Overview
11 DESCRIPTION Raloxifene hydrochloride is an estrogen agonist/antagonist, commonly referred to as a selective estrogen receptor modulator (SERM) that belongs to the benzothiophene class of compounds. The chemical structure is: The chemical designation is methanone, [6-hydroxy-2-(4-hydroxyphenyl)benzo[ b ]thien-3-yl]-[4-[2-(1-piperidinyl)ethoxy]phenyl]-, hydrochloride.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Raloxifene is an estrogen agonist/antagonist, commonly referred to as a selective estrogen receptor modulator (SERM). The biological actions of raloxifene are largely mediated through binding to estrogen receptors. This binding results in activation of estrogenic pathways in some tissues (agonism) and blockade of estrogenic pathways in others (antagonism). The agonistic or antagonistic action of raloxifene depends on the extent of recruitment of coactivators and corepressors to estrogen receptor (ER) target gene promoters. Raloxifene appears to act as an estrogen agonist in bone. It decreases bone resorption and bone turnover, increases bone mineral density (BMD) and decreases fracture incidence.
Indications
- 1 INDICATIONS AND USAGE Raloxifene hydrochloride is an estrogen agonist/antagonist indicated for: Treatment and prevention of osteoporosis in postmenopausal women. ( 1.1 ) Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis. ( 1.2 ) Reduction in risk of invasive breast cancer in postmenopausal women at high risk for invasive breast cancer. ( 1.3 ) Important Limitations: Raloxifene hydrochloride tablets are not indicated for the treatment of invasive breast cancer, reduction of the risk of recurrence of breast cancer, or reduction of risk of noninvasive breast...
Common Doses
- 60 mg
- 1500 mg
- 2000 mg
Dosage
2 DOSAGE AND ADMINISTRATION 60 mg tablet orally once daily. (2.1) 2.1 Recommended Dosing The recommended dosage is one 60 mg raloxifene hydrochloride tablet daily, which may be administered any time of day without regard to meals [see Clinical Pharmacology (12.3) ] . For the indications in risk of invasive breast cancer the optimum duration of treatment is not known [see Clinical Studies (14.3 , 14.4) ] . 2.2 Recommendations for Calcium and Vitamin D Supplementation For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily...
Black Box Warning
WARNING: INCREASED RISK OF VENOUS THROMBOEMBOLISM AND DEATH FROM STROKE Increased risk of deep vein thrombosis and pulmonary embolism have been reported with raloxifene hydrochloride [see Warnings and Precautions (5.1) ] . Women with active or past history of venous thromboembolism should not take raloxifene hydrochloride [see Contraindications (4.1) ]. Increased risk of death due to stroke occurred in a trial in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events.
Contraindications
- 4 CONTRAINDICATIONS Active or past history of venous thromboembolism, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. (4.1) Pregnancy (4.2 , 8.1) 4.1 Venous Thromboembolism Raloxifene hydrochloride tablets are contraindicated in women with active or past history of venous thromboembolism (VTE), including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis [see Warnings and Precautions (5.1) ] . 4.2 Pregnancy Raloxifene hydrochloride is contraindicated for use in pregnancy, as it may cause fetal harm [see Use in Specific Populations (8.1) ] .
Side Effects
- 6 ADVERSE REACTIONS Adverse reactions (>2% and more common than with placebo) include: hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, sweating. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Interactions
- 7 DRUG INTERACTIONS Cholestyramine : Use with raloxifene hydrochloride is not recommended. Reduces the absorption and enterohepatic cycling of raloxifene. (7.1 , 12.3) Warfarin : Monitor prothrombin time when starting or stopping raloxifene hydrochloride. (7.2 , 12.3) Highly Protein-Bound Drugs : Use with raloxifene hydrochloride with caution. Highly protein-bound drugs include diazepam, diazoxide, and lidocaine. Raloxifene hydrochloride is more than 95% bound to plasma proteins. (7.3 , 12.3) 7.