DUAVEE

AbsorptionFollowing 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 are summarized in Table 2.

Table 2Mean ± SD Steady-State Pharmacokinetic Parameters (n=24) C max (ng/mL) T max (hr) AUCss (ng∙hr/mL) Baseline-Adjusted Total E...

14.1 Treatment of Moderate to Severe Vasomotor Symptoms Associated with Menopause in Women with a Uterus The safety and efficacy of DUAVEE as a treatment for moderate to severe vasomotor symptoms associated with menopause was established in a 12-week randomized, double-blind, placebo-controlled study (Study 3). Study 3 enrolled a total of 318 women, age 42–64 (mean age of 53 years), who had at least 7 moderate to severe hot flushes per day or at least 50 per week at baseline. The mean number of years since menopause was 4.5 years with all women undergoing natural menopause. A total of 127 wome...

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) ] In four prospective, randomized, placebo-controlled trials the common adverse reactions (incidence ≥ 5%) were muscle spasms, nausea, diarrhea, dyspepsia, abdo...

DUAVEE is contraindicated in women with any of the following conditions:

• Undiagnosed abnormal uterine bleeding
• Known, suspected, or past history of breast cancer
• Known or suspected estrogen-dependent neoplasia
• Active deep venous thrombosis, pulmonary embolism, or history of these conditions
• Active arterial thromboembolic disease (for example, stroke, myocardial infarction) or history of ...

• Women taking DUAVEE should not take progestins, additional estrogens or additional estrogen agonist/antagonists ( 5.1 )
• Cardiovascular disorders, including venous thromboembolism, pulmonary embolism, stroke, and retinal vascular thrombosis ( 5.2 , 5.6 )
• Malignant neoplasms, including endometrial cancer, breast cancer, and ovarian cancer ( 5.3 )
• Estrogens increase the risk of gallbladder disease ( 5.5 )
• Discontinue estrogen if loss of vision, severe hypertriglyceridemia or cholestatic j...

7 DRUG INTERACTIONS 7.1 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 ...