Ethinyl Estradiol and Levonorgestrel - An Overview

Overview:

Levonorgestrel and Ethinyl estradiol combined pills are used to prevent pregnancy by stopping the development of a woman's egg each month. This prevents the egg from being fertilized by sperm. However, no birth control method guarantees 100 percent effectiveness. Methods like surgery for sterilization or abstaining from sex are more reliable than birth control pills. It is important to discuss birth control options with a doctor. These pills do not protect against HIV or other sexually transmitted diseases. They also cannot be used as emergency contraception after having unprotected sex. A person will need a doctor's prescription to get these pills. This medication is available as tablets or chewable tablets. The United States Food and Drug Administration approved Levonorgestrel and Ethinyl estradiol in May 2003.

Drug Group:

Levonorgestrel and Ethinyl estradiol is a combination birth control pill used to prevent pregnancy. It contains two hormones: Levonorgestrel, a type of progestin, and Ethinyl Estradiol, a type of estrogen.

Available Doses and Dosage Forms:

One tablet daily for 28 days in a row:

• First 21 days: One white active tablet each day.

• Next 7 days: One peach inactive tablet each day.

For Patients:

What Is an Oral Contraceptive?

A pill that is used to prevent pregnancy by stopping the release of eggs from the ovaries is known as an oral contraceptive pill. It usually contains two hormones: estrogen and progestin. It is also known as a birth control pill.

How Do Ethinyl Estradiol and Levonorgestrel Work?

The combination of Levonorgestrel and Ethinyl estradiol is used to prevent pregnancy. It works by preventing a woman's egg from maturing each month so it cannot be fertilized by sperm.

What Is the Dosage of Ethinyl Estradiol and Levonorgestrel?

Levonorgestrel and Ethinyl estradiol are available in various forms that can be applied to the skin or taken orally:

• Oral tablets (0.15 mg (milligram)/0.03 mg).

• Oral tablets (0.09 mg/0.02 mg).

• Oral tablets (0.1 mg/0.02 mg).

• Oral tablets (0.05 mg/0.03 mg; 0.75 mg/0.04 mg; 0.125 mg/0.03 mg).

• Oral tablets (0.15 mg/0.03 mg) plus Ethinyl estradiol tablets (0.01 mg).

• Oral tablets (0.1 mg/0.02 mg) plus Ethinyl estradiol tablets (0.01 mg).

• Oral tablets (0.15 mg/0.02 mg; 0.15 mg/0.025 mg; 0.15 mg/0.03 mg) plus Ethinyl Estradiol tablets (0.01 mg).

• The transdermal patch delivers 120 mcg (microgram)/day of Levonorgestrel and 30 mcg/day of Ethinyl Estradiol.

What Are the Things to Inform the Doctor Before Taking Ethinyl Estradiol and Levonorgestrel?

• It is crucial to take this medication exactly as the doctor instructs. Do not take more or use it more frequently or longer than prescribed.

• Follow the patient instructions that come with this medicine carefully and ask the doctor or pharmacist if there are any questions.

• When starting to take this medicine, it takes at least seven days for it to become effective in preventing pregnancy. Use a backup method of birth control, like condoms, spermicide, or a diaphragm, during the first seven days.

• Take the pill at the same time every day. It is most effective when less than 24 hours pass between doses.

• Do not skip or delay a dose by more than 24 hours, as this increases the risk of pregnancy. If a person misses a dose, they should ask the doctor for advice on remembering to take the pills or using another birth control method.

• The patient might feel nauseous, especially in the first few months of taking the pill. If the nausea persists, contact the doctor.

• If a person vomits or has diarrhea after taking the pill, use another form of birth control until informing the doctor.

How Is Ethinyl Estradiol and Levonorgestrel Administered?

An individual can take Levonorgestrel and Ethinyl estradiol tablets in two ways:

• Swallow the tablet whole on an empty stomach.

• Chew the tablet and immediately swallow it with a full glass (240 mL (milliliter)) of water on an empty stomach.

• To ensure the birth control pills work effectively, take them exactly as instructed: One tablet orally at the same time every day, without missing any doses. Missing doses or taking them incorrectly can reduce their effectiveness.

Starting the Tablets:

• If a person is not currently using any hormonal contraception, they should start day one by taking their first tablet on the first day of their period (on an empty stomach).

• Continue taking one tablet at the same time every day.

• Start each new 28-day pack on the same day of the week as the first pack (the day after the last tablet).

• Use an additional non-hormonal contraceptive method (like condoms) for the first seven days of taking the tablets.

