Raloxifene 💊

Related Subjects: | Osteoporosis

💡 Raloxifene is a selective oestrogen receptor modulator (SERM) - it mimics oestrogen’s protective effect on bone 🦴 while acting as an antagonist in breast and uterine tissue. ⚠️ It is not used in premenopausal women and carries a risk of venous thromboembolism (VTE).

🧠 About

• Raloxifene is an oral SERM used primarily in postmenopausal osteoporosis management.
• Acts as an oestrogen agonist in bone and lipid metabolism, but an antagonist in the uterus and breast - reducing oestrogen-related cancer risk.
• Does not stimulate the endometrium (unlike hormone replacement therapy) and may modestly lower total cholesterol and LDL.
• In postmenopausal women, it slows bone loss and reduces the risk of vertebral fractures.

⚙️ Mode of Action

• Selective binding to oestrogen receptors → tissue-specific modulation of gene transcription.
• On bone: activates oestrogen receptors on osteoblasts → inhibits osteoclast-mediated bone resorption → increases bone mineral density (BMD).
• On breast and uterus: acts as an antagonist, blocking oestrogenic proliferation signals.
• Overall effect: reduces bone turnover, preserves bone mass, and may lower breast cancer risk without increasing endometrial cancer risk.

🎯 Indications

• Prevention and treatment of postmenopausal osteoporosis.
• Alternative for women intolerant of or unsuitable for bisphosphonates or denosumab.
• Sometimes used in women at risk of both osteoporosis and oestrogen receptor–positive breast cancer.

💊 Dose and Administration

• Raloxifene 60 mg orally once daily (with or without food).
• Continue calcium and vitamin D supplementation if dietary intake is inadequate.
• Stop at least 72 hours before surgery or immobilisation due to VTE risk.

💬 Interactions

• Avoid with anion exchange resins (e.g. cholestyramine, colestipol) - markedly reduce raloxifene absorption.
• Do not use with systemic oestrogens or oestrogen-containing HRT.
• May slightly affect warfarin response - monitor INR if co-prescribed.

⚠️ Cautions

• Discontinue if VTE occurs or if prolonged immobilisation anticipated.
• Use with caution in women with a history of stroke or risk factors for arterial thromboembolism.
• Monitor lipids in those with oestrogen-induced hypertriglyceridaemia.
• Avoid in acute porphyria or active breast cancer.
• Not recommended before menopause or during pregnancy/lactation.

🚫 Contraindications

• Current or past history of venous thromboembolism (DVT, PE, retinal vein thrombosis).
• Pregnancy, lactation, or premenopausal status.
• Unexplained uterine bleeding or endometrial carcinoma.
• Severe hepatic impairment or cholestasis.

💥 Side Effects

• Common: Hot flushes, leg cramps, peripheral oedema, influenza-like symptoms.
• Vascular: Increased risk of venous thromboembolism and thrombophlebitis.
• Less common: Hypertension, migraine, rash, GI upset.
• Rare: Arterial thromboembolism, thrombocytopenia, breast