Drospirenone / Ethinyl Estradiol

Drospirenone / ethinyl estradiol is a combination hormonal contraceptive used for several purposes, depending on the specific product:

• Preventing pregnancy — all products, including Yaz, Yasmin, Nikki, Ocella, Syeda, Loryna, Vestura, Jasmiel, Zumandimine, Lo-Zumandimine, and generics
• Treating moderate acne — approved for women at least 14 years old who also want to use an oral contraceptive for birth control; supported by Yaz, Nikki, Loryna, Vestura, Jasmiel, Lo-Zumandimine, and drospirenone / ethinyl estradiol generics
• Treating symptoms of PMDD (premenstrual dysphoric disorder) — only for those choosing oral contraception; supported by Yaz, Nikki, Loryna, Vestura, Jasmiel, Lo-Zumandimine, and drospirenone / ethinyl estradiol generics; effectiveness beyond three menstrual cycles has not been evaluated for this use

This pill combines two synthetic hormones: drospirenone, a progestin, and ethinyl estradiol, an estrogen. They work primarily by suppressing ovulation — preventing the ovaries from releasing an egg. They may also thicken cervical mucus so sperm cannot pass through as easily, and alter the uterine lining. Drospirenone is unique among progestins in that it has anti-androgenic (blocks male hormone) and anti-mineralocorticoid (mild potassium-retaining, like spironolactone) properties. The anti-androgenic activity may play a role in the improvement of acne, though the exact mechanism for the acne benefit has not been fully established.

Take one tablet by mouth at the same time every day, in the order shown on the blister pack — do not skip or rearrange tablets. You can start either on Day 1 of your menstrual period or on the first Sunday after your period begins, as directed by your prescriber. Missing pills or taking them out of order raises the chance of pregnancy.

• If you miss a single pill, take it as soon as you remember and continue the pack as normal
• Taking the pill with a high-fat meal may slow absorption slightly; always follow any food instructions on your specific product's label
• Follow your prescriber's and pharmacist's instructions for your specific brand, as pack lengths and pill colors vary by product

The most commonly reported side effects include:

• Headache or migraine
• Nausea or vomiting
• Breast pain or tenderness
• Irregular bleeding or spotting, especially in the first few months
• Mood changes, including depressed mood or mood swings
• Fatigue
• Decreased sex drive
• Weight gain

Serious reactions — including blood clots, stroke, liver problems, and severe high blood pressure — are less common but require immediate medical attention. Stop the pill and call your doctor or 911 if you experience sudden chest pain, severe headache, vision changes, or leg pain and swelling.

• Blood clots (venous thromboembolism): This is the most serious risk. Drospirenone-containing pills may have a higher clot risk than pills with some other progestins. Risk is greatest in the first 6 months, and in women who smoke, are obese, or have other risk factors. Stop immediately and get help for chest pain, leg swelling, or sudden vision or speech changes.
• Smoking over age 35: Do not use this medication if you are over 35 and smoke — the risk of heart attack, stroke, and death from blood clots is significantly increased.
• High potassium (hyperkalemia): Drospirenone can raise potassium levels, especially in women taking certain blood pressure or kidney medications. This can be dangerous. Your potassium should be checked during the first treatment cycle if you take such medications.
• High blood pressure: Monitor blood pressure regularly. Stop the pill if blood pressure rises significantly. Do not use if you have uncontrolled high blood pressure.
• Liver problems: Stop the pill if you develop jaundice (yellowing of skin or eyes). Do not use if you have liver disease or liver tumors.
• Depression: Women with a history of depression should be monitored closely; stop the pill if serious depression returns.
• Migraine: New, worsening, or frequent migraines — especially with neurological symptoms — may require stopping the medication.

This medication can interact with several drugs and supplements — always tell your doctor and pharmacist everything you take:

• Seizure medications (phenytoin, carbamazepine, barbiturates, oxcarbazepine, felbamate, topiramate) — can make the pill less effective; use a backup method
• Rifampin (antibiotic) and griseofulvin (antifungal) — reduce pill effectiveness; use a backup method and for 28 days after stopping the enzyme inducer
• St. John's Wort — herbal supplement that can reduce effectiveness and cause breakthrough bleeding
• Ketoconazole, itraconazole, clarithromycin and other strong CYP3A4 inhibitors — can raise drospirenone levels in the blood, increasing high-potassium risk
• ACE inhibitors, potassium-sparing diuretics, NSAIDs, potassium supplements, heparin, aldosterone antagonists — can raise potassium to dangerous levels when combined with drospirenone
• Lamotrigine (seizure medication) — this pill can significantly lower lamotrigine levels, potentially reducing seizure control; dose adjustment may be needed
• Thyroid hormone replacement — this pill raises thyroid-binding proteins; your thyroid hormone dose may need to be increased
• Hepatitis C combination drugs containing ombitasvir/paritaprevir/ritonavir (with or without dasabuvir) — do NOT combine; can cause severe liver enzyme elevations

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

• Do not use if you are over 35 and smoke — risk of fatal cardiovascular events is significantly increased
• Do not use if you have kidney impairment or adrenal insufficiency — drospirenone can cause dangerous potassium buildup
• Do not use if you have liver disease or liver tumors (benign or malignant)
• Do not use if you have or have had breast cancer (which may be hormone-sensitive)
• Do not use if you have a history of blood clots, stroke, or heart attack, or conditions that raise clot risk (e.g., certain heart valve disorders, atrial fibrillation, inherited clotting disorders)
• Do not use if you have uncontrolled high blood pressure or diabetes with blood vessel complications
• Do not use if you have migraines with aura and are over 35, or migraines with focal neurological symptoms at any age
• Do not use during pregnancy
• Use with caution if breastfeeding — the pill can reduce milk production; drospirenone passes into breast milk in small amounts
• Safe for postpubertal adolescents at least 14 years old for acne; not for use before the first menstrual period
• Not studied in or intended for postmenopausal women
• Tell your doctor about any history of depression, gallbladder disease, high triglycerides, or hereditary angioedema

There are no reports of serious harmful effects from taking too much of this medication, even when children have accidentally ingested it. An overdose may cause nausea and, in females, withdrawal bleeding. Because drospirenone can affect potassium levels, a doctor should check potassium, sodium, and acid-base balance if a significant overdose is suspected.

Drospirenone is a progestin with two additional hormone-related properties: it blocks mineralocorticoid receptors (like a mild dose of spironolactone, a water-balancing drug) and has anti-androgenic activity (it counters the effects of testosterone). Ethinyl estradiol, the estrogen component, raises levels of sex hormone-binding globulin (SHBG) and decreases free testosterone circulating in the blood. Together, these effects form the basis of the combination's potential benefit for acne, though the exact relationship between these hormonal changes and acne improvement has not been fully established. More than 90% of study participants showed successful ovulation suppression with this combination.

Both drospirenone and ethinyl estradiol are absorbed quickly after swallowing a tablet, reaching peak blood levels within about 1 to 2 hours. Drospirenone stays active in the body for roughly 30 hours before it is cleared, and it builds up steadily in the blood over about 8 days of daily use. Ethinyl estradiol has a shorter half-life of about 24 hours. Both hormones are broken down mainly by the liver (using an enzyme called CYP3A4) and are excreted in urine and feces as inactive byproducts. Eating a high-fat meal can slow absorption and modestly reduce the amount of ethinyl estradiol the body takes in, but does not significantly affect drospirenone overall.

Store at 25°C (77°F); excursions permitted to 15-30°C (59 - 86°F) .