Generic Name

Raloxifene

Mechanism

• Raloxifene is a selective estrogen receptor modulator (SERM).
• Bone: Acts as an estrogen agonist at osteoblastic ERβ receptors → ↑ bone formation, ↓ resorption.
• Breast: Exerts an antagonist effect on breast ERα → ↓ ductal epithelial proliferation, reducing breast cancer risk.
• Uterus: Minimal uterine estrogen activity → does not stimulate endometrial proliferation, decreasing endometrial cancer risk.
• Lipid profile: Lowers LDL and VLDL while modestly raising HDL.

Pharmacokinetics

• Route & Absorption: Oral; rapid absorption, peak concentration ~2–4 h post‑dose.
• Bioavailability: 16–23 % (food reduces absorption by ~20 %).
• Distribution: Highly protein‑bound (~99 %).
• Metabolism: Hepatic via CYP3A4 → multiple metabolites (mostly inactive).
• Excretion: Primarily biliary; minor renal clearance.
• Half‑life: Approx. 27 h, allowing once‑daily dosing.
• Drug interactions:
• CYP3A4 inducers (e.g., rifampin) reduce plasma levels.
• Strong CYP3A4 inhibitors may increase concentration but no dose adjustment required.
• Avoid concomitant use with anticonvulsants that alter estrogen metabolism.

Indications

*Not indicated for men, pre‑menopausal women, or patients with a history of thromboembolic disease.*

Contraindications

• Contraindications
• History of venous thromboembolism (VTE) or hypercoagulable states.
• Active liver disease or unexplained abnormal LFTs.
• Known hypersensitivity to raloxifene or any excipients.
• Pregnancy or lactation.
• Warnings
• VTE risk: 1–2 % risk of DVT/PE; patients should have negative DVT screening before initiation.
• Hot flashes & flushing: Common but predict therapy adherence.
• Contraception: Use reliable contraception; raloxifene is teratogenic.
• Liver toxicity: Rare transaminase elevations; monitor LFTs periodically.

Dosing

• Adult females (≥50 y): 60 mg orally once daily (take same time each day).
• Administration guidelines
• Take with a full glass of water, preferably on an empty stomach.
• Food may reduce absorption; maintain consistent meal patterns.
• Avoid alcohol; patients should limit intake to moderate levels.
• Missed dose: If missed within 24 h, take immediately; if >24 h, skip and resume next day.

Adverse Effects

• Common (≥1 % frequency)
• Hot flashes
• Leg cramps
• Mild nausea
• Constipation
• Fatigue
• Serious (≤1 % frequency)
• Deep vein thrombosis (DVT) / pulmonary embolism (PE)
• Liver injury (transaminitis)
• Cholelithiasis
• Severe vasomotor symptoms (rare)
• Lower limb ischemia (extremely rare)

Monitoring

• Baseline:
• CBC, CMP, LFTs, fasting lipid panel.
• BMD via DXA scan (baseline and 1‑yr follow‑up).
• DVT evaluation if risk factors present.
• Ongoing:
• Annual LFTs 1–6 months after initiation; repeat if abnormal.
• Monitor for VTE symptoms; educate patients on red‑flag signs (leg swelling, chest pain, dyspnea).
• Reassess BMD every 12–24 months.
• Continue cancer surveillance (mammography per guidelines).

Clinical Pearls

• VTE is the most significant safety signal. Prioritize thorough VTE risk assessment before prescribing.
• Prefer Raloxifene over estrogen in women with a history of estrogen‑sensitive breast lesions; it lowers breast cancer risk while** reducing vaginal bleeding.
• Because of limited neuropsychological impact, it is less likely to worsen osteoarthritis pain than some other bone‑active agents; good for patients with concurrent hip arthropathy.
• Not metabolically active in men. Use of Raloxifene for male osteoporosis is off‑label and unsupported; alternative agents (e.g., denosumab, bisphosphonates) are preferred.
• Administering with a small snack may improve tolerability in patients sensitive to gastrointestinal upset while maintaining therapeutic absorption (~20 % reduction).
• Adherence hinges on dosing simplicity: a once‑daily 60‑mg tablet is well‑tolerated in 93 % of post‑menopausal women in clinical trials.

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• Note: This drug card is for educational purposes. Always consult current prescribing information, institutional protocols, and patient‑specific factors before initiating therapy.