Vienva (levonorgestrel and ethinyl estradiol tablets, USP) is indicated for use by females of reproductive potential to prevent pregnancy. Limitations of use : The efficacy of levonorgestrel and ethinyl estradiol in women with a body mass index (BMI) of > 35 kg/m 2 has not been adequately evaluated. In a clinical trial with levonorgestrel and ethinyl estradiol tablets, 1,477 subjects had 7,720 cycles of use and a total of 5 pregnancies were reported.
This represents an overall pregnancy rate of 0.84 per 100 woman-years. This rate includes patients who did not take the drug correctly. One or more pills were missed during 1,479 (18.8%) of the 7,870 cycles; thus all tablets were taken during 6,391 (81.2%) of the 7,870 cycles. Of the total 7,870 cycles, a total of 150 cycles were excluded from the calculation of the Pearl index due to the use of backup contraception and/or missing 3 or more consecutive pills.
The mean BMI of the study population was 24 kg/m 2 . Females with a BMI greater than 30 kg/m 2 accounted for 12.1% (n=179) of the study population. Females with a BMI over 35 kg/m 2 accounted for 4.3% (n=63) of the study population.
Contraindications
Combination oral contraceptives should not be used in women with any of the following conditions: Thrombophlebitis or thromboembolic disorders A history of deep-vein thrombophlebitis or thromboembolic disorders Cerebrovascular or coronary artery disease (current or past history) Valvular heart disease with thrombogenic complications Thrombogenic rhythm disorders Hereditary or acquired thrombophilias Prolonged immobilization (especially with major surgery) Diabetes with vascular involvement Headaches with focal neurological symptoms or migrane with aura Women with migrane who are 35 years or older Uncontrolled hypertension Known or suspected carcinoma of the breast or personal history of breast cancer Known or suspected estrogen- or progesterone sensitive malignancy Undiagnosed abnormal vaginal bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Hepatic adenomas or carcinomas, or active liver disease Women who are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for alanine aminotransferase (ALT) elevations (see WARNINGS , RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT).
Warnings and precautions
WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combined 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 levonorgestrel and ethinyl estradiol, are contraindicated in women who are over 35 years of age and smoke.
The use of oral contraceptives is associated with increased risks of several serious conditions including venous and arterial thrombotic and thromboembolic events (such as myocardial infarction, thromboembolism, and stroke), hepatic neoplasia, gallbladder disease, and hypertension, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as certain inherited or acquired thrombophilias, hypertension, hyperlipidemias, obesity, diabetes, and surgery or trauma with increased risk of thrombosis (see CONTRAINDICATIONS ).
Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks. The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher doses of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower doses of both estrogens and progestogens remains to be determined.
Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral-contraceptive users and nonusers.
The attributable risk does provide information about the actual occurrence of a disease in the population. For further information, the reader is referred to a text on epidemiological methods. 1. Thromboembolic Disorders and Other Vascular Problems Cardiovascular and Cerebrovascular Events Use of CHCs increases the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk of these events with CHC use is greater in females with concomitant risk factors: age 35 years and older, smoking, hypertension, dyslipidemia, diabetes, or obesity.
The risk increases with increasing age and with increasing number of cigarettes smoked. Venous Thromboembolism Use of CHCs also increases the risk of VTE, such as deep vein thrombosis and pulmonary embolism. The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman-years. The VTE risk should be considered in the context of relevant subpopulations of females of reproductive potential who are not taking CHCs (see ADVERSE REACTIONS ).
Risk factors for VTE with CHC use include smoking, obesity, family history of VTE, and prolonged immobilization, in addition to other factors that contraindicate use of CHCs (see CONTRAINDICATIONS ). The presence of multiple risk factors for VTE with CHC use may further increase the risk. The risk of VTE is highest during the first year of CHC use and when restarting hormonal contraception after a break of four weeks or longer.
The risk of VTE returns to baseline approximately 3 months after CHC use is discontinued. Postpartum Venous Thromboembolism The risk of VTE is increased during the first six weeks postpartum. The risk is highest up to four weeks postpartum but remains higher than baseline until at least six weeks postpartum. The presence of multiple risk factors for VTE may further increase the risk. Obstetric complications may extend the elevated risk up to 12 weeks postpartum. 2.
Malignant Neoplasms Breast Cancer Levonorgestrel and ethinyl estradiol is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive (see CONTRAINDICATIONS ). Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer.
However, some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use (see ADVERSE REACTIONS ). Cervical Cancer Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia or invasive cervical cancer in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. 3.
Hepatic Neoplasia Benign hepatic adenomas are associated with oral-contraceptive use, although the incidence of these benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use. Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.
Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) oral-contraceptive users. However, these cancers are extremely rare in the U.S. and the attributable risk (the excess incidence) of liver cancers in oral-contraceptive users approaches less than one per million users. 4. Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications such as COCs.
Discontinue levonorgestrel and ethinyl estradiol prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir (see CONTRAINDICATIONS ). Levonorgestrel and ethinyl estradiol can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen. 5. Ocular Lesions There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives that may lead to partial or complete loss of vision.
Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately. 6. Oral-Contraceptive Use Before or During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in infants born to women who have used oral contraceptives prior to pregnancy.
Studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb-reduction defects are concerned, when taken inadvertently during early pregnancy (see CONTRAINDICATIONS ). It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period.
Oral-contraceptive use should be discontinued if pregnancy is confirmed. 7. Gallbladder Disease Combination oral contraceptives may worsen existing gallbladder disease a
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Adverse reactions
An increased risk of the following serious adverse reactions (see WARNINGS section for additional information) has been associated with the use of oral contraceptives: Thromboembolic and thrombotic disorders and other vascular problems (including thrombophlebitis and venous thrombosis with or without pulmonary embolism, mesenteric thrombosis, arterial thromboembolism, myocardial infarction, cerebral hemorrhage, cerebral thrombosis), carcinoma of the reproductive organs and breasts, hepatic neoplasia (including hepatic adenomas or benign liver tumors), ocular lesions (including retinal vascular thrombosis), gallbladder disease, carbohydrate and lipid effects, elevated blood pressure, and headache including migraine.
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 2). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). 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 2: 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 associated with the use of oral CHCs were identified in clinical studies or postmarketing reports.
Because some of these reactions were 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. Common adverse reactions associated with oral CHCs are headache, abdominal pain, nausea, metrorrhagia, vaginal moniliasis and pain, acne, and vaginitis. Additional adverse reactions that have been reported include the following: Eye disorder: intolerance to contact lenses, steepening of corneal curvature Gastrointestinal disorders: Abdominal bloating, vomiting General disorders and administration site conditions: Edema, fluid retention Hepatobiliary disorders: Cholestatic jaundice Pyschiatric disorders: Change in libido, mood changes Reproductive system and breast disorders: Amenorrhea, breast tenderness, breast pain, breast enlargement, increased cervical mucous, change in menstrual flow, unscheduled bleeding Skin and subcutaneous tissue disorders: Acne, melasma Vascular disorders: Budd-Chiari syndrome, aggravation of varicose veins
Composition
Active ingredients
ETHINYL ESTRADIOL 0.02MG; LEVONORGESTREL 0.1MG
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application ANDA201088.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
