These highlights do not include all the information needed to use                                       DUAVEE safely and effectively. See full prescribing information for DUAVEE. DUAVEE® (conjugated estrogens/bazedoxifene) tablets for oral use

 Initial U.S. approval: 2013

WARNING:

 ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, AND PROBABLE DEMENTIA See full prescribing information for complete Boxed Warning.

 • Women taking DUAVEE should not take additional estrogens                                             • There is an increased risk of endometrial cancer in a woman with a uterus who uses       unopposed estrogens                                                                                                          • Estrogen   • The Women’s Health Initiative (WHI) estrogen-alone substudy reported      increased risks of stroke and deep vein thrombosis (DVT)                                                   • The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported          an increased risk of probable dementia in postmenopausal women 65 years of age           and older

RECENT MAJOR CHANGES

­ Warnings and Precautions, Malignant Neoplasms  11/2017

INDICATIONS AND USAGE 

­ DUAVEE is a combination of conjugated estrogens with an estrogen agonist/antagonist indicated for treatment of the following conditions in women with a uterus:                        • Treatment of moderate to severe vasomotor symptoms associated with menopause       • Prevention of postmenopausal osteoporosis    

 Limitation of Use: DUAVEE should be used for the shortest duration consistent with treatment goals and risks for the individual woman

DOSAGE AND ADMINISTRATION                                                                                        • Take one tablet orally once daily

DOSAGE FORMS AND STRENGTHS-                                                                                ­ Tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg

ADVERSE REACTIONS

In four prospective, randomized, placebo-controlled trials the common adverse reactions (incidence = 5%) were muscle spasms, nausea, diarrhea, dyspepsia, abdominal pain upper, oropharyngeal pain, dizziness, and neck pain

CONTRAINDICATIONS

­ • Undiagnosed abnormal uterine bleeding                                                                             • Known, suspected, or past history of breast cancer                                                            • Known or suspected estrogen-dependent neoplasia                                                          • Active or past history of venous thromboembolism                                                            • Active or past history of arterial thromboembolism                                                            • Hypersensitivity (angioedema, anaphylaxis) to estrogens, bazedoxifene, or any                 ingredients                                                                                                                         • Known hepatic impairment or disease                                                                                 • Known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders        • Pregnancy, women who may become pregnant, and nursing mothers

 WARNINGS AND PRECAUTIONS-

­ • Women taking DUAVEE should not take progestins, additional estrogens or additional estrogen agonist/antagonists                                                                                                 • Cardiovascular disorders, including venous thromboembolism, pulmonary embolism,       stroke, and retinal vascular thrombosis                                                                               • Malignant neoplasms, including endometrial cancer, breast cancer, and ovarian             cancer                                                                                                                               • Estrogens increase the risk of gallbladder disease                                                            • Discontinue estrogen if loss of vision, severe hypertriglyceridemia or cholestatic             jaundice occurs                                                                                                                    • Monitor thyroid function in women on thyroid replacement therapy

 PATIENT COUNSELING INFORMATION-                                                                            See FDA-approved patient labelling (Patient Information).

1. Instructions for Patients-                                                                                                •Keep DUAVEE in the original container to protect from moisture. Do not place DUAVEE in pill boxes or pill organizers.                                                                                                • If more than one blister package is dispensed to the patient, instruct them to open one foil pouch at a time.                                                                                                               •Instruct patient to record the date the blister package is opened in the space provided on the blister package label. Do not use if the blister package has been open more than 60 days.                                                                                                                               • Instruct patient to remove only one tablet from the blister package at the time of use.

2. Venous Thromboembolic Events-                                                                                  Advise patients to immediately report to their physician any signs or symptoms related to venous thrombosis and thromboembolic events

3. Abnormal Vaginal Bleeding-                                                                                           Inform postmenopausal women of the importance of reporting abnormal vaginal bleeding to their healthcare provider as soon as possible

4. Possible Serious Adverse Reactions with Estrogen Therapy-                                   Inform postmenopausal women of possible serious adverse reactions of estrogen therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia

5. Possible Less Serious Adverse Reactions with DUAVEE-                                         Inform postmenopausal women of possible less serious but common adverse reactions of DUAVEE therapy such as muscle spasms, nausea, diarrhea, dyspepsia, upper abdominal pain, throat pain, dizziness and neck pain.

