Ethinyl Estradiol / Levonorgestrel

Ethinyl estradiol / levonorgestrel is a combined hormonal contraceptive used to prevent pregnancy across several products and formulations.

• Amethyst tablets are indicated to prevent pregnancy in women who choose oral contraceptives as their method of contraception
• Dolishale tablets are indicated to prevent pregnancy in women who choose oral contraceptives as their method of contraception
• Levonorgestrel and Ethinyl Estradiol tablets are indicated to prevent pregnancy in women who choose oral contraceptives as their method of contraception
• Twirla (skin patch) is indicated as a contraceptive method specifically for women of reproductive potential with a BMI below 30 kg/m²; its effectiveness is reduced in women with a BMI of 25 to less than 30 kg/m², and it is contraindicated in women with a BMI of 30 or higher

This medication combines a synthetic estrogen (ethinyl estradiol) and a synthetic progestin (levonorgestrel) to prevent pregnancy through several complementary actions. The primary effect is suppression of ovulation — the hormones signal the brain to stop triggering egg release. The medication also thickens the cervical mucus, making it much harder for sperm to enter the uterus, and alters the uterine lining to make implantation less likely.

The way you take this medication depends on the specific product prescribed. Oral tablets (Amethyst, Dolishale, and Levonorgestrel and Ethinyl Estradiol) are taken once daily by mouth at the same time each day — some products are taken continuously without breaks, while extended-cycle versions follow a longer scheduled cycle. Twirla is applied as a new skin patch once a week for three weeks, followed by one patch-free week, repeating every 28 days.

• Take oral tablets at the same time every day — consistency matters for effectiveness
• For Twirla, never go more than 7 days without a patch between cycles
• If you are just starting, a backup contraceptive method may be needed for the first 7 days depending on when you start — check your specific product labeling
• If you miss doses or a patch falls off, follow the instructions in your product's patient labeling and contact your prescriber if unsure

The most commonly reported side effects across products in this class include:

• Headaches and migraines
• Nausea or vomiting
• Irregular or heavy vaginal bleeding, especially in the first few months
• Acne
• Painful periods (dysmenorrhea)
• Weight gain
• Mood changes, depression, or anxiety
• Breast tenderness or discomfort

More serious reactions — including blood clots, liver problems, high blood pressure, or severe depression — require prompt medical attention. Stop taking the medication and contact your doctor or emergency services if you experience chest pain, sudden severe headache, vision changes, leg swelling or pain, or yellowing of the skin or eyes.

Blood clot risk is the most critical concern. Combined hormonal contraceptives increase the risk of venous blood clots (deep vein thrombosis and pulmonary embolism) and arterial events (heart attack and stroke). This risk is significantly higher in women who smoke — particularly those over 35 — and in women with high blood pressure, obesity, diabetes, or inherited clotting conditions. The medication should be stopped at least 4 weeks before major surgery and not restarted until 2 weeks after recovery. Women should not start it until at least 4 weeks after giving birth if not breastfeeding.

• Smoking combined with use of these contraceptives greatly raises the risk of heart attack and stroke, especially in women over 35 — this combination is contraindicated
• Blood pressure should be monitored regularly; stop the medication if it rises significantly
• Liver problems, including elevated liver enzymes, hepatic adenomas (benign liver tumors), and jaundice, are possible — stop the medication if jaundice develops
• Women with high triglycerides may have increased levels on this medication, raising the risk of pancreatitis (pancreas inflammation)
• Depression may worsen; women with a history of depression should be closely monitored
• Certain hepatitis C drug combinations must not be taken at the same time due to the risk of dangerous liver enzyme elevations
• Twirla is contraindicated in women with a BMI of 30 or higher due to reduced effectiveness and increased clot risk

Several medications and substances can interact with ethinyl estradiol / levonorgestrel, either reducing its contraceptive effectiveness or raising the risk of side effects.

• Enzyme inducers (e.g., carbamazepine, phenytoin, rifampin, barbiturates, topiramate, oxcarbazepine, St. John's wort) — lower hormone levels and can reduce contraceptive protection; use a backup method and continue it for 28 days after stopping the interacting drug
• Colesevelam (cholesterol-lowering agent) — reduces estrogen absorption; take at least 4 hours apart
• Certain HIV/HCV antivirals — some (e.g., nelfinavir, ritonavir, nevirapine) lower hormone levels, while others (e.g., atazanavir/ritonavir, etravirine) raise them; discuss with your prescriber
• Hepatitis C combination regimens containing ombitasvir/paritaprevir/ritonavir or glecaprevir/pibrentasvir — must not be used at the same time; can cause serious liver enzyme elevations
• Lamotrigine (seizure medication) — this contraceptive can lower lamotrigine levels, potentially reducing seizure control; dose adjustment may be needed
• Thyroid or corticosteroid replacement therapies — doses of these medications may need to be increased while using this contraceptive
• Atorvastatin, rosuvastatin, and certain antifungals (itraconazole, fluconazole, ketoconazole, voriconazole) — may increase hormone exposure
• Grapefruit juice — may increase estrogen and/or progestin levels

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Women over 35 who smoke must not use combined hormonal contraceptives — the risk of heart attack and stroke is too high
• Do not use if you have a history of blood clots (deep vein thrombosis, pulmonary embolism), stroke, coronary artery disease, or certain heart rhythm problems
• Do not use if you have uncontrolled high blood pressure or high blood pressure with vascular complications
• Do not use if you have migraines with aura; women over 35 with any type of migraine should also avoid these contraceptives
• Do not use during pregnancy; stop the medication and tell your prescriber if you become pregnant
• If breastfeeding, discuss alternatives — this medication can reduce milk production at any stage of breastfeeding
• Do not use if you have active liver disease, liver tumors (benign or malignant), or severe cirrhosis
• Do not use if you have a current or prior diagnosis of breast cancer
• For Twirla: women with a BMI of 30 or higher must not use it; those with a BMI of 25 to under 30 should be aware of reduced effectiveness
• Certain diabetic women (over 35, or with complications such as kidney, eye, or nerve disease) should not use these contraceptives — discuss with your prescriber
• Tell your prescriber about all medications, supplements, and herbal products you take before starting
• This medication is not for use before the first menstrual period (before menarche) or after menopause

Taking too much of this medication may cause nausea, vomiting, and drowsiness or fatigue. Withdrawal bleeding (an early period-like bleed) may also occur in females. There is no specific antidote; treatment focuses on managing symptoms. If you suspect an overdose, contact a poison control center or seek medical care.

This medication works by suppressing the hormonal signals (gonadotropins) that trigger ovulation, effectively preventing egg release. Studies with Twirla showed that approximately 80% of users had progesterone levels consistent with ovulation suppression. Beyond stopping ovulation, the hormones also create cervical mucus that is thicker and harder for sperm to penetrate, and alter the uterine lining to reduce the likelihood of implantation.

After oral administration, levonorgestrel is rapidly and almost completely absorbed (bioavailability close to 100%) and bypasses first-pass metabolism in the liver. Ethinyl estradiol is also quickly absorbed from the gut, but is partially broken down during its first pass through the gut wall and liver, so only about 38–48% reaches the bloodstream. Both hormones reach peak blood levels within about 1.5 hours of a dose. Levonorgestrel is primarily cleared by the kidneys (40–68% in urine) and to a lesser extent in stool, with a half-life of roughly 36 hours at steady state. Ethinyl estradiol has a shorter half-life of about 18 hours and is metabolized mainly by liver enzymes (CYP3A4), then excreted in urine and stool.

and Disposal Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted 15°C to 30°C (59°F to 86°F) . Store in original unopened pouch.