Raloxifene and its glucuronide conjugates are interconverted by reversible metabolism and enterohepatic recycling, which prolongs the elimination half-life of raloxifene with oral administration. The medication is deconjugated into its active form in a variety of tissues, including liver, lungs, spleen, bone, uterus, and kidneys. Elimination Raloxifene is mainly excreted in bile and is eliminated in feces. Less than 0.2% of a dose is excreted unchanged in urine and less than 6% of a dose is excreted in urine as glucuronide conjugates. Chemistry Raloxifene hydrochloride has the empirical formula C28H27NO4S•HCl, which corresponds to a molecular weight of 510.05 g/mol. Raloxifene hydrochloride is an off-white to pale-yellow solid that is slightly soluble in water. Raloxifene is a benzothiophene derivative and is structurally distinct from the triphenylethylene SERMs like tamoxifen, clomifene, and toremifene. It is the only benzothiophene SERM to have been marketed. A benzothiophene SERM that was not marketed is arzoxifene (LY-353381). Bazedoxifene (Duavee, Viviant) and pipendoxifene (ERA-923) are structurally related to raloxifene but are technically not benzothiophenes and instead are indoles. History Raloxifene was approved in the United States for the prevention of postmenopausal osteoporosis in 1997, the treatment of postmenopausal osteoporosis in 1999, and to prevent or reduce the risk of breast cancer in certain postmenopausal women in 2007. It received orphan designation in 2005. Society and culture Names Raloxifene is the generic name of the drug and its and , while raloxifène is its and raloxifene hydrochloride is its , , and . It has also been known by the name keoxifene. Raloxifene is sold mainly under the brand name Evista and to a lesser extent the brand name Optruma. It is also sold under a variety of other brand names in various countries. Availability Raloxifene is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, Australia, New Zealand, South Africa, Latin America, Southern, Eastern, and Southeastern Asia, and elsewhere in the world such as in Israel and Egypt. Raloxifene is provided in the form of 60 mg oral tablets. Controversy An editorial in Lancet Oncology criticized the way that research about the medication for breast cancer prevention was released. Research Clinical studies of raloxifene for metastatic breast cancer in women have been conducted but found little effectiveness at 60 mg/day in those previously treated with tamoxifen, though modest effectiveness has been observed at higher doses. In contrast to tamoxifen,