6. Calcium and Vitamin D Intake-                                                                                       Advise patients to add supplemental calcium and/or vitamin D to the diet if daily intake is inadequate.

Distributed by

Wyeth Laboratories Inc

 CLINICAL PHARMACOLOGY

1.Mechanism of Action-                                                                                                       DUAVEE pairs conjugated estrogens with bazedoxifene. Conjugated estrogens and bazedoxifene function by binding to and activating estrogen receptors (ER) a and ß, which vary in proportion from tissue to tissue.

2.Pharmacodynamics-                                                                                                studies have not been conducted with DUAVEE.

3. Pharmacokinetics-                                                                                                             Absorption-                                                                                                                        Following administration of multiple doses of conjugated estrogens 0.45 mg/bazedoxifene 20 mg to healthy women who were naturally postmenopausal or who had undergone bilateral oophorectomy, the mean steady state pharmacokinetic parameters at Day 10 for conjugated estrogens (baseline adjusted for total estrone) and bazedoxifene were studied

Results from monotherapy studies with conjugated estrogens or bazedoxifene components of DUAVEE, are noted below: Conjugated estrogens are soluble in water and are well-absorbed from the gastrointestinal tract after release from the drug formulation.        

Distribution-                                                                                                                         The distribution of conjugated estrogens and bazedoxifene after administration of DUAVEE has not been studied.                                                                                           

 Metabolism -                                                                                                                      The metabolic disposition of conjugated estrogens and bazedoxifene, after administration of DUAVEE, has not been studied.

Excretion-                                                                                                                             After administration of a single dose of conjugated estrogens/bazedoxifene, baseline-adjusted total estrone (representing conjugated estrogens) is eliminated with a half-life of approximately 17 hours. Bazedoxifene is eliminated with a half-life of approximately 30 hours.

Steady-state concentrations are achieved by the second week of once-daily administration.

Use in Specific Populations

Pediatric -                                                                                                                           The pharmacokinetics of conjugated estrogens/bazedoxifene tablets have not been evaluated in a pediatric population

Geriatric-                                                                                                                              The effect of age on the pharmacokinetics of conjugated estrogens/bazedoxifene tablets have not been evaluated

Renal Impairment-                                                                                                               The pharmacokinetics of conjugated estrogens/bazedoxifene tablets have not been evaluated in women with renal impairment

 Hepatic Impairment-                                                                                                          The pharmacokinetics of conjugated estrogens/bazedoxifene tablets have not been evaluated in women with hepatic impairment

No pharmacokinetic studies with conjugated estrogens were conducted in specific populations, including women with hepatic impairment

 USE IN SPECIFIC POPULATIONS

1. Pregnancy- Pregnancy Category X-                                                                                  DUAVEE must not be used in women who are or may become pregnant.     

    No studies were performed on animals to evaluate the effects on reproduction with           conjugated estrogens/bazedoxifene. 

  2.Nursing Mothers-                                                                                                               DUAVEE should not be used by lactating mothers                                                               It is not known whether this drug is excreted in human milk. Detectable amounts of          estrogens have been identified in the milk of mothers receiving conjugated estrogens.     Estrogen administration to nursing mothers has been shown to decrease the quantity        and quality of the milk.

3.Pediatric Use-                                                                                                                      DUAVEE is not indicated for use in children     

 4.Geriatric Use-                                                                                                                    DUAVEE is not recommended for use in women greater than 75 years of age            Of the total number of women in phase 3 clinical studies who received DUAVEE, 4.60% (n=224) were 65 years and over. DUAVEE was not studied in women aged 75 and over.

No overall differences in safety or effectiveness were observed between women 65-74 years of age and younger women, and other reported clinical experience has not identified differences in responses between the elderly and younger women, but greater sensitivity of some older women cannot be ruled out.

5.Renal Impairment-                                                                                                             DUAVEE is not recommended for use in patients with renal impairment .                           The pharmacokinetics, safety, and efficacy of DUAVEE have not been evaluated in women with renal impairment.

6. Hepatic Impairment-                                                                                                          DUAVEE is contraindicated in patients with hepatic impairment .                                      The pharmacokinetics, safety, and efficacy of DUAVEE have not been evaluated in           women with hepatic impairment.

 OVERDOSAGE

 In case of overdosage, there is no specific antidote, and the treatment should be symptomatic.       

Symptoms of overdosage of estrogen-containing products in adults and children may include nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue; withdrawal bleeding may occur.