General Information

Duavee pairs conjugated estrogens with bazedoxifene. Bazedoxifene (TSE-424) is a selective estrogen receptor modulator (SERM) designed to mimic the beneficial qualities of estrogens, while blocking estrogen in tissues where it can be harmful. The pairing of conjugated estrogens with bazedoxifene produces a composite effect that is specific to each target tissue.

Duavee is specifically indicated for the treatment of moderate to severe vasomotor symptoms associated with menopause and the prevention of postmenopausal osteoporosis.

Duavee is supplied as a tablet for oral administration. The recommended dose is one tablet once a day.

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. Conjugated estrogens are composed of multiple estrogens and are agonists of ER- a and ß. Bazedoxifene is an estrogen agonist/antagonist that acts as an agonist in some estrogen-sensitive tissues and an antagonist in others. The pairing of conjugated estrogens with bazedoxifene produces a composite effect that is specific to each target tissue. The bazedoxifene component reduces the risk of endometrial hyperplasia that can occur with the conjugated estrogens component.

Side Effects

Adverse events associated with the use of Duavee may include, but are not limited to, the following:

• muscle spasms
• nausea
• diarrhea
• dyspepsia
• abdominal pain
• oropharyngeal pain
• dizziness
• neck pain

The Duavee drug label comes with the following Black Box 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 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) 
• 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

Clinical Trial Results

The FDA approval of Duavee was based on the following clinical trials:

Moderate to Severe Vasomotor Symptoms Associated with Menopause
A double blind, randomized placebo controlled trial enrolled 318 women ages 42 to 64 with at least 7 moderate to severe hot flashes per day or 50 per week at baseline. Duavee significantly reduced the number and severity of moderate to severe hot flushes, as measured by the daily severity score, compared with placebo at Weeks 4 and 12.

Prevention of Postmenopausal Osteoporosis
Two studies were conducted: Study 1 and 2. Study 1 was a 24-month, double-blind, randomized, placebo- and active-controlled study evaluating the safety and efficacy of multiple combinations of conjugated estrogen/bazedoxifene (including conjugated estrogens 0.45 mg/bazedoxifene 20 mg) compared to placebo. A total of 3,397 women were enrolled. Duavee significantly increased lumbar spine bone mineral density (BMD) at 24 months compared to placebo. Duavee also significantly increased total hip BMD. The treatment difference (or difference from placebo) in total hip BMD at 24 months was 1.96% (Duavee minus placebo) in women who had been postmenopausal between 1 and 5 years and 1.73% (Duavee minus placebo) in women who had been postmenopausal for more than 5 years. Study 2 was a 12-month, double-blind, randomized, placebo- and active-controlled study. Duavee significantly increased mean lumbar spine BMD (treatment difference, 1.51%), at 12 months compared to placebo in women who had been postmenopausal between 1 and 5 years. Treatment with Duavee also increased total hip BMD. The treatment difference in total hip BMD at 12 months was 1.21%. The effect of Duavee on endometrial hyperplasia and endometrial malignancy were also assessed in Study 1 and Study 2. By endometrial biopsy, the incidence of endometrial hyperplasia or malignancy for Duavee was below 1% in both studies.