Switching from Another Contraceptive Method:

• Combined Oral Contraceptive (COC): Start on the day an individual would begin a new pack of their previous COC.

• Transdermal System (Patch): Start on the day using the next patch application would be due.

• Vaginal Ring: Start on the day using the next ring insertion would be due.

• Injection: Start on the day when the next injection would be due.

• Intrauterine Device (IUD): Start on the day of removal.

• Implant: Start on the day of removal.

What Are the Side Effects of Ethinyl Estradiol and Levonorgestrel?

Serious Side Effects:

The serious side effects of Combined hormonal contraceptives (CHCs) includes:

• Serious heart problems.

• Blood clotting issues.

• Liver problems.

• High blood pressure.

• Gallbladder problems.

• Issues with blood sugar and fat metabolism.

• Headaches.

• Irregular bleeding and missed periods.

• Depression.

• Cervical cancer.

• Effects on blood-binding proteins.

• Hereditary angioedema.

• Skin discoloration.

• Liver enzyme issues with certain Hepatitis C treatments.

Common Side Effects:

Common side effects associated with the use of oral CHCs include:

• Headache.

• Stomach pain.

• Nausea.

• Irregular menstrual bleeding.

• Vaginal yeast infections and pain.

• Acne.

• Vaginal inflammation (vaginitis).

Additional Side Effects:

Other side effects reported include:

• Difficulty wearing contact lenses and changes in the shape of the cornea.

• Abdominal bloating and vomiting.

• Swelling and fluid retention.

• Cholestatic jaundice (a type of liver disease).

• Changes in sex drive and mood changes.

• Missed periods, breast tenderness, breast pain, breast enlargement, increased cervical mucus, changes in menstrual flow, and unexpected bleeding.

• Acne and melasma (skin discoloration).

• Budd-Chiari syndrome (a liver condition) and worsening of varicose veins.

Missed Dose:

• If someone misses the dose, they should take it as soon as they remember it and follow the dosing instructions provided in the patient information leaflet.

• If someone misses one white active tablet in weeks one, two, or three, they should take the missed tablet as soon as they remember, even if it means taking two tablets in one day.

• Continue taking one tablet each day until the pack is completed.

• If a person misses two white active tablets in week one or week two, they should take two tablets as soon as they remember.

• Take two tablets the following day as well (a total of four tablets over two days).

• Continue taking one tablet each day until they finish the pack.

• Use additional non-hormonal contraception (like condoms) if a person has sex within seven days after missing the tablets.

• If the person misses two white active tablets in week three or three or more active tablets in a row in weeks one, two, or three, they should throw out the current pack and start a new one right away.

• Use additional non-hormonal contraception (like condoms) if having sex within seven days after missing the tablets.

• If they miss one or more peach (inactive) tablets in the fourth week, they should throw away the missed inactive tablets.

• Continue taking one tablet each day until the pack is empty.

• No need for backup contraception, but start the next pack on time.

Overdose:

Taking too much of Levonorgestrel and Ethinyl estradiol tablets may cause nausea and vaginal bleeding in women.

Storage:

Keep the product in a controlled room between 20°C (degrees Celsius) and 25°C (68°F (degrees Fahrenheit) and 77°F). Keep out of direct sunlight and extreme heat.

For Doctors:

Indication:

Levonorgestrel and Ethinyl estradiol tablets are a form of birth control meant for women to prevent pregnancy.

Dosing Considerations:

A pack of Levonorgestrel and Ethinyl estradiol Tablets contains 28 tablets:

• 21 Active Tablets: These are white, round, and have "30" on one side and "L2" on the other. Each active tablet contains 0.1 mg of Levonorgestrel and 0.02 mg of Ethinyl Estradiol.

• Seven Inactive (placebo) Tablets: These are peach-colored, round, and have "1" on one side and "L2" on the other.

What Are the Pharmacological Aspects of Ethinyl Estradiol and Levonorgestrel?

• Pharmacodynamics: No specific studies have been conducted on how LNG/EE Tablets affect the body.

• Mechanism of Action: CHCs (combination hormonal contraceptives) reduce the chance of pregnancy mainly by preventing ovulation.

• Pharmacokinetics:

• Absorption: The exact bioavailability of Levonorgestrel and Ethinyl estradiol tablets in humans has not been specifically studied. However, it is known that Levonorgestrel is fully absorbed when taken orally, with a bioavailability of about 100 percent, as it bypasses the first-pass metabolism. Ethinyl estradiol is also quickly absorbed, but its bioavailability ranges from 38 to 48 percent due to metabolism in the gut and liver. Levonorgestrel binds more to sex hormone-binding globulin (SHBG) due to increased SHBG levels from daily Ethinyl estradiol intake.

