Aprela, a single tablet formulation of bazedoxifene and conjugated equine estrogens (Premarin) for the potential treatment of menopausal symptoms

Aprela, in development by Pfizer Inc, is a once-daily, orally administered, tissue-selective estrogen complex that contains the selective estrogen receptor modulator bazedoxifene (BZA) and conjugated equine estrogens (CE). Aprela was designed as an alternative to combination estrogen and progestin therapy to treat the vasomotor symptoms associated with menopause without the potential safety concerns associated with combination estrogen/progestin therapy, and with better tolerability. Both estrogens and BZA bind to estrogen receptors (ER) alpha and beta, but when BZA binds to an ER, the result may be an estrogen agonistic or antagonistic effect. In contrast, progestins antagonize the effects of estrogen in the uterus, but along with estrogen, stimulate breast tissue increasing the risk for breast cancer. In phase III clinical trials, Aprela significantly reduced the number and severity of vasomotor symptoms, reduced vaginal atrophy and increased bone mineral density. However, higher doses of BZA tended to attenuate these positive effects of CE. At the time of publication, there were no clinical data from women taking Aprela for >2 years, and no definitive trials to determine the effects of Aprela on the risks for cardiovascular events, stroke, breast cancer, venous thromboembolism or cognitive function had been completed. Nevertheless, at the time of publication, Aprela was under consideration by the FDA for approval to treat vasomotor symptoms in postmenopausal women.