal impairment ( 4 ) Adrenal insufficiency ( 4 ) A high risk of arterial or venous thrombotic diseases ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Breast cancer ( 4 ) Liver tumors or liver...Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, drospirenone and ethinyl estradiol tablets 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 CHCs 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. Data Human Data A retrospective database study of women in Norway, that included 44,734 pregnancies of which 368 were women who inadvertently took DRSP/EE during the first trimester of a pregnancy, found there were no adverse effects on pre-term birth, small for gestational age, or birth weight Z-scores. Post-marketing adverse event data on the use of drospirenone and ethinyl estradiol tablets in pregnant women suggest that frequencies of miscarriage and congenital anomalies were not higher than the estimated background risk in the general population.
Overdosage
10 OVERDOSAGE There have been no reports of serious ill effects from overdose, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea. DRSP is a spironolactone analogue which has anti-mineralocorticoid properties. Serum concentration of potassium and sodium, and evidence of metabolic acidosis, should be monitored in cases of overdose.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Drospirenone and Ethinyl Estradiol Tablets, USP 3 mg/0.02 mg are available as follows: NDC 68462-720-29 1 carton containing 3 individual pouches. Each pouch contains 1 blister of 28 tablets. Each blister contains 28 film-coated tablets in the following order:
24 round, brown to reddish brown film-coated tablets, each containing 3 mg drospirenone, USP and 0.02 mg ethinyl estradiol, USP debossed with “E3” on one side and unscored on the other., 4 round, white to off-white film-coated inert tablets, debossed with “E6” on one side and unscored on the other. 16.2 Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°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.