For these reasons, raloxifene increases the risk of thrombosis.Raloxifene increases bone mineral density in postmenopausal women but decreases it in premenopausal women. In the MORE trial, the risk of vertebral fractures was decreased by 30%, and bone mineral density was increased in the spine (by 2.1% at 60 mg, 2.4% at 120 mg) and femoral neck (2.6% at 60 mg, 2.7% at 120 mg). It has been found to possess estrogenic effects in adipose tissue in postmenopausal women, promoting a shift from an android fat distribution to a gynoid fat distribution. The medication has been found to increase levels of leptin, an adipokine. Pharmacokinetics
Absorption
The absorption of raloxifene is approximately 60%. However, due to extensive first-pass metabolism, the absolute bioavailability of raloxifene is only 2.0%. Raloxifene is rapidly absorbed from the intestines upon oral administration. Peak plasma levels of raloxifene occur 0.5 to 6 hours after an oral dose. In healthy postmenopausal women treated with 60 mg/day raloxifene, peak circulating raloxifene levels normalized by dose and body weight were (i.e., divided by (mg/kg)), 0.50 ng/mL (500 pg/mL) after a single dose and 1.36 ng/mL (1,360 pg/mL after multiple doses). Distribution
Raloxifene is widely distributed throughout the body. There is extensive distribution of raloxifene into the liver, serum, lungs, and kidneys. The volume of distribution of raloxifene with a single 30 to 150 mg oral dose is approximately 2348 L/kg, which corresponds to ~170,000 L for a 72 kg person.
Raloxifene may infrequently cause serious blood clots to form in the legs, lungs, or eyes. Other reactions experienced include leg swelling/pain, trouble breathing, chest pain, and vision changes. Black box warnings were added to the label of raloxifene in 2007 warning of increased risk of death due to stroke for postmenopausal women with documented coronary heart disease or at increased risk for major coronary events, as well as increased risk for deep vein thrombosis and pulmonary embolism. The risk of venous thromboembolism with raloxifene is increased by several-fold in postmenopausal women (RR = 3.1). Raloxifene has a lower risk of thromboembolism than tamoxifen. In the MORE trial, raloxifene caused a 40% decrease in risk of cardiovascular events in women who were at increased risk for coronary artery disease, although there was no decrease in cardiovascular events for the group as a whole.A report in September 2009 from Health and Human Services Agency for Healthcare Research and Quality suggests that tamoxifen and raloxifene used to treat breast cancer, significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects.A recent human case report in July 2016 suggests that raloxifene may in fact, at some point, also stimulate breast cancer growth leading to a reduction of advanced breast cancer disease upon the withdrawal of the drug.Unlike other SERMs, such as tamoxifen, raloxifene has no risk of uterine hyperplasia or endometrial cancer (RR = 0.8).Raloxifene does not increase the incidence of breast pain or tenderness in postmenopausal women.