What is the use of Evista (raloxifene) in postmenopausal women?

Evista (Raloxifene) in Postmenopausal Women

Evista (raloxifene) 60 mg daily is FDA-approved for three specific indications in postmenopausal women: treatment and prevention of osteoporosis, reduction of invasive breast cancer risk in women with osteoporosis, and reduction of invasive breast cancer risk in high-risk women. 1

Primary FDA-Approved Indications

Osteoporosis Management

• Raloxifene 60 mg daily is indicated for both prevention and treatment of osteoporosis in postmenopausal women, demonstrating significant increases in bone mineral density at the lumbar spine (2.1-3.4%), femoral neck (0.9-2.3%), and total hip (1.0-2.3%) compared to placebo over 12-36 months. 1, 2, 3
• The medication reduces vertebral fracture risk by 30-55% in women with osteoporosis, with the greatest benefit (55% reduction) seen in women without prevalent baseline fractures and 31-49% reduction in those with existing fractures. 2, 4
• Raloxifene has NOT been proven to reduce hip fractures or other non-vertebral fractures, which is a critical limitation compared to bisphosphonates like alendronate and risedronate. 5, 4

Breast Cancer Risk Reduction

• Raloxifene reduces invasive breast cancer risk by 65-76% in postmenopausal women with osteoporosis, with a 90% reduction specifically for estrogen receptor-positive invasive breast cancers. 2, 3, 6
• The medication is indicated for high-risk postmenopausal women, defined as those with at least one breast biopsy showing LCIS or atypical hyperplasia, one or more first-degree relatives with breast cancer, or a 5-year predicted risk ≥1.66% based on the modified Gail model. 1
• Raloxifene does NOT reduce estrogen receptor-negative breast cancer risk and is NOT indicated for treating established invasive breast cancer, preventing recurrence, or reducing noninvasive breast cancer risk. 1, 3

Dosing and Duration

• The standard dose is 60 mg orally once daily, taken at any time of day without regard to meals. 1
• For breast cancer risk reduction alone, the standard duration is 5 years. 5, 7
• Raloxifene may be used beyond 5 years when osteoporosis treatment is the primary indication, with breast cancer risk reduction as a secondary benefit, supported by 8-year safety data showing no increase in mortality. 7

Absolute Contraindications

Raloxifene is absolutely contraindicated in the following situations: 5, 1

• Active or past history of venous thromboembolism (deep vein thrombosis or pulmonary embolism)
• History of stroke or transient ischemic attack
• Prolonged immobilization (discontinue at least 72 hours before anticipated immobilization)
• Premenopausal women
• Pregnancy

Critical Safety Warnings

Venous Thromboembolism Risk

• Raloxifene carries a BLACK BOX WARNING for increased risk of deep vein thrombosis and pulmonary embolism, with a relative risk of 3.1 compared to placebo (0.7% vs 0.2% for DVT; 0.3% vs 0.1% for PE). 1, 2, 3
• Monitor particularly during the first 4 months of therapy and discontinue 72 hours before prolonged immobilization. 7

Stroke Mortality Risk

• Raloxifene carries a BLACK BOX WARNING for increased risk of death from stroke, observed in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events. 1

Common Adverse Effects

• Hot flashes and leg cramps are the most common side effects, occurring more frequently than with placebo but significantly less than with hormone replacement therapy. 5, 2, 3
• Raloxifene does NOT cause vaginal bleeding (reported in <6.4% vs 50-88% with hormone replacement therapy) and has no stimulatory effects on the endometrium. 3

Comparison to Alternative Therapies

Raloxifene vs. Bisphosphonates for Osteoporosis

• For vertebral fracture prevention, raloxifene is effective but bisphosphonates (alendronate, risedronate) are superior because they also reduce hip and non-vertebral fractures. 5
• Choose raloxifene over bisphosphonates when breast cancer risk reduction is a concurrent goal in postmenopausal women with osteoporosis. 5

Raloxifene vs. Tamoxifen for Breast Cancer Risk Reduction

• Raloxifene is as effective as tamoxifen in reducing invasive breast cancer risk in postmenopausal women, with no significant difference between the two agents. 6, 4
• Raloxifene has a superior safety profile compared to tamoxifen, with significantly lower risks of thromboembolic disease, benign uterine complaints, cataracts, and endometrial cancer. 5, 7
• Raloxifene should NOT be used after tamoxifen therapy due to cross-resistance and concerns about limited activity against advanced breast cancer following tamoxifen exposure. 5
• Raloxifene and tamoxifen should NEVER be used concurrently, as there is no evidence supporting combined use and guidelines explicitly recommend against this combination. 8

Clinical Decision Algorithm

For postmenopausal women requiring osteoporosis therapy:

• If primary concern is hip fracture prevention → Choose bisphosphonates (alendronate or risedronate) 5
• If vertebral fracture prevention is the goal AND patient has elevated breast cancer risk → Choose raloxifene 60 mg daily 5, 1
• If patient has contraindications to raloxifene (history of VTE, stroke, TIA) → Choose bisphosphonates 5

For postmenopausal women at high risk for breast cancer:

• If postmenopausal with osteoporosis or high breast cancer risk → Choose raloxifene 60 mg daily for 5 years 5, 1
• If premenopausal → Raloxifene is contraindicated; consider tamoxifen instead 5
• If history of tamoxifen use → Do NOT use raloxifene due to cross-resistance 5, 8

Important Limitations

• Raloxifene has no proven efficacy in women with BRCA1 or BRCA2 mutations. 1
• Patients must continue regular breast exams and mammograms, as raloxifene does not eliminate breast cancer risk. 1
• The optimum duration of treatment for breast cancer risk reduction beyond 5 years is unknown. 1