This is a combination product contains two medications: drospirenone and estradiol. Drospirenone belongs to the class of medications called progestins. Estradiol belongs to the class of medications called estrogens. This medication is used as an oral hormone replacement therapy.

This medication is used to relieve menopausal symptoms and vaginal symptoms associated with menopause. It should be not be used by women whose only symptom is vaginal dryness. Other medications that can be applied topically (directly to the affected area) are available for vaginal dryness.

This medication is designed for women who have not had a hysterectomy (removal of the uterus or womb). These women require progestin while taking estrogen to prevent complications associated with taking estrogen alone, such as the overgrowth of the uterine lining (endometrial hyperplasia).

Estrogens and progestins are female hormones. They are produced by the body and are necessary for the normal sexual development of the female and for the regulation of the menstrual cycle during the childbearing years. During and after menopause, the ovaries start to produce less of these hormones. A deficiency of estrogen can result in symptoms associated with menopause such as hot flashes, unusual sweating, chills, dryness of the vagina, and sleep disturbances.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

The recommended dose of drospirenone - estradiol is one tablet once daily with or without food. Swallow the tablets whole with a glass of water. Drospirenone - estradiol tablets are to be taken every day; there are no "pill-free" days.

Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important to use this medication exactly as prescribed by your doctor. If you miss a dose, take it as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice. If you miss several tablets you may experience vaginal bleeding or spotting.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children. Do not refrigerate or freeze.

Each round, biconvex, dark pink, film-coated tablet, embossed on one side with the letters "DU" inside a regular hexagon, contains 1 mg of drospirenone and 1 mg of estradiol. Nonmedicinal ingredients: corn starch, hydroxypropyl methylcellulose, ferric oxide pigment, lactose monohydrate, macrogol 6000, magnesium stearate, modified starch, povidone 25 000, talc, and titanium dioxide.

Do not take this medication if you:

• are allergic to drospirenone, estradiol, or any ingredients of this medication
• are breast-feeding
• are or may be pregnant
• are at high risk of developing blood clots
• have a history of known or suspected estrogen-dependent or progestin-dependent tumours, such as breast cancer or endometrial cancer
• have decreased liver function or liver disease with increased levels of liver function enzymes
• have or have had liver tumours
• have classic migraine
• have endometrial hyperplasia (thickening of the inner lining of the uterus)
• have had a hysterectomy (surgical removal of the uterus)
• have or have had a stroke or heart attack or coronary heart disease
• have or have had active blood clotting disorders (e.g., thrombophlebitis, deep vein thrombosis, or pulmonary embolism)
• have partial or complete loss of vision from blood vessel disease of the eyes
• have severe hypertriglyceridemia (high level of fatty acids in the blood)
• have severe kidney disease
• have unusual vaginal bleeding that has not been checked by a doctor

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• abdominal gas, gas pains
• back pain
• bloating
• breakthrough bleeding or spotting
• change in sense of taste
• constipation
• darkening of facial skin
• diarrhea
• dizziness
• general feeling of being unwell
• headache
• hot flashes
• increased appetite
• mood swings
• nausea
• problems wearing contact lenses
• spinning sensation
• trouble sleeping
• unusual hair loss or growth
• vaginal discharge (not bleeding)
• vomiting
• weakness
• weight changes

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• abdominal pain with nausea or vomiting
• acne
• anxiety or nervousness
• breast enlargement that is very painful and uncomfortable
• breast lumps
• breast pain
• decreased libido (sexual desire)
• difficulty breathing
• enlarged fibroids
• fast or irregular heartbeat
• heavy, painful menstrual bleeding
• increase in blood pressure
• migraine headache
• muscle cramps
• painful joints
• pelvic pain
• signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• swelling of feet, hands, and around ankles
• symptoms of a urinary tract infection (e.g., pain when urinating, urinating more often than usual, low back or flank pain)
• tingling or numbness
• trouble concentrating
• unexpected vaginal bleeding
• vaginal itching or discharge
• varicose veins
• visual changes
• weight gain

Stop taking the medication and seek immediate medical attention if any of the following occur:

• signs of an allergic reaction (such as difficulty breathing, hives, rash, swelling of the face or throat)
• signs of blood clots (e.g., coughing up blood; pains in chest, groin, or leg – especially in calf of leg)
• signs of heart attack (e.g., sudden chest pain or pain radiating to back, down arm, jaw; sensation of fullness of the chest; nausea; vomiting; sweating; anxiety)
• signs of stroke (e.g., sudden or severe headache; sudden loss of coordination; vision changes; sudden slurring of speech; or unexplained weakness, numbness, or pain in arm or leg)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Asthma: Fluid build-up caused by the effects of estrogen may cause difficulty breathing and worsening of asthma symptoms. If you have asthma, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Bleeding: If you miss taking several doses of this medication, vaginal bleeding may occur. Also, irregular menstrual bleeding may occur while taking drospirenone - estradiol, especially within the first 6 months of starting this medication. This decreases with time and women may experience no bleeding after using this medication for a while.

Blood clotting disorders: Estrogens, with or without progestins, are associated with an increased risk of blood clots in the lungs (pulmonary embolism) and legs (deep vein thrombosis). This risk also increases with age, a personal or family history of blood clots, smoking, and obesity. The risk of blood clots is also increased if you are immobilized for prolonged periods and with major surgery. If possible, this medication should be stopped 4 weeks before major surgery. Talk about the risk of blood clots with your doctor.

Blood pressure: Women may experience increased blood pressure when using hormone replacement therapy. Ask your doctor how often you should have your blood pressure checked.

