Duavee

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using bazedoxifene and conjugated estrogens and call your doctor at once if you have:

• sudden vision loss;
• a lump in your breast;
• signs that you may need a lower dose--abnormal vaginal bleeding, dizziness, tiredness, stomach pain, vomiting, breast tenderness
• signs of a stroke--sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;
• signs of a blood clot in the lung--chest pain, sudden cough, wheezing, rapid breathing, coughing up blood;
• signs of a blood clot in your leg--pain, swelling, warmth, or redness in one or both legs;
• heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating; or
• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• mild dizziness;
• nausea, stomach pain or discomfort, diarrhea;
• neck pain, muscle spasm; or
• throat or sinus pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This medicine is usually taken once daily. Follow all directions on your prescription label. Bazedoxifene and conjugated estrogens is for short-term use at the lowest dose needed to treat your condition. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take bazedoxifene and conjugated estrogens with or without food. Take the medicine at the same time each day.

Do not crush, chew, or break the tablet. Swallow it whole.

Your doctor should check your progress on a regular basis to determine whether you should continue this treatment.

Have regular physical exams and mammograms, and self-examine your breasts for lumps on a monthly basis while using this medicine.

If you need surgery or medical tests or if you will be on bed rest, you may need to stop using this medication for a short time. Any doctor or surgeon who treats you should know that you are taking bazedoxifene and conjugated estrogens.

Your doctor may have you take extra calcium and vitamin D while you are taking bazedoxifene and conjugated estrogens. Take only the amount that your doctor has prescribed.

Store at room temperature away from moisture and heat. Keep each tablet in its blister pack until you are ready to take it. Do not use a pill box for this medicine.

Write down the date you open a Duavee foil pouch. After opening the pouch, you should use the medicine within 60 days.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Serious side effects have been reported with Duavee. See the “Duavee Precautions” section.

Common side effects of Duavee include the following:

• Nausea
• Heartburn
• Stomach pain
• Diarrhea
• Muscle tightness or spasms
• Neck pain
• Sore throat

This is not a complete list of Duavee side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated

The recommended dose of Duavee for the treatment of menopausal symptoms and prevention of postmenopausal osteoporosis is 0.45 mg/20 mg once daily. Take the medication at the same time every day.

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and does not cause unwanted effects. Pelvic exam, breast exam, and mammogram (breast x-ray) may be needed to check for unwanted effects, unless your doctor tells you otherwise. Be sure to keep all appointments.

It is unlikely that a postmenopausal woman may become pregnant. But, you should know that using this medicine while you are pregnant could harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.

Using this medicine may increase your risk for having blood clots, strokes, or heart attacks. This risk may continue even after you stop using the medicine. Your risk for these serious problems is even greater if you have high blood pressure, high cholesterol in your blood, diabetes or are overweight or smoke cigarettes. Contact your doctor immediately if you experience chest pain, confusion, difficulty speaking, double vision, headaches, an inability to move arms, legs or facial muscle, or an inability to speak.

Using this medicine may increase your risk of endometrial cancer, breast cancer, or uterine cancer. Talk with your doctor about this risk. Check with your doctor immediately if your experience abnormal vaginal bleeding.

Using this medicine may increase your risk of dementia, especially in women 65 years of age and older.

Check with your doctor immediately if severe headache or sudden loss of vision or any other change in vision occurs while you are using this medicine. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine before you have surgery or if you need to stay in bed for an extended time. This medicine may affect the results of certain medical tests.

Do not eat grapefruit or drink grapefruit juice while you are using this medicine. Grapefruit and grapefruit juice may change the amount of this medicine that is absorbed in the body.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Chest pain or pressure.
• Shortness of breath.
• Coughing up blood.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Very bad headache.
• Very bad dizziness or passing out.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Very upset stomach or throwing up.
• Very bad belly pain.
• Vaginal bleeding that is not normal.
• Vaginal itching or discharge.
• Bulging eyes.
• Change in how contact lenses feel in the eyes.
• Change in eyesight.
• Low mood (depression).
• Mood changes.
• Memory problems or loss.
• Breast pain.
• A lump in the breast, breast soreness, or nipple discharge.

