Raloxifene adverse effects

Adverse effects of raloxifene include hot flashes, leg cramps, and increased risk of venous thromboembolism. Hot flashes are very common and may be intolerable in postmenopausal women who are already predisposed to experiencing them. A more serious adverse effect is a threefold increased risk of venous thromboembolism that was found in patients treated in the MORE trial.30 A previous history of venous thromboembolism is a contraindication to therapy. 

As a result of these findings, a scheduled standard pelvic exploration is now an obligatory procedure in clinical trials with new SERMs. It is important to note that this adverse effect has not been associated with tamoxifen or toremifene therapy (Maenpaa et al. 1997 Fisher et al. 1998), and in the case of raloxifene, a post hoc metaanalysis of 6926 nonhysterectomized postmenopausal women participating in clinical trials for 3 years or more showed a significant 50% reduction in the incidence of surgery for repairing pelvic floor relaxation, reported as an adverse event, compared with placebo (Goldstein et al. 2001). 

Finally, and with respect to raloxifene, Grady et al. (2004), when analyzing the safety and adverse effects associated with raloxifene in the MORE study, noticed that this did not increase the risk for gallbladder disease. 

Grady D, Ettinger B, Moscarelli E, Plouffe L Jr, Sarkar S, Ciaccia A, Cummings S, Multiple Outcomes of Raloxifene Evaluation Investigators (2004) Safety and adverse effects associated with raloxifene multiple outcome of raloxifene evaluation. Obstet Gynecol 104 837-844... 

The uses and adverse effects of raloxifene have been reviewed (8-12). Current work seems to show an altogether positive effect of raloxifene (for example 60 mg/ day) on bone metabolism and serum lipids in post-meno-pausal women on chronic hemodialysis, without significant adverse effects in the short term. However, even the authors of very promising work in this connection point to the difficulty in assessing the long-term safety of the treatment in such women (13). Longer-term work elsewhere has pointed particularly to the occurrence of thromboembolic disease, but also of hot flushes, influenza-like symptoms, peripheral edema, and leg cramps. With the exception of thromboembolism these are unpleasant rather than serious, but they still need to be recorded and studied in this very susceptible group of users. 

Since both raloxifene and the non-hormonal drug alendronate reduce the incidence of osteoporotic fractures in postmenopausal women it is relevant to determine which approach is better tolerated and thus most likely to promote long-term adherence to therapy. Adverse effects and compliance have been studied in a direct randomized comparison over 12 months in 902 women attending 154 treatment centres in Spain (21). They took either raloxifene 60 mg/day or alendronate 10 mg/day. Those who took raloxifene reported significantly better compliance than those who took alendronate more patients discontinued alendronate prematurely than raloxifene (26% versus 16%. The main reason for premature discontinuation was adverse reactions, particularly gastrointestinal reactions (9.9% with alendronate, 3.4% with raloxifene). 

Most clinical work with raloxifene 60 mg/day for the treatment of osteoporosis and lipid disorders in the menopause has been performed in Western populations. A multinational multicenter study in 483 Asian women (and a similar placebo control group) treated for 1 year has now confirmed that the efficacy and the adverse effects of the treatment are very similar to those in western populations (32). 

Raloxifene is approved for use in the treatment and prophylaxis of osteoporosis. As shown in the table opposite, it has other beneficial as well as adverse effects. 

Raloxifene exerts an estrogen-like effect on bone, while acting as an estrogen antagonist in the uterus and breast tissue (p. 254). In terms of fracture prophylaxis, its effectiveness appears inferior to that of bisphosphonates. Thromboembolism and edema are reported as adverse effects. 

The use and adverse effects of raloxifene have been reviewed (8-10). Many centers continue to examine this and other SERMs, for example in countering menopausal bone loss (11), in the hope that they can take the place of tamoxifen and provide a means of avoiding the risks of such complications as endometrial cancer, cataract, and stroke (12-14). 

Raloxifene generally is well tolerated. Its adverse effects include leg cramps and hot flushes. Raloxifene is used specifically to reduce the risk of osteoporosis in postmenopausal women. 

Raloxifene 60 mg/day Raloxifene reduces the risk of vertebral fractures. Adverse effects include hot flushes and leg cramps. Slowly increasing the dose of raloxifene may help reduce the incidence and severity of hot flushes. 

Raloxifene reduces the rate of bone loss and may increase bone mass at certain sites. In a large clinical trial, raloxifene increased spinal bone mineral density by more than 2% and reduced the rate of vertebral fractures by 30 to 50%, but did not significantly reduce nonvertebral fractures. Raloxifene does not appear to increase the risk of developing endometrial cancer. The drug has beneficial actions on lipoprotein metabolism, reducing both total cholesterol and LDL however, HDL is not increased. Adverse effects include hot flashes, deep vein thrombosis, and leg cramps. 

Selective Estrogen Receptor Modulators Raloxifene (EVISTa) acts as an estrogen agonist on bone and liver, is inactive on the uterus, and acts as an estrogen antagonist on the breast. In postmenopausal women, raloxifene modestly increases bone mineral density and has been shown to reduce the risk of vertebral compression fractures in this setting, it is approved for both the prevention and treatment of osteoporosis. The major adverse effect is worsened vasomotor symptoms the drug also increases the incidence of deep venous thrombosis. 

Raloxifene Raloxifene is used for prevention of osteoporosis in postmenopausal women. It has partial agonist effects on bone and increases serum HDL. Like tamoxifen, raloxifene has antagonist effects in breast tissue and reduces the incidence of breast cancer in women who are at very high risk. Unlike tamoxifen, the drug has no estrogenic effects on endometrial tissue. Adverse effects include hot flushes and increased risk of venous thrombosis. 

Raloxifene is the only selective oestrogen receptor modulator approved for long-term treatment in the prevention of osteoporotic fractures and for the reduction of invasive breast cancer risk in postmenopausal women. The efficacy and adverse effects of raloxifene as well as its molecular mechanism of action have been recently updated. It is noteworthy that quality-of-life studies demonstrated some favourable effects of raloxifene [32 ]. 

Gizzo S, Saccardi C, PatreUi TS, Berretta R, Capobianco G, Di Gangi S, et al. Update on raloxifene mechanism of action, clinical efficacy, adverse effects, and contraindications. Obstet Gynecol Surv 2013 68(6) 467-81. 

An extensive literature review has provided a useful assessment of the benefit to harm balance of raloxifene (20). The findings were reassuring. One large fracture prevention trial provided the best evidence that raloxifene 60 mg/day for 3 years reduced the relative risk of vertebral fractures by 30-50% in women with prevalent fractures or osteoporosis. The extraskeletal effects of raloxifene include a reduction in total cholesterol and low density lipoprotein cholesterol concentrations. Raloxifene was not associated with endometrial hyperplasia, and there was a 72% reduction in the incidence of invasive breast cancer. Adverse events associated with raloxifene included an increase in the absolute risk of venous thromboembolism and increased risks of hot... 

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