Brands, Medical Use, Clinical Data
- Antihypocalcemic Agents
- Osteoporosis Prophylactic
- Selective Estrogen Receptor Modulators
- Estrogen Antagonists
Brands / Synonyms
Evista; Keoxifene; RAL; Raloxifene Hcl; Raloxifene Hydrochloride; Raloxifeno [Spanish]; Raloxifenum [Latin]
For the prevention of osteoporosis in post-menopausal women
Raloxifene, a selective estrogen receptor modulator (SERM) of the benzothiophene class, is similar to tamoxifen in that it produces estrogen-like effects on bone and lipid metabolism, while antagonizing the effects of estrogen on mammary tissue. Raloxifene decreases bone resorption, increases bone mineral density (BMD) and decreases incidence of fractures. Raloxifene is used in the prevention of postmenopausal osteoporosis and breast cancer.
Mechanism of Action
Raloxifene binds to estrogen receptors, resulting in differential expression of multiple estrogen-regulated genes in different tissues. Raloxifene produces estrogen-like effects on bone, reducing resorption of bone and increasing bone mineral density in postmenopausal women. Raloxifene also antagonizes the effects of estrogen on mammary tissue and blocks uterotrophic responses to estrogen.
Approximately 60% of an oral dose is absorbed, but presystemic glucuronide conjugation is extensive. Absolute bioavailability of raloxifene is 2.0%
Biotrnasformation / Drug Metabolism
Hepatic, raloxifene undergoes extensive first-pass metabolism to the glucuronide conjugates: raloxifene-4'-glucuronide, raloxifene-6-glucuronide, and raloxifene-6, 4'-diglucuronide. No other metabolites have been detected, providing strong evidence that raloxifene is not metabolized by cytochrome P450 pathways
EVISTA is contraindicated in women who are or may become pregnant. EVISTA may cause fetal harm when administered
to a pregnant woman. In rabbit studies, abortion and a low rate of fetal heart anomalies (ventricular septal defects)
occurred in rabbits at doses ³ 0.1 mg/kg (³ 0.04 times
the human dose based on surface area, mg/m2), and hydrocephaly was observed in fetuses at doses
³10 mg/kg (³ 4 times the human dose based on surface
area, mg/m2). In rat studies, retardation of fetal development and developmental abnormalities (wavy ribs,
kidney cavitation) occurred at doses ³ 1mg/kg (³0.2
times the human dose based on surface area, mg/m2). Treatment of rats at doses of 0.1 to 10 mg/kg (0.02 to
1.6 times the human dose based on surface area, mg/m2) during gestation and lactation produced effects
that included delayed and disrupted parturition; decreased neonatal survival and altered physical development;
sex-and age-specific reductions in growth and changes in pituitary hormone content; and decreased lymphoid
compartment size in offspring. At 10 mg/kg, raloxifene disrupted parturition which resulted in maternal and progeny
death and morbidity. Effects in adult offspring (4 months of age) included uterine hypoplasia and reduced fertility;
however, no ovarian or vaginal pathology was observed. The patient should be apprised of the potential hazard to the
fetus if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug.
EVISTA is contraindicated in women with active or past history of venous thromboembolic events, including deep
vein thrombosis, pulmonary embolism, and retinal vein thrombosis.
EVISTA is contraindicated in women known to be hypersensitive to raloxifene or other constituents of the
Cholestyramine: Cholestyramine causes a 60% reduction in the absorption and enterohepatic cycling of
raloxifene and should not be coadministered with EVISTA.
Warfarin: The coadministration of EVISTA and warfarin has not been assessed under chronic
conditions. However, 10% decreases in prothrombin time have been observed in single-dose studies. If EVISTA is given
concurrently with warfarin, prothrombin time should be monitored.
Other Highly Protein-Bound Drugs: Raloxifene is more than 95% bound to plasma proteins. In vitro,
raloxifene did not affect the binding of warfarin, phenytoin, or tamoxifen. Caution should be used when EVISTA is
coadministered with other highly protein-bound drugs, such as clofibrate, indomethacin, naproxen, ibuprofen,
diazepam, and diazoxide.
See also CLINICAL PHARMACOLOGY, Drug-Drug Interactions