Active ingredient: Raloxifene - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Antihypocalcemic Agents
• Osteoporosis Prophylactic
• Selective Estrogen Receptor Modulators
• Estrogen Antagonists

Dosage Forms

• Tablet

Brands / Synonyms

Evista; Keoxifene; RAL; Raloxifene Hcl; Raloxifene Hydrochloride; Raloxifeno [Spanish]; Raloxifenum [Latin]

Indications

For the prevention of osteoporosis in post-menopausal women

Pharmacology

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.

Absorption

Approximately 60% of an oral dose is absorbed, but presystemic glucuronide conjugation is extensive. Absolute bioavailability of raloxifene is 2.0%

Toxicity

Not Available

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

Contraindications

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 tablets.

Drug Interactions

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