Raloxifene

• Osteoporosis Prevention and Treatment
• Breast Cancer Risk Reduction
• Postmenopausal Bone Health

Raloxifene is a selective estrogen receptor modulator (SERM) used for prevention and treatment of postmenopausal osteoporosis and reduction of invasive breast cancer risk in high-risk postmenopausal women. It provides estrogen-like benefits for bone while acting as an estrogen antagonist in breast and uterine tissue.

Mechanism of Action

Raloxifene's tissue-selective effects result from its unique receptor interactions:

• Estrogen receptor binding: Binds to estrogen receptors (ER) alpha and beta
• Tissue-specific effects:
  • Bone: Estrogen agonist - reduces bone resorption, increases bone density
  • Breast: Estrogen antagonist - reduces breast cancer risk
  • Uterus: Neutral effect - does not stimulate endometrium
  • Lipids: Partial agonist - reduces total and LDL cholesterol

The different effects occur because the receptor-drug complex recruits different coactivators/corepressors in different tissues.

Available Formulations

Raloxifene is available as oral tablets:

• 60 mg tablets

Medical Uses

FDA-Approved Indications:

• Prevention and treatment of osteoporosis in postmenopausal women
• Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis
• Reduction in risk of invasive breast cancer in postmenopausal women at high risk

Raloxifene does not eliminate breast cancer risk and has not been shown to treat existing breast cancer.

Dosing Guidelines

All Indications:

• 60 mg once daily

Administration:

• May be taken with or without food
• Calcium and vitamin D supplementation recommended if dietary intake is inadequate

Important Safety Information

Black Box Warning:

• Increased risk of venous thromboembolism: Deep vein thrombosis and pulmonary embolism can occur
• Increased risk of death due to stroke in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events: Not indicated for cardiovascular disease risk reduction

Contraindications:

• Active or past history of venous thromboembolic events
• Pregnancy
• Breastfeeding

Warnings and Precautions:

• Discontinue at least 72 hours before prolonged immobilization (surgery, prolonged bed rest)
• Hepatic impairment: Use with caution
• Unexplained uterine bleeding: Investigate before starting
• Hypertriglyceridemia: May worsen; monitor lipids

Drug Interactions

• Cholestyramine: Reduces raloxifene absorption by 60%; avoid concurrent use
• Warfarin: May decrease warfarin effect; monitor PT/INR
• Levothyroxine: May reduce absorption; separate dosing by several hours
• Highly protein-bound drugs (diazepam, diclofenac, ibuprofen): Use with caution
• Estrogens: Not recommended to use concurrently

Special Populations

• Hepatic Impairment: Use with caution; raloxifene levels increased
• Renal Impairment: No adjustment for mild to moderate; use with caution in severe
• Premenopausal Women: Not indicated; safety not established
• Men: Not indicated
• Pregnancy: Contraindicated; Category X
• Lactation: Contraindicated