Pharmacology Update
Conjugated Estrogens and Bazedoxifene Tablets (Duavee®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern
California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The first combination of conjugated estrogen and an estrogen agonist/antagonist (bazedoxifene) has been approved for the treatment of hot flashes. Bazedoxifene is a selective estrogen receptor modifier (SERM) that inhibits the estrogen effect on the endometrium. It is used in place of a progestin to reduce endometrial hyperplasia. Conjugated estrogens and bazedoxifene is marketed by Pfizer as Duavee.
Indications
The combination of conjugated estrogens and bazedoxifene (CE/BZA) is indicated for the treatment of moderate-to-severe vasomotor symptoms associated with menopause and for the prevention of postmenopausal osteoporosis in nonhysterectomized women.1
Dosage
The recommended dose is one tablet once daily. CE/BZA is available as a tablet containing conjugated estrogen 0.45 mg and bazedoxifene 20 mg.
Potential Advantages
In contrast to CE and medoxyprogesterone, CE/BZA does not increase mammographic breast density and showed lower rates of breast tenderness.2
Potential Disadvantages
In an animal model, BZA antagonized the atheroprotective effect of CE.3 CE/BZA is not recommended in patients with renal impairment and is contraindicated in those with hepatic impairment.1 BZA may be less effective in patients with a body mass index greater than 27 kg/m2.
Comments
The data for safety and efficacy of CE/BZA for the approved indications were from two Phase 3 Selective estrogens, Menopause and Response to Therapy (SMART) trials.4 For moderate-to-severe vasomotor symptoms, menopause subjects (n = 318) were between 42-64 years of age and had at least seven moderate-to-severe hot flashes per day or at least 50 per week. They were randomized to CE/BZA (n = 127) or placebo (n = 63). The primary endpoint was the reduction in the number and severity of hot flashes compared to placebo at 4 and 12 weeks. From an average baseline frequency of 10.3 daily, CE/BZA showed a statistically significant treatment difference of -3.1 (95% confidence interval [CI], -4.4, 1.7) compared to placebo at week 4 and -2.7 (95% CI, -3.8, -1.6) at week 12. Severity was significantly reduced from a baseline of 2.3 by -0.5 (95% CI, -0.7, -0.3) and -0.6 (95% CI, -0.9, -0.4), respectively. Prevention of osteoporosis was shown in a 24-month study.1,4 CE/BZA showed a difference (from placebo) in bone mineral density of 3.62% (95% CI, 2.64, 4.60) in those between 1 and 5 years postmenopausal. The difference for those who were postmenopausal longer than 5 years was 3.11% (95% CI, 2.29%, 3.93%). The incidence of endometrial hyperplasia assessed by biopsy was less than 1% at 24 months.1,4 CE/BZA is generally well tolerated. The frequency of adverse events was 7-9%, and included nausea, diarrhea, muscle spasm, upper abdominal pain, and oropharyngeal pain.1
Clinical Implications
CE/BZA provided an effective and perhaps safer alternative than estrogen/progestin combinations for treating vasomotor symptoms and preventing osteoporosis. The drug combines a traditional estrogen with a SERM. The long-term effects, especially on the risk of breast cancer, are intriguing as the drug is being widely touted in the lay press as being potentially protective. There are currently no data to support this claim. The cost of CE/BZA was not available at the time of this review.
References
- Duavee Prescribing Information. New York, NY: Pfizer Inc.; October 2013.
- Pinkerton JV, et al. Obstet Gynecol 2013;121:959-968.
- Clarkson TB, et al. Menopause 2013;20:274-281.
- Pinkerton JV, et al. J Womens Health 2014;23:18-28.
