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Rarely, very serious side effects have occurred when estrogen-only and combination hormone replacement therapies (estrogen and progestin HRT) are used after menopause. Discuss the risks and benefits of hormone treatment and your personal health history with your doctor. Combination HRT should not be used to prevent heart disease or dementia. Combination HRT may rarely cause serious problems from blood clots (such as heart attack, stroke, blood clots in the lungs or legs), dementia, and breast cancer. The risk for stroke and breast cancer increases with age, especially for women older than 75. Estrogens may also increase the risk of cancer of the ovaries. Some of these risks appear to depend on the length of time this drug is used and the amount of estrogen per dose. This medication should be used for the shortest possible length of time at the lowest effective dose, so you can obtain the benefits and minimize the chance of serious side effects from long-term treatment. Discuss the details with your doctor and check with him/her regularly (such as every 3-6 months) to see if you still need to take this medication. If you use this drug for an extended time, you should have a complete physical exam at regular intervals (such as once a year) or as directed by your doctor. See Notes section.

Dizziness, lightheadedness, headache, stomach upset, bloating, irritability, changes in sleep patterns, nausea, weight changes, increased/decreased interest in sex, change in vaginal discharge, or breast tenderness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly. Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects. Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as depression, memory loss), breast lumps, nipple discharge, swelling of the hands/feet, unusual vaginal bleeding (such as spotting, breakthrough bleeding, prolonged/returning bleeding), yellowing eyes/skin, stomach/abdominal pain, worsening of a seizure condition, muscle weakness, signs of worsening diabetes control (such as increased thirst and urination), symptoms of a high potassium blood level (such as muscle weakness, slow/irregular heartbeat). This medication may rarely cause serious (sometimes fatal) problems from blood clots (such as heart attack, stroke, blood clots in the lungs or legs). Get medical help right away if you have: pain/swelling/warmth in the groin/calf, shortness of breath/rapid breathing, chest/jaw/left arm pain, unusual sweating, sudden dizziness/fainting, confusion, trouble speaking, weakness on one side of the body, sudden vision changes, sudden/severe headaches. A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing. This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. In the US - Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Some products that may interact with this drug are: aromatase inhibitors (such as anastrozole, exemestane), atazanavir/cobicistat, corticosteroids (such as prednisone), fezolinetant, ospemifene, raloxifene, tamoxifen, tizanidine, tranexamic acid, warfarin. Drospirenone may raise your potassium blood level. Tell your doctor if you are regularly taking other drugs/products that can also raise your potassium level (including aliskiren, ACE inhibitors such as enalapril/lisinopril, angiotensin receptor blockers such as losartan/valsartan, heparin, NSAIDs such as ibuprofen/naproxen, potassium-sparing "water pills"/diuretics such as eplerenone/spironolactone/triamterene). Other medications can affect the removal of estrogen from your body, which may affect how estrogen works. Examples include azole antifungals (such as itraconazole), macrolide antibiotics (such as erythromycin), rifamycins (such as rifabutin), St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin), among others. This medication may interfere with certain lab tests, possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.