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    CE & BZA
    Efficacy & Safety
    DUAVEE® Logo
    DUAVEE® Logo

    Safety and Tolerability

    Please be advised that DUAVEE is currently out of stock. For medical questions on DUAVEE and for supply updates, please contact Pfizer Medical Information at 1‑800‑438‑1985.

    The safety and tolerability of DUAVEE® (conjugated estrogens/bazedoxifene) tablets were evaluated in 4 phase III trials ranging from 12 weeks to 24 months in duration1​​​​​​​

    Adverse events (AEs)

    Adverse reactions (incidence ≥5%) more common in the DUAVEE treatment group in placebo-controlled trials1

    Content

    DUAVEE 
    (n=1224) 
    n (%)

    PLACEBO
    (n=1069) 
    n (%)

    Gastrointestinal disorders

    Nausea

    100 (8)

    58 (5)

    Diarrhea

    96 (8)

    57 (5)

    Dyspepsia

    84 (7)

    59 (6)

    Abdominal pain upper

    81 (7)

    58 (5)

    Musculoskeletal and connective tissue disorders

    Muscle spasms

    110 (9)

    63 (6)

    Neck pain

    62 (5)

    46 (4)

    Nervous system disorders

    Dizziness

    65 (5)

    37 (3)

    Respiratory, thoracic, and mediastinal disorders

    Oropharyngeal pain

    80 (7)

    61 (6)

    Serious AEs

    Incidence of serious AEs was 3.5% in the DUAVEE group vs 4.8% in the placebo group1

    Discontinuations due to AEs

    Discontinuations due to AEs similar to placebo1

    The most common AEs leading to discontinuations were hot flash (DUAVEE 0.7%; placebo 1.8%), abdominal pain upper (DUAVEE 0.5%; placebo 0.5%), and nausea (DUAVEE 0.5%; placebo 0.7%)1,2​​​​​​​

    Cumulative amenorrhea

    8 of 10 patients reported no bleeding or spotting from the start of treatment through the course of 1 year, comparable to placebo1

    *The number of women included in the analysis of cumulative amenorrhea were as follows: Study 1: DUAVEE n=429; placebo n=421. Study 2: DUAVEE n=355; placebo n=379.2

    VTE

    Venous thromboembolism (VTE) and clinical trial data1

    The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT). Should any of these occur or be suspected, DUAVEE should be discontinued immediately.

    Estrogen agonist/antagonists, including bazedoxifene, and estrogens individually are known to increase the risk of VTE.

    In the clinical studies with DUAVEE, the reporting rates for VTE were low in all treatment groups. Adverse reactions of VTE were reported in 0.0% of patients treated with DUAVEE (n=1224) and 0.1% of patients treated with placebo (n=1069).

    Due to the low rate of events in both groups, it is not possible to conclude that the risk of VTE with DUAVEE is different from that seen with other estrogen therapies.

    Study descriptions

    Study 1

    A multicenter, double-blind, randomized, placebo- and active-controlled, 24-month study of the effects of bazedoxifene/conjugated estrogens combinations on endometrial hyperplasia and prevention of osteoporosis in postmenopausal women with a uterus. Women were aged 40-75 years (mean 56 years) and postmenopausal was defined as having last menstrual cycle at least 12 months before screening, serum FSH at least 30 mIU/mL and 17β-estradiol <50 pg/mL. The primary endpoint was the incidence of endometrial hyperplasia at year 1. Bone mineral density (BMD) change at the lumbar spine at year 2 was the key secondary endpoint assessed in two substudies. Substudy I included women more than 5 years postmenopausal with lumbar spine or total hip T-score of -1 to -2.5, and at least one additional risk factor for osteoporosis. Substudy II included women 1-5 years postmenopausal with at least one additional risk factor for osteoporosis. BMD change at the total hip at year 2 was also assessed as a secondary endpoint. In both substudies, women took calcium (600-1200 mg) and vitamin D (200-400 IU) daily. Another secondary endpoint was cumulative amenorrhea as recorded by daily diary. The study enrolled a total of 3397 women: DUAVEE, n=433; placebo, n=427; other bazedoxifene/conjugated estrogens doses, n=2114; and active comparator, n=423.

    Study 2

    A multicenter, double-blind, randomized, placebo- and active-controlled, 12-month study of the effects of bazedoxifene/conjugated estrogens combinations on endometrial hyperplasia and prevention of osteoporosis in postmenopausal women with a uterus. Women were aged 41-64 years (mean 54 years) and postmenopausal was defined as at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH level >40 mIU/mL. The primary endpoint was the incidence of endometrial hyperplasia at year 1. Bone mineral density (BMD) change at the lumbar spine at 12 months was the key secondary endpoint assessed in a substudy of women who were less than 5 years postmenopausal. BMD change at the total hip at 12 months was also assessed as a secondary endpoint. Women in the substudy took calcium (600-1200 mg) and vitamin D (200-400 IU) daily. Another secondary endpoint was cumulative amenorrhea as recorded by daily diary. The study enrolled a total of 1843 women: DUAVEE, n=445; placebo, n=474; other bazedoxifene/conjugated estrogens dose, n=474; bazedoxifene alone, n=230; and active comparator, n=220.


    References:
    1. DUAVEE [package insert]. New York, NY: Pfizer Inc.; 2019.
    2. Data on file, Pfizer Inc., New York, NY.

    Efficacy & Safety

    INDICATIONS

    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.

    Women taking DUAVEE® (conjugated estrogens/bazedoxifene) should not be taking progestins, additional estrogens, or additional estrogen agonist/antagonists.

    There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. DUAVEE contains bazedoxifene, an estrogen agonist/antagonist, to reduce the risk of endometrial hyperplasia that can occur with estrogens, and which may be a precursor to endometrial cancer. 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.

    Estrogen therapy should not be used for the prevention of cardiovascular disease or dementia.

    The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT). Should any of these occur or be suspected, DUAVEE should be discontinued immediately.

    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.

    DUAVEE should not be used in women with undiagnosed abnormal uterine bleeding; known, suspected, or past history of breast cancer or estrogen-dependent neoplasia; active or past history of venous or arterial thromboembolism; hypersensitivity to estrogens, bazedoxifene, or any ingredients; known hepatic impairment or disease; known thrombophilic disorders. Women who are pregnant should not use DUAVEE.

    Estrogen agonist/antagonists, including bazedoxifene, and estrogens individually are known to increase the risk of VTE.

    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 and ovarian cancer is unknown.

    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, because estrogens may be associated with increased thyroid binding globulin (TBG) levels.

    Adverse reactions more common in the DUAVEE treatment group in four placebo-controlled studies were muscle spasms, nausea, diarrhea, dyspepsia, abdominal pain upper, oropharyngeal pain, dizziness, and neck pain.

    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.

    Please see Full Prescribing Information, including BOXED WARNING and Patient Information.