• Elimination:

  • Metabolism: Levonorgestrel undergoes reduction and hydroxylation, followed by conjugation. Its metabolites are mainly sulfates, with excretion occurring predominantly as glucuronides. Individual differences in metabolic clearance rates result in varied Levonorgestrel levels among users. Ethinyl estradiol is metabolized by liver enzymes (CYP3A4) into a 2-hydroxy metabolite, which is further processed before excretion. The variation in enzyme levels among individuals accounts for different metabolism rates. It is excreted in urine and feces as conjugates and undergoes enterohepatic circulation.

  • Excretion: The elimination half-life of Levonorgestrel is about 36 ± 13 hours, with excretion mainly via urine (40 to 68 percent) and feces (16 to 48 percent). The half-life of Ethinyl estradiol is 18 ± 4.7 hours.

Toxicity: Some studies suggest that using CHCs might raise the risk of cervical cancer or precancerous changes in the cervix. However, it is debated whether these findings are actually due to differences in sexual behavior and other factors.

Clinical Studies:

In a study with Levonorgestrel and Ethinyl estradiol Tablets (LNG/EE Tablets) containing 0.1 mg and 0.02 mg, respectively, 1,477 participants completed 7,720 cycles of use, resulting in five reported pregnancies. This gave an overall pregnancy rate of 0.84 per 100 woman-years. Some participants did not always take the tablets correctly. In 19 percent of the cycles, one or more tablets were missed. These missed tablets or the use of backup contraception in 150 cycles were not included in the calculation of the Pearl Index, which measures contraceptive effectiveness.

What Are the Contraindications of Ethinyl Estradiol and Levonorgestrel?

Levonorgestrel and Ethinyl estradiol Tablets should not be used by women who have any of the following conditions:

High Risk of Blood Clots:

• Women over 35 who smoke.

• Current or past deep vein thrombosis (DVT) or pulmonary embolism (PE).

• Cerebrovascular disease (conditions affecting blood flow to the brain).

• Coronary artery disease (heart disease).

• Heart valve disease or abnormal heart rhythms.

• Blood clotting disorders (inherited or acquired).

• Uncontrolled high blood pressure or high blood pressure with vascular disease.

• Diabetes with complications or diabetes for more than 20 years.

• Severe headaches with neurological symptoms, migraines with aura, or any migraines if over 35.

Cancer:

• Current or past breast cancer or other cancers sensitive to estrogen or progestin

Liver issues:

• Liver tumors, active liver disease, or severe liver cirrhosis

Other conditions:

• Unexplained abnormal vaginal bleeding

• Using certain hepatitis C medications (Ombitasvir/Paritaprevir/Ritonavir, with or without Dasabuvir) due to the risk of liver damage

Warnings and Precautions:

1. Blood Clots and Other Vascular Problems: Before starting Levonorgestrel and Ethinyl estradiol Tablets (LNG/EE Tablets), check if there is a history of blood clotting disorders in the patient or their family. LNG/EE Tablets should not be used by women with a high risk of blood clots. Stop taking LNG/EE Tablets immediately if a blood clot occurs or there is sudden vision loss or eye problems, as these could be signs of a retinal blood clot.

2. Major Surgery: Discontinue LNG/EE Tablets before and after major surgery. If a person needs to be immobile for a long period or is having major surgery, stop taking the tablets at least four weeks before and for two weeks after the procedure.

3. Postpartum Use: Start taking LNG/EE Tablets no earlier than four weeks after delivery if the person is not breastfeeding, as the risk of blood clots decreases after the third postpartum week.

4. Arterial Events: LNG/EE Tablets increase the risk of heart attacks and strokes, especially in women over 35, smokers, and those with high blood pressure, high cholesterol, diabetes, or obesity.

5. Venous Events: LNG/EE Tablets increase the risk of blood clots in the veins, like deep vein thrombosis and pulmonary embolism, especially during the first year of use or after restarting the tablets after a break of four weeks or more. The risk of blood clots is higher during pregnancy and postpartum.

6. Liver Disease: Do not use LNG/EE Tablets if someone has acute viral hepatitis or severe liver cirrhosis. If jaundice (yellowing of the skin or eyes) occurs, stop taking the tablets and get the liver checked. LNG/EE Tablets should not be used if a person has or has had liver tumors, as they increase the risk of liver adenomas, which can rupture and cause severe bleeding. Long-term use of these tablets may slightly increase the risk of liver cancer.

