MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) is indicated for use by females of reproductive potential to prevent pregnancy.
Contraindications
MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) is 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: o Smoke, if over age 35 [see BOXED WARNING and WARNINGS (1)]. o Have current or history of deep vein thrombosis or pulmonary embolism [see WARNINGS (1)]. o Have cerebrovascular disease [see WARNINGS (1)]. o Have coronary artery disease [see WARNINGS (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 (1)]. o Have inherited or acquired hypercoagulopathies [ see WARNING S (1)]. o Have uncontrolled hypertension or hypertension with vascular disease [see WARNINGS (3)]. o 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 (7)]. o Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see WARNINGS (8)].
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 (5)].
1. Thromboembolic Disorders and Other Vascular Conditions
Stop MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) if an arterial or venous thrombotic/thromboembolic event occurs.
Stop MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.
Discontinue MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) during prolonged immobilization. If feasible, stop MARLISSA ® at least four weeks before and through two weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism.
Start MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) no earlier than four weeks after delivery in females who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week.
Before starting MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases (see CONTRAINDICATIONS ). Arterial Events COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (> 35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity. MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) is contraindicated in women over 35 years of age who smoke (see CONTRAINDICATIONS ). Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. Venous Events Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of COCs (see CONTRAINDICATIONS ). While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman-years. The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. Based on results from a few studies, there is some evidence that this is true for non-oral products as well. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued. Figure 1 shows the risk of developing a VTE for females who are not pregnant and do not use oral contraceptives, for females who use oral contraceptives, for pregnant females, and for females in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 females who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these females will develop a VTE. Figure 1: Likelihood of Developing a VTE Figure1.jpg 2. Liver Disease Elevated Liver Enzymes MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) is contraindicated in females with acute viral hepatitis or severe (decompensated) cirrhosis of liver (see CONTRAINDICATIONS ). Discontinue MARLISSA ® if jaundice develops. Acute liver test abnormalities may necessitate the discontinuation of COC use until the liver tests return to normal and COC causation has been excluded. Liver Tumors MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) is contraindicated in females with benign or malignant liver tumors (see CONTRAINDICATIONS ). COCs increase the risk of hepatic adenomas. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death from abdominal hemorrhage. Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (> 8 years) COC users. The attributable risk of liver cancers in COC users is less than one case per million users. 3. Hypertension MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) is contraindicated in females with uncontrolled hypertension or hypertension with vascular disease (see CONTRAINDICATIONS ). For all females, including those with well- controlled hypertension, monitor blood pressure at routine visits and stop MARLISSA ® if blood pressure rises significantly. An increase in blood pressure has been reported in females using COCs, and this increase is more likely in older women with extended duration of use. The effect of COCs on blood pressure may vary according to the progestin in the COC. 4. Age-related Considerations The risk for cardiovascular disease and prevalence of risk factors for cardiovascular disease increase with age. Certain conditions, such as smoking and migraine headache without aura, that do not contraindicate COC use in younger females, are contraindications to use in women over 35 years of age [see CONTRAINDICATIONS and WARNINGS (1)]. Consider the presence of underlying risk factors that may increase the risk of cardiovascular disease or VTE, particularly before initiating a COC for women over 35 years, such as:
Hypertension
Diabetes
Dyslipidemia
Obesity 5. 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 MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir (see CONTRAINDICATIONS ). MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen. 6. Gallbladder Disease Studies suggest an increased risk of developing gallbladder disease among COC users. Use of COCs may also worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Females with a history of pregnancy-related cholestasis may be at an increased risk for COC- related cholestasis. 7. Adverse Carbohydrate and Lipid Metabolic Effects Hyperglycemia MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) is contraindicated in diabetic women over age 35, or females who have diabetes with hypertension, nephropathy, retinopathy, neuropathy, other vascular disease, or females with diabetes of > 20 years duration (see CONTRAINDICATIONS ). MARLISSA ® may decrease glucose tolerance. Carefully monitor prediabetic and diabetic females who are using MARLISSA ® . Dyslipidemia Consider alternative contraception for females with uncontrolled dyslipidemia. MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) may cause adverse lipid changes. Females with hypertriglyceridemia, or a family history thereof, may have an increase in serum triglyceride concentrations when using MARLISSA ® , which may increase the risk of pancreatitis. 8. Headache MARLISSA ® (levonorgestrel and ethinyl estradiol tablets) is contraindicated in females who have headaches with focal neurological symptoms or have migraine headaches with aura, and in women over age 35 years who have migraine headaches with or without aura (see CONTR
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Adverse reactions
The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:
Serious cardiovascular adverse events [see BOXED WARNING and WARNINGS (1)]
Vascular events [see WARNINGS (1)]
Liver disease [see WARNINGS (2)]
Hypertension [see WARNINGS (3)]
Gallbladder disease [see WARNINGS (6)]
Carbohydrate and lipid effects [see WARNINGS (7)]
Headache [see WARNINGS (8)]
Carcinoma of the cervix [see WARNINGS (11)] Adverse reactions reported by COC users and described elsewhere in the labeling are:
Bleeding irregularities and amenorrhea [see WARNINGS (9)]
Mood changes, including depression [see WARNINGS (10)]
Melasma/chloasma which may persist [see WARNINGS (14)]
Edema/fluid retention [see PRECAUTIONS (2)]
Diminution in lactation when given immediately postpartum [see PRECAUTIONS (7)] Post Marketing 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 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 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 2: 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 reported in patients receiving oral contraceptives and are believed to be drug-related: Breast tenderness, pain, enlargement, secretion; Nausea, vomiting and gastrointestinal symptoms (such as abdominal pain, cramps and bloating); Change in menstrual flow; Temporary infertility after discontinuation of treatment; Change in weight or appetite (increase or decrease); Change in cervical erosion and secretion; Cholestatic jaundice; Rash (allergic); Vaginitis, including candidiasis; Change in corneal curvature (steepening); Intolerance to contact lenses; Mesenteric thrombosis; Decrease in serum folate levels; Exacerbation of systemic lupus erythematosus; Exacerbation of porphyria; Exacerbation of chorea; Aggravation of varicose veins; Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms. The following adverse reactions have been reported in users of oral contraceptives, and the association has been neither confirmed nor refuted: Congenital anomalies; Premenstrual syndrome; Cataracts; Optic neuritis, which may lead to partial or complete loss of vision; Cystitis-like syndrome; Nervousness; Dizziness; Hirsutism; Loss of scalp hair; Erythema multiforme; Erythema nodosum; Hemorrhagic eruption; Impaired renal function; Hemolytic uremic syndrome; Budd-Chiari syndrome; Acne; Changes in libido; Colitis; Sickle-cell disease; Cerebral-vascular disease with mitral valve prolapse; Lupus-like syndromes; Pancreatitis; Dysmenorrhea. Figure-2
Composition
Active ingredients
ETHINYL ESTRADIOL 0.03MG; LEVONORGESTREL 0.15MG
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application ANDA091452.
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.
