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

    CE and BZA in DUAVEE

    Announcement Title

    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.

    DUAVEE® (conjugated estrogens/bazedoxifene) tablets provides a novel mechanism of action1

    CE activates estrogen receptors…2 

    • Vasomotor symptoms are related to estrogen decline in postmenopausal patients3
    • The CE in DUAVEE help address this decline by binding to and activating estrogen receptors, which vary in proportion from tissue to tissue2

    ​​​​​​​CE provide significant relief of moderate to severe hot flashes due to menopause and help prevent postmenopausal osteoporosis.2

    BZA reduces estrogen activity in select estrogen-sensitive tissues (eg, the uterine lining)2 

    • DUAVEE uses BZA instead of a progestin to help protect the uterine lining from endometrial hyperplasia associated with estrogen-alone treatment2
      • ​​​​​​​​​​​​<1% incidence of endometrial hyperplasia or malignancy in two studies of 12 and 24 months in duration*

        ​​​​​​​The systemic exposures of both CE and BZA were lower in obese subjects (BMI ≥30) compared to nonobese subjects. A greater reduction in BZA exposure compared to CE may be associated with decreased protection from endometrial hyperplasia
    • BZA was specifically selected for DUAVEE because of its unique pharmacologic profile, as demonstrated by preclinical studies that looked at a number of different SERMs4

    *Year 1: Study 1 DUAVEE 0/336; Study 2 DUAVEE 1/335. Year 2: Study 1 DUAVEE 2/294.

    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. ​​​​​​​Kharode Y, Bodine PVN, Miller CP, Lyttle CR, Komm BS. The pairing of a selective estrogen receptor modulator, bazedoxifene, with conjugated estrogens as a new paradigm for the treatment of menopausal symptoms and osteoporosis prevention. Endocrinology. 2008;149(12):6084-6091.
    2. DUAVEE [package insert]. New York, NY: Pfizer Inc.; 2019.
    3. Gass ML, Rebar R. The menopause. Glob Libr Womens Med. (ISSN: 1756-2228) 2008;doi 10.3843/GLOWM.10079.
    4. Crabtree JS, Peano BJ, Zhang X, Komm BS, Winneker RC, Harris HA. Activity of three selective estrogen receptor modulators on hormone-dependent responses in the mouse uterus and mammary gland. Mol Cell Endocrinol. 2008;287(1-2):40-46.

    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.