7. High Blood Pressure: LNG/EE tablets are not recommended for women with uncontrolled high blood pressure or high blood pressure with vascular disease. Blood pressure should be monitored regularly, and the tablets should be stopped if blood pressure rises significantly.

8. Age-Related Considerations: The risk of heart disease and its risk factors increase with age. Conditions like smoking and migraines that are not problematic in younger women may be a concern for women over 35 using LNG/EE tablets. Be cautious with women over 35 who have high blood pressure, diabetes, high cholesterol, or obesity.

9. Gallbladder Disease: Using LNG/EE tablets may increase the risk of gallbladder disease or worsen existing conditions. Women with a history of pregnancy-related gallbladder issues may be at higher risk.

10. Effects on Blood Sugar and Lipids: LNG/EE tablets should not be used by diabetic women over 35 or those with diabetes complications. They may reduce glucose tolerance, so monitor diabetic patients carefully. Women with uncontrolled high cholesterol should consider other contraceptives. LNG/EE tablets can increase triglycerides, raising the risk of pancreatitis.

11. Headaches: LNG/EE tablets should not be used by women with migraines or migraines with aura. If new or severe headaches develop, stop taking the tablets and seek evaluation.

12. Irregular Bleeding and Missed Periods: Some women may experience unexpected bleeding, especially in the first three months. If it continues or starts after regular cycles, check for pregnancy or other causes. If a person misses a period, consider pregnancy, especially if they missed doses. If they miss two consecutive periods, get checked for pregnancy.

13. Depression: Monitor women with a history of depression. If depression worsens, stop using LNG/EE tablets.

14. Cervical Cancer: Some studies suggest a link between LNG/EE tablets and increased risk of cervical cancer, though this may be influenced by other factors like sexual behavior.

15. Effect on Binding Proteins: The estrogen in LNG/EE tablets may increase levels of certain blood proteins, possibly requiring adjustments in thyroid or cortisol replacement therapies.

16. Hereditary Angioedema: Estrogens in LNG/EE tablets can trigger or worsen hereditary angioedema symptoms.

17. Chloasma: LNG/EE tablets may cause skin discoloration, especially in women with a history of this condition during pregnancy. Such women should avoid sun or UV exposure while taking tablets.

18. Risk of Liver Enzyme Elevations with Certain Hepatitis C Treatments: Using LNG/EE tablets with Hepatitis C medications can significantly raise liver enzyme levels. Discontinue LNG/EE tablets before starting Hepatitis C treatment and wait at least two weeks after finishing the treatment before restarting the tablets.

What Are the Drug Interactions of Ethinyl Estradiol and Levonorgestrel?

Certain drugs can affect the effectiveness and safety of Levonorgestrel and Ethinyl estradiol tablets (LNG/EE tablets). Drugs that lower CHC effectiveness include enzyme inducers like Rifampin, Efavirenz, and Nevirapine, requiring backup contraception. Colesevelam should be taken four hours apart from CHCs. Drugs like Atorvastatin and CYP3A inhibitors (e.g., Itraconazole) can increase estrogen levels. HIV (Human Immunodeficiency Virus) or HCV (hepatitis C virus) protease inhibitors can either increase or decrease hormone levels. CHCs can lower Lamotrigine effectiveness and may require dose adjustments for thyroid or cortisol replacement therapy. CHCs may also affect lab test results and should not be used with certain Hepatitis C treatments.

Specific Considerations:

• Pregnancy: LNG/EE tablets should not be used during pregnancy. Studies show no increased risk of birth defects from CHC use before conception or early in pregnancy.

• Lactation: Contraceptive hormones can be found in breast milk and may reduce milk production. Nursing mothers should consider other contraception methods until they stop breastfeeding. Small amounts of these hormones in milk may cause jaundice or breast enlargement in infants, and using CHCs postpartum may reduce milk quality and quantity.

• Pediatric Use: LNG/EE tablets are safe and effective for females of reproductive age, including teenagers. They are not intended for use before a girl's first menstrual period.

• Geriatric Use: LNG/EE tablets are not for use in postmenopausal women and have not been studied in this group.

• Hepatic Impairment: Women with liver issues may not metabolize steroid hormones well, possibly requiring discontinuation of LNG/EE tablets until liver function normalizes.

• Body Mass Index (BMI): There is no data on how LNG/EE tablets' safety and effectiveness vary with different BMI levels.