• Store in the original container at room temperature.
• Use right away after Duavee is removed from the foil. Do not store any part of the tablet for use at a later time.
• Throw away any part not used after 2 months.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Duavee (estrogens (conjugated/equine) and bazedoxifene) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Duavee. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Drugs Containing Progestins, Estrogens or Estrogen Agonist/Antagonists

Duavee contains conjugated estrogens and bazedoxifene, an estrogen agonist/antagonist. Women taking Duavee should not take progestins, additional estrogens or additional estrogen agonist/antagonists.

Cardiovascular Disorders

Estrogen agonist/antagonists (including bazedoxifene, a component of Duavee) and estrogens individually are known to increase the risk of VTE.

An increased risk of stroke and DVT has been reported with estrogen-alone therapy. Should any of these occur or be suspected, Duavee should be discontinued immediately.

Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or VTE (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.

Stroke

In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily conjugated estrogens (CE) (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years). The increase in risk was demonstrated in year 1 and persisted [see Clinical Studies (14.5)].

Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving conjugated estrogens (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years).

Should a stroke occur or be suspected, Duavee should be discontinued immediately [see Contraindications (4)].

Coronary Heart Disease

In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (defined as nonfatal myocardial infarction, silent myocardial infarction, or CHD death) was reported in women receiving estrogen-alone compared to placebo [see Clinical Studies (14.5)].

Subgroup analyses of women 50 to 59 years of age suggest a statistically non-significant reduction in CHD events (CE [0.625 mg]-alone compared to placebo) in women with less than 10 years since menopause (8 versus 16 per 10,000 women-years).

Venous Thromboembolism (VTE)

In the WHI estrogen-alone substudy, the risk of VTE [DVT and pulmonary embolism (PE)] was increased for women receiving daily conjugated estrogens (0.625 mg)-alone compared to placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women-years). The increase in VTE risk was demonstrated during the first 2 years [see Clinical Studies (14.5)].

If feasible, Duavee should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. Because immobilization increases the risk for venous thromboembolic events independent of therapy, Duavee should be discontinued prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest) and Duavee therapy should be resumed only after the patient is fully ambulatory. In addition, women taking Duavee should be advised to move about periodically during travel involving prolonged immobilization.

Malignant Neoplasms

Endometrial Cancer

An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in women with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than 1 year. The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more of treatment. This risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued.

Duavee contains an estrogen agonist/antagonist. This component reduces the risk of endometrial hyperplasia that can occur with the conjugated estrogens component. Endometrial hyperplasia may be a precursor to endometrial cancer. Women taking Duavee should not take additional estrogens as this may increase the risk of endometrial hyperplasia.

Clinical surveillance of all women taking Duavee is important. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Breast Cancer

The most important randomized clinical study providing information about breast cancer in estrogen-alone users is the WHI substudy of daily conjugated estrogens (0.625 mg)-alone. In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily conjugated estrogen (0.625 mg)-alone was not associated with an increased risk of invasive breast cancer (relative risk [RR] 0.80).

The use of estrogen-alone has been reported to result in an increase in abnormal mammograms requiring further evaluation. The effect of treatment with Duavee on the risk of breast cancer is unknown.

All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results.

Ovarian Cancer

In some epidemiological studies, the use of estrogen-only products, in particular for 5 or more years, has been associated with an increased risk of ovarian cancer. However, the duration of exposure associated with increased risk is not consistent across all epidemiologic studies, and some report no association. The effect of treatment with Duavee on the risk of ovarian cancer is unknown.

Probable Dementia

In the WHIMS estrogen-alone ancillary study of WHI, a population of 2,947 hysterectomized women 65 to 79 years of age was randomized to daily CE (0.625 mg)-alone or placebo.

After an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent CI, 0.83–2.66). The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10,000 women-years [see Use in Specific Populations (8.5) and Clinical Studies (14.6)].

Gallbladder Disease

A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.

Visual Abnormalities

Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, Duavee should be permanently discontinued.

Elevated Blood Pressure

In a small number of case reports in women receiving estrogens, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo-controlled clinical study, a generalized effect of estrogens on blood pressure was not seen.

Hypertriglyceridemia

In women with pre-existing hypertriglyceridemia, treatment with estrogens may be associated with elevations of plasma triglycerides leading to pancreatitis. Consider discontinuation of Duavee if pancreatitis occurs.

Hepatic Impairment and Past History of Cholestatic Jaundice

Duavee has not been studied in women with impaired liver function or past history of cholestatic jaundice.

Estrogens may be poorly metabolized in women with impaired liver function.

