Levonorgestrel and Ethinyl Estradiol: FDA label

Vascular risks: Stop if a thrombotic or thromboembolic event occurs. Stop at least 4 weeks before and through 2 weeks after major surgery. Start no earlier than 4 weeks after delivery, in women who are not breastfeeding. Consider cardiovascular risk factors before initiating in all females, particularly those over 35 years. ( 5.1 , 5.5 )
Liver disease: Discontinue if jaundice occurs. ( 5.2 )
Hypertension: If used in women with well-controlled hypertension, monitor blood pressure and stop if blood pressure rises significantly. ( 5.4 )
Gallbladder disease: May cause or worsen gallbladder disease. ( 5.5 )
Adverse carbohydrate and lipid effects: Monitor glucose in prediabetic and diabetic women taking levonorgestrel and ethinyl estradiol. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. ( 5.7 )
Headache: Evaluate significant change in headaches and discontinue if indicated. ( 5.8 )
Uterine bleeding: May cause irregular bleeding or amenorrhea. Evaluate for other causes if symptoms persist. ( 5.9 )

5.1Thromboembolic Disorders and Other Vascular

Conditions

Stop levonorgestrel and ethinyl estradiol if an arterial or venous thrombotic/thromboembolic event occurs.
Stop levonorgestrel and ethinyl estradiol if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.
Discontinue levonorgestrel and ethinyl estradiol during prolonged immobilization. If feasible, stop levonorgestrel and ethinyl estradiol at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism.
Start levonorgestrel and ethinyl estradiol no earlier than 4 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 levonorgestrel and ethinyl estradiol evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Levonorgestrel and ethinyl estradiol is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases [see Contraindications ( 4 )] . 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. Levonorgestrel and ethinyl estradiol is contraindicated in women over 35 years of age who smoke [see Contraindications ( 4 )] . 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 ( 4 )] . 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. 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 * Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY. Use of levonorgestrel and ethinyl estradiol provides women with more hormonal exposure on a yearly basis than conventional monthly COCs containing the same strength synthetic estrogens and progestins (an additional 9 weeks of exposure per year). In the clinical trial, one case of pulmonary embolism was reported. Postmarketing adverse reactions of VTE have been reported in women who used levonorgestrel and ethinyl estradiol. figure1

5.2Liver Disease Elevated Liver Enzymes Levonorgestrel

and ethinyl estradiol is contraindicated in females with acute viral hepatitis or severe (decompensated) cirrhosis of the liver [see Contraindications ( 4 )] . Acute liver test abnormalities may necessitate the discontinuation of levonorgestrel and ethinyl estradiol until the liver tests return to normal and levonorgestrel and ethinyl estradiol causation has been excluded. Discontinue levonorgestrel and ethinyl estradiol if jaundice develops.

Liver Tumors Levonorgestrel and ethinyl estradiol is contraindicated in females with benign and malignant liver tumors [ seeContraindications ( 4 ) ]. 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 through intra-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.

5.3Risk 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 levonorgestrel and ethinyl estradiol. Discontinue levonorgestrel and ethinyl estradiol prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Contraindications ( 4 )].

Levonorgestrel and ethinyl estradiol can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

5.4Hypertension Levonorgestrel

and ethinyl estradiol is contraindicated in females with uncontrolled hypertension or hypertension with vascular disease [see Contraindications ( 4 )]. For all women, including those with well-controlled hypertension, monitor blood pressure at routine visits and stop levonorgestrel and ethinyl estradiol if blood pressure rises significantly. An increase in blood pressure has been reported in females taking COCs, and this increase is more likely in older women and with extended duration of use.

The effect of COCs on blood pressure may vary according to the progestin in the COC.

5.5Age-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 ( 4 ) and Warnings and Precautions ( 5.1 )] . Consider the presence of underlying risk factors that may increase the risk of cardiovascular disease or VTE, particularly before initiating levonorgestrel a

Levonorgestrel and Ethinyl Estradiol

Indications

Contraindications

Two medicines in one question?

Levonorgestrel and Ethinyl Estradiol

Indications

Contraindications

Two medicines in one question?

Warnings and precautions

5.1Thromboembolic Disorders and Other Vascular

5.2Liver Disease Elevated Liver Enzymes Levonorgestrel

5.3Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment

5.4Hypertension Levonorgestrel

5.5Age-related Considerations

Interactions

7.1Effects of Other Drugs on Combined Oral Contraceptives

7.2Effects of Combined Oral Contraceptives on Other Drugs Table

7.3Concomitant Use with Hepatitis C Virus (HCV) Combination

7.4Effect on Laboratory Tests

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trial Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information

At a glance