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 Duavive. If you are concerned about side effects, discuss the risks and benefits of Duavive with your doctor.

The following side effects have been reported by at least 1% of people taking Duavive. 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 pain
• abnormal dreams
• Acne
• appetite changes
• breast tenderness
• decreased sense of touch
• Diarrhea
• dizziness
• dry eyes
• ear discomfort, hearing changes
• feeling hot
• hair loss
• heartburn
• gas
• menstrual cramps or spotting
• Motion Sickness
• muscle pain or spasms
• nausea
• nosebleeds
• rash
• vomiting

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:

• breast lumps
• fluid retention (swelling of the lower legs, ankles, feet, or fingers)
• high blood pressure
• mood swings
• panic attacks
• pounding or rapid heartbeat
• symptoms of an infection (e.g., Fever, cold-like symptoms)
• 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)
• symptoms of a blood clot in the leg (e.g., pain or swelling in the leg)
• symptoms of a urinary tract infection (e.g., pain when urinating, urinating more often than usual, low back or flank pain)
• unexpected vaginal bleeding
• vaginal infection

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

• coughing blood
• headache (sudden or severe)
• sudden shortness of breath, coughing up blood, or sharp pain in chest
• sudden vision changes (such as partial or complete loss of vision, double vision)
• symptoms of a Anaphylaxis (severe allergic reaction) (e.g., Hives; difficult breathing; swelling of the face, mouth, throat, or tongue)
• symptoms of a heart attack (e.g., chest pain or pressure, pain extending through shoulder and arm, nausea and vomiting, sweating)
• symptoms of a stroke (e.g., sudden and severe headache, sudden vision changes, sudden difficulty speaking, sudden weakness or numbness in arms or legs, sudden dizziness, fainting, or vomiting)

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 Duavive.

Each oval, biconvex, pink modified-release tablet branded with "0.45/20" in black ink on one side contains 0.45 mg of conjugated estrogens in an extended release core and 20 mg of bazedoxifene (as bazedoxifene acetate) in an immediate release coating. Nonmedicinal ingredients: ascorbic acid, black iron oxide, calcium phosphate tribasic, hydroxyethylcellulose, hydroxypropyl cellulose, hypromellose, lactose monohydrate, magnesium stearate, maltitol, microcrystalline cellulose, poloxamer 188, polyethylene glycol, polydextrose, povidone, powdered cellulose, propylene glycol, red iron oxide, sucrose, sucrose palmitic acid ester, and titanium dioxide.

Do not take Duavive if you:

• are allergic to estrogen, bazedoxifene, or any ingredients of the medication
• are or may become pregnant
• are breast feeding
• have eye damage resulting from blood vessel disease of the eye, such as a partial or complete loss of vision
• have, have had, or may have Breast Cancer
• have liver disease
• have a history of Heart Attack, coronary heart disease or Stroke caused by a blood clot
• have or have had Thrombophlebitis or thromboembolic disorders (blood clotting problems) such as a blood clot in the lung or the large muscle of the leg
• have certain hereditary blood clotting disorders (e.g., protein C, protein S, or antithrombin deficiency)
• have or have had overgrowth of the endometrium
• have or may have a tumour dependent on estrogen
• have undiagnosed abnormal vaginal bleeding

There may be an interaction between bazedoxifene - conjugated estrogen and any of the following:

• Anastrozole
• Apixaban
• argatroban
• Bosentan
• cannabis
• Carbamazepine
• Celecoxib
• Clozapine
• Cyclosporine
• Cyproterone
• dabigatran
• Dabrafenib
• Deferasirox
• dehydroepiandrosterone
• diabetes medications (e.g., chlorpropamide, glipizide, Glyburide, insulin, Metformin, Rosiglitazone)
• Edoxaban
• efavirenz
• Eslicarbazepine
• etravirine
• Exemestane
• Heparin
• hyaluronidase
• Lenalidomide
• low-molecular-weight heparins (e.g., Dalteparin, Enoxaparin, Tinzaparin)
• Mitotane
• Modafinil
• oral corticosteroids (e.g., Dexamethasone, Hydrocortisone, Prednisone)
• Phenobarbital
• Phenytoin
• primidone
• rifabutin
• rifampin
• ritonavir
• Rivaroxaban
• Ropinirole
• St. John's wort
• siltuximab
• Somatropin
• Teriflunomide
• thalidomide
• theophyllines (e.g., Aminophylline, Oxtriphylline, Theophylline)
• thyroid replacements (e.g., dessicated thyroid, Levothyroxine)
• tipranavir
• Tizanidine
• Tocilizumab
• Ursodiol
• vitamin C
• 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 Duavive. 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.

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 Duavive.

Note the following important information about estrogen replacement therapy:

The Women's Health Initiative (WHI) study results indicated an increased risk of heart attack, stroke, breast cancer, Blood Clots in the lungs, and blood clots in the leg veins in postmenopausal women during 5 years of treatment with 0.625 mg conjugated equine estrogens and 2.5 mg medroxyprogesterone compared to women receiving sugar tablets. Other combinations of estrogen and progestins were not studied. However, until additional data are available, the risks should be assumed to be similar for other hormone replacement products. This means the following:

• Estrogens with or without progestins should be used at the lowest dose that relieves your menopausal symptoms for the shortest time period possible, as directed by your doctor.
• Estrogens with or without progestins should not be used to prevent heart disease, heart attacks, or strokes.