On average, women with hepatic impairment treated with bazedoxifene alone showed a 4.3-fold increase in overall exposures compared with controls [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised; and in the case of recurrence, Duavee should be discontinued. Use of Duavee in patients with hepatic impairment is contraindicated [see Contraindications (4)].

Hypothyroidism

Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.

Fluid Retention

Estrogens may cause some degree of fluid retention. Because of this, patients who have conditions that might be influenced by this factor, such as cardiac dysfunction or renal impairment, warrant careful observation when estrogens are prescribed. Use of Duavee in patients with renal impairment is not recommended [see Use in Specific Populations (8.6)].

Hypocalcemia

Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur.

Hereditary Angioedema

Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema.

Exacerbation of Other Conditions

Estrogens may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine or porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.

Premenopausal Women

There is no indication for premenopausal use of Duavee. The efficacy and safety of Duavee in premenopausal women have not been established, and its use is not recommended.

Laboratory Tests

Serum follicle stimulating hormone (FSH) and estradiol levels have not been shown to be useful in the management of moderate to severe vasomotor symptoms.

Drug-Laboratory Test Interactions

Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.

Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay), or T3 levels by radioimmunoassay. T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Women on thyroid replacement therapy may require higher doses of thyroid hormone.

Other binding proteins may be elevated in serum, for example, corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations, such as testosterone and estradiol, may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).

Increased plasma high-density lipoprotein (HDL) and HDL2 cholesterol subfraction concentrations, reduced low-density lipoprotein (LDL) cholesterol concentrations, increased triglyceride levels.

Impaired glucose tolerance.

The following adverse reactions are discussed in greater detail in other sections of the label:

• Cardiovascular Disorders [see Warnings and Precautions (5.2)]
• Malignant Neoplasms [see Warnings and Precautions (5.3)]
• Gallbladder Disease [see Warnings and Precautions (5.5)]
• Hypertriglyceridemia [see Warnings and Precautions (5.8)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of conjugated estrogens/bazedoxifene was evaluated in four Phase 3 clinical trials ranging from 12 weeks to 24 months in duration and enrolling 6,210 postmenopausal women age 40 to 75 years (mean age 55 years). A total of 1,224 patients were treated with Duavee and 1,069 patients received placebo. Women enrolled in Studies 1 and 2 received calcium (600–1200 mg) and vitamin D (200–400 IU) daily, while women in Studies 3 and 4 received no calcium and vitamin D supplementation as part of the protocol.

The incidence of all-cause mortality was 0.0% in the Duavee group and 0.2% in the placebo group. The incidence of serious adverse reactions was 3.5% in the Duavee group and 4.8% in the placebo group. The percentage of patients who withdrew from treatment due to adverse reactions was 7.5% in the Duavee group and 10.0% in the placebo group. The most common adverse reactions leading to discontinuation were hot flush, abdominal pain upper, and nausea.

The most commonly observed adverse reactions (incidence ≥ 5%) more frequently reported in women treated with Duavee than placebo are presented in Table 1.

Venous thromboembolism: In the clinical studies with Duavee, the reporting rates for venous thromboembolism (deep venous thrombosis, pulmonary embolism, and retinal vein thrombosis) were low in all treatment groups. Adverse reactions of venous thromboembolism were reported in 0.0% of patients treated with Duavee and 0.1% of patients treated with placebo. Due to the low rate of events in both groups, it is not possible to conclude that the risk of venous thromboembolism with Duavee is different from that seen with other estrogen therapies [see Warnings and Precautions (5.2)].

Cytochrome P450 (CYP)

In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Concomitant administration of itraconazole, a strong CYP3A4 inhibitor, with Duavee, resulted in increases in bazedoxifene exposure (40%) and, to a lesser extent, conjugated estrogens exposure (9% for baseline-adjusted total estrone, 5% for total equilin), compared to Duavee alone [see Pharmacokinetics (12.3)]. Inducers of CYP3A4, such as St. John's Wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin, may reduce plasma concentrations of some estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile.

Bazedoxifene does not induce or inhibit the activities of major CYP isoenzymes. In vitro data suggest that bazedoxifene is unlikely to interact with co-administered drugs via CYP-mediated metabolism.

