The Therapeutics Initiative's objectives are unbiased review and dissemination of therapeutic evidence. Our recommendations are intended to apply to most patients; exceptional patients require exceptional approaches. We are committed to evaluate the effectiveness of our educational activities using the Pharmacare/PharmaNet databases without identifying individual physicians, pharmacies or patients. The Therapeutics Initiative is funded by the BC Ministry of Health through a 5-year grant to the University of BC. The Therapeutics Initiative provides evidence based advice about drug therapy, and is not responsible for formulating or adjudicating provincial drug policies. Raloxifene (EvistaŽ) Approved indication: Prevention and treatment of osteoporotic fractures in women after menopause. Mechanism of action: Acts selectively on estrogen receptors in a manner similar to tamoxifen; they both act as agonists on bone and liver receptors and as antagonists on breast and uterus receptors. Pharmacokinetics: About 60% of the drug is absorbed but because of extensive first-pass metabolism it has a low absolute bioavailability (2%). Half-life averages 28 hours with a wide range in different individuals. Raloxifene conjugates are mostly excreted in the feces. Evidence of effectiveness: Changes in bone mineral density and serum lipids do not necessarily correlate with desired clinical events, therefore trials and data on surrogate outcomes are purposely not included in this letter. For example in one trial fluoride increased bone mineral density and increased the incidence of non-vertebral fractures5, and in another trial estrogen/progestin treatment decreased LDL cholesterol and was not associated with a decrease in coronary events6. A large double-blind RCT comparing raloxifene, 60 mg and 120 mg with placebo has assessed incidence of fractures.7 In this 3-year trial, 7705 women, >2 years after menopause, were stratified into 2 defined groups: primary prevention (low bone mineral density and no previous vertebral collapse), and secondary prevention (at least one previous vertebral collapse). Outcomes for the 2 doses of raloxifene were not different; therefore combined data for the 2 doses are presented, except where indicated. The primary end point was the incidence of vertebral collapse (>20% reduction in vertebral height) detected on x-ray, an event of which most patients were not aware. This end point was detected in 6.6% of patients taking raloxifene, 60 mg, vs. 10.1% of patients taking placebo. In the secondary prevention group the ARR for this end point was 6.5% and in the primary prevention group it was 2.2% . Of the total radiologic vertebral collapses 12.3% were reported as causing back pain. These painful vertebral collapses were significantly decreased by raloxifene (0.6% vs 1.4%, ARR = 0.8%, NNT = 125 for 3 years). Non-vertebral fractures were not significantly decreased by raloxifene (8.5%) as compared with placebo (9.3%). Major adverse effects: Thromboembolic events occurred significantly more often with raloxifene as compared with placebo (1.0% vs 0.3%, ARI = 0.7%, NNH = 143 for 3 years). Other adverse events that occurred significantly more often in the raloxifene group are listed and expressed as ARI over placebo: influenza syndrome, 2.1%, hot flashes, 3.7%, leg cramps, 3.2% and peripheral edema, 1.5%. Note: Early breast cancer diagnoses occurred significantly less often in the raloxifene group, 0.3%, than in the placebo group, 1.1%, ARR = 0.8%, NNT = 125 for 3 years.8 Dose and cost: 60 mg daily. Daily cost: $1.56. Conclusion: Raloxifene reduced radiologic vertebral collapse in both the primary (ARR = 2.2%) and secondary prevention (ARR = 6.5%) settings, but had no effect on non-vertebral fractures (including hip fractures). Benefits for reduction in painful vertebral collapse and reduction in early breast cancer were small and of a similar magnitude to the harm of increased thromboembolic events. Ann's NOTE: Basically this report concludes that it is accurate to state that Raloxifene reduces 'painful vertebral collapse" and shows a "reduction in early breast cancer". But these benefits were "small". The downside or adverse effects were equivalent to the benefits. You decide. Arch Inter Med, 6/03 National Women's Health Network, 4/06 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.