Breast and ovarian cancer: Studies indicate an increased risk of breast and ovarian cancer with the use of combined estrogen and progestin therapy. If you have a history of breast cancer, you should not use estrogens. If your family has a history of breast cancer or if you have a history of breast lumps, breast biopsies, or abnormal mammograms, your doctor will monitor your condition closely while you are using estrogens.

Have a mammogram before starting hormone replacement therapy. Have regular breast examinations and become familiar with your breasts so you can let your doctor know if anything has changed.

Dementia: Women over age 65 receiving combined hormone replacement therapy may be at increased risk of developing dementia (loss of memory and intellectual function). If you are over 65, talk to your doctor about whether you should be tested for dementia.

Diabetes: Estrogen may cause a loss of blood glucose control, and glucose tolerance may change. People with diabetes may find it necessary to monitor their blood sugar more frequently while using this medication. If you have diabetes or are at risk for developing diabetes, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Endometrial cancer: There is evidence that estrogen replacement therapy can increase the risk of cancer of the endometrium (lining of the uterus). Women who have an intact uterus and are taking estradiol alone are at risk for developing a condition called endometrial hyperplasia, which can lead to the development of cancer of the uterus (endometrial cancer). The drospirenone (progestin) in this medication should counteract the risk of endometrial cancer.

Endometriosis: Estrogen replacement therapy can cause endometriosis to reappear or get worse. If you have or have had endometriosis, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Familial hypertriglyceridemia: If you have a condition known as familial hypertriglyceridemia (a disorder leading to high levels of fats known as triglycerides in the blood), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Follow-up examinations: It is important to have a follow-up examination 3 to 6 months after starting this medication to assess the response to treatment. Examinations should be done at least once a year after the first one. Make sure you keep all appointments made with your doctor.

Gallbladder disease: This medication can aggravate gallbladder disease or increase the risk of developing it. If you have gallbladder disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Heart disease and stroke: Studies indicate an increased risk of heart disease and stroke with estrogen (with or without progestin) for postmenopausal women. Get immediate medical attention if you experience symptoms of a heart attack (chest pain, tightness, or pressures; sweating; nausea; feeling of impending doom) or stroke (sudden dizziness, headache, loss of speech, changes in vision, weakness or numbness in the arms and legs).

Hypercalcemia and kidney disease: Prolonged use of estrogens can change the metabolism of calcium and phosphorus. If you have a disorder that changes the levels of calcium and phosphorus in the blood, such as metabolic or malignant bone diseases or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Kidney disease: Estrogens can cause fluid to build up in the body, which may affect kidney function. If you have kidney disease or decreased kidney function, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your kidney function regularly with blood tests while you are taking this medication

Liver disease: Estrogens can cause decreased liver function or liver failure. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication.

Liver tumours: In rare instances, cancerous and non-cancerous liver tumours have been noticed after using hormonal medications similar to drospirenone - estradiol. If you experience upper abdominal pain or enlargement, contact your doctor for assessment.

Seizure disorders: Estradiol may cause an increase in the frequency of seizures for people with seizure disorders. If you have a seizure disorder, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication

Thyroid disease: Estradiol can affect how thyroid hormone works in the body. Some people taking this medication develop changes in the function of their thyroid. Symptoms of these changes include feeling cold or hot all the time, a change in weight (gain or loss) without a change in your diet or amount of exercise you get, or feeling emotional. Contact your doctor if you experience these symptoms.

Uterine fibroids: Existing uterine fibroids may increase in size during estrogen use. This increase is usually minimal. However, if pain or tenderness occurs, inform your doctor as soon as possible. In some cases, the medication may need to be stopped.

Pregnancy: This medication must not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: Estrogens, such as estradiol, pass into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. This medication is not recommended for breast-feeding women.

Children: The safety and effectiveness of using this medication have not been established for children. This medication is not intended for use by children.

There may be an interaction between drospirenone - estradiol and any of the following:

• aliskiren
• anastrozole
• angiotensin-converting enzyme inhibitors (ACEIs; captopril, ramipril)
• angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
• apixaban
• "azole" antifungals (e.g., itraconazole, ketoconazole, voriconazole)
• barbiturates (e.g., pentobarbital, phenobarbital)
• bosentan
• clarithromycin
• clozapine
• cobicistat
• corticosteroids (e.g., cortisone, dexamethasone, prednisone)
• dehydroepiandrosterone
• diabetes medications (e.g., acarbose, canagliflozin, glyburide, insulin, linagliptin, lixisenatide, metformin, rosiglitazone)
• exemestane
• grapefruit juice
• heparin
• HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., efavirenz, etravirine,)
• HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir)
• lenalidomide
• low-molecular-weight heparins (e.g., dalteparin, enoxaparin, tinzaparin)
• melatonin
• mifepristone
• mitotane
• modafinil
• mycophenolate
• non-steroidal anti-inflammatory medications (NSAIDs; e.g., diclofenac, ibuprofen, naproxen)
• potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene)
• protein kinase inhibitors (e.g., crizotinib, dasatinib, lapatinib, nilotinib, sunitinib)
• quinine
• rifabutin
• rifampin
• rivaroxaban
• ropinirole
• St. John's wort
• seizure medications (e.g., carbamazepine, clobazam, lamotrigine, phenobarbital, phenytoin, primidone
• somatropin
• tacrolimus
• theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
• thyroid replacements (e.g., desiccated thyroid, levothyroxine)
• tizanidine
• tranexamic acid
• ursodiol
• warfarin

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.