Uridine Diphosphate Glucuronosyltransferase (UGT)

Bazedoxifene undergoes metabolism by UGT enzymes in the intestinal tract and liver. The metabolism of bazedoxifene may be increased by concomitant use of substances known to induce UGTs, such as rifampin, phenobarbital, carbamazepine, and phenytoin. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Atorvastatin

Concomitant administration of bazedoxifene (40 mg daily) and atorvastatin (20 mg, single-dose) to healthy postmenopausal women did not affect the pharmacokinetics of bazedoxifene, atorvastatin or its active metabolites.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies with conjugated estrogens/bazedoxifene have not been conducted.

Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.

In 6-month oral gavage carcinogenicity studies of bazedoxifene in transgenic Tg.RasH2 mice, there was a drug-related increased incidence of benign, ovarian granulosa-cell tumors in female mice given 150 or 500 mg/kg/day. In a two-year dietary carcinogenicity study of bazedoxifene in rats (administered at 0.003%, 0.01%, 0.03%, or 0.1%) a drug-related marked increased incidence of benign, ovarian granulosa-cell tumors was observed in female rats at concentrations of 0.03% and 0.1%. Systemic exposure (AUC) of bazedoxifene in these groups was 3 and 8 times that observed in postmenopausal women administered 20 mg/day. In male rats, drug-related renal tumors (adenomas and carcinomas), in the presence of renal toxicity, were observed at all doses tested, which corresponded to exposure ratios of 0.06 to 5 times the clinical AUC at a dose of 20 mg.

Mutagenesis

Mutagenicity studies with conjugated estrogens/bazedoxifene have not been conducted.

Bazedoxifene was not genotoxic or mutagenic in a battery of tests, including in vitro bacterial reverse mutation assay, in vitro mammalian cell forward mutation assay at the thymidine kinase (TK+/-) locus in L5178Y mouse lymphoma cells, in vitro chromosome aberration assay in Chinese hamster ovary (CHO) cells, and in vivo mouse micronucleus assay.

Impairment of Fertility

Impairment of fertility studies with conjugated estrogens/bazedoxifene have not been conducted.

Female rats were administered daily dosages of 0.3 to 30 mg/kg bazedoxifene (0.03 to 10 times human AUC at the 20 mg dose) prior to and during mating with untreated males. Estrous cycles and fertility were adversely affected in all bazedoxifene-treated female groups.

Animal Toxicology and/or Pharmacology

In a 12-month study in ovariectomized rats, co-administration of conjugated estrogens (2.5 mg/kg/day) and bazedoxifene (0.1, 0.3, or 1 mg/kg/day) prevented the loss of bone mass at the spine, femur, and tibia with concomitant maintenance of biomechanical strength parameters.

NDC 0008-1123-12

Pfizer

Duavee®
(conjugated estrogens/
bazedoxifene)
tablets

0.45 mg/20 mg*

After opening foil pouch, product must be used
within 60 days.

Dispense and store product in original package
to protect from moisture.

30 tablets
Rx only

Package includes 2 blister cards
containing 15 tablets each.

Applies to bazedoxifene / conjugated estrogens: oral tablet

Along with its needed effects, bazedoxifene / conjugated estrogens may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking bazedoxifene / conjugated estrogens:

• Acid or sour stomach
• anxiety
• backache
• belching
• bloating
• change in vaginal discharge
• chest pain
• chills
• clear or bloody discharge from the nipple
• confusion
• constipation
• cough
• darkened urine
• difficulty with speaking
• dimpling of the breast skin
• dizziness or lightheadedness
• double vision
• fainting
• fast heartbeat
• fever
• full or bloated feeling or pressure in the stomach
• headache
• heartburn
• inability to move the arms, legs, or facial muscles
• inability to speak
• indigestion
• inverted nipple
• loss of appetite
• lump in the breast or under the arm
• nausea
• pain or feeling of pressure in the pelvis
• pain, redness, or swelling in the arm or leg
• pains in the stomach, side, or abdomen, possibly radiating to the back
• persistent crusting or scaling of the nipple
• redness or swelling of the breast
• slow speech
• sore on the skin of the breast that does not heal
• stomach discomfort, upset, or pain
• sudden shortness of breath or troubled breathing
• swelling of the abdominal or stomach area
• vaginal bleeding
• vomiting
• yellow eyes or skin

Some side effects of bazedoxifene / conjugated estrogens may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• muscle spasm
• throat pain
• upper abdominal or stomach pain

• Neck pain