Blood clotting disorders: The use of estrogens is associated with an increased risk of blood clots in the lungs (pulmonary Embolism) and legs (deep vein thrombosis). If you have or have had a heart attack, stroke, heart disease, a blood clot in your leg, or medical conditions that increase your risk of blood clots, you should not use Duavive.

The risk of developing blood clots also increases with age, a personal or family history of blood clots, smoking, and Obesity. It is also increased if you are immobilized for prolonged periods or have major surgery. If possible, Duavive 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 estrogen replacement therapy. Talk to your doctor about how often you should have your blood pressure checked.

Bone disease: If you have bone disease due to cancer or a metabolic condition causing too much calcium in your body, discuss with your doctor how Duavive may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Duavive, and whether any special monitoring is needed.

Breast and Ovarian Cancer: Studies indicate an increased risk of breast and ovarian cancer with long-term use of estrogen replacement therapy. Women with a history of breast cancer should not use estrogens. Women who have breast nodules, fibrocystic disease, abnormal mammograms, or a strong family history of breast cancer should be closely monitored by their doctor.

Women taking estrogens should have regular breast examinations and should be instructed in breast self-examination. The Estradiol patch must not be applied to the breasts, as it may have harmful effects on the breast tissue.

Dementia: Women over the age of 65 receiving combined hormone replacement therapy (estrogen and progestin or estrogen alone) 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: Estrogens may affect blood sugar control. If you have diabetes or are at risk of developing diabetes (e.g., have a family history of diabetes, have high blood pressure or High Cholesterol, or are obese), carefully monitor your blood glucose levels while using Duavive.

Endometrial cancer: There is evidence from several studies that estrogen replacement therapy can increase the risk of cancer of the endometrium (lining of the uterus). Taking a SERM, such as bazedoxifene, along with the estrogen reduces this risk of endometrial cancer.

Break-through bleeding may occur early in treatment with Duavive. If you develop any abnormal vaginal bleeding later on while using Duavive, contact your doctor. If you have or have had endometrial cancer, you should not use Duavive.

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

Fibroids: Duavive may worsen fibroids by causing sudden enlargement, pain, or tenderness. If you notice these effects, contact your doctor.

Fluid retention: Estrogen may cause fluid retention, and worsen heart disease, Kidney Disease, or Asthma. Talk to your doctor if you have any concerns. If you experience worsening of these conditions while using Duavive, contact your doctor.

Follow-up examinations: It is important to have a follow-up examination 3 to 6 months after starting Duavive to assess your response to treatment. Examinations should be done at least once a year after the first one.

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

Heart disease and stroke: Studies indicate an increased risk of heart disease and stroke with estrogen for postmenopausal women. If you experience symptoms of a heart attack (chest pain, tightness or pressure, 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) while taking Duavive, get immediate medical attention.

High cholesterol or triglycerides: Estrogen and bazedoxifene may increase triglyceride levels in those who already have high levels. If you have increased cholesterol or triglycerides, discuss with your doctor how Duavive may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Duavive, and whether any special monitoring is needed.

Kidney function: Estrogen can affect how calcium and phosphorus are used by your body. If you have kidney disease, this may be a concern and you should discuss with your doctor how Duavive may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Duavive, and whether any special monitoring is needed.

Liver function: If you have reduced liver function, you may require special monitoring by your doctor while you use Duavive. Make sure to tell your doctor if you have ever had liver problems. People with active liver disease or liver tumours should not use estrogen.

If you experience symptoms of liver problems (e.g., yellowing of the skin or eyes, abdominal pain, loss of appetite, dark urine, pale stools, nausea, or vomiting), contact your doctor immediately.

Migraine Headaches: If you have migraines with aura (headache is associated with symptoms such as flashes of light, tingling sensations, blind spots, muscle weakness, and difficulty speaking either before or during the headache), you should not use Duavive.

For some people who experience migraine headaches, estrogen can aggravate the condition. Talk to your doctor if you notice any change in your migraine pattern while using estrogen.

Seizures: Estrogens may increase your risk of having a seizure. If you have a seizure disorder or a history of seizures, discuss with your doctor how Duavive may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Duavive, and whether any special monitoring is needed.

Thyroid disease: Estrogen may affect how thyroid hormone is used by the body. If you are taking thyroid medication to supplement an underactive thyroid gland, discuss with your doctor how Duavive may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Duavive, and whether any special monitoring is needed.

Pregnancy: Estrogen should not be used during pregnancy. If you become pregnant while taking Duavive, contact your doctor immediately.

Breast-feeding: Duavive passes into breast milk. If you are a breast-feeding mother and are taking estrogen, it may affect your baby. Duavive is not recommended for breast-feeding women.

Children: Duavive is not intended for children or adolescents.

Seniors: The safety and effectiveness of Duavive have not been determined for adult women older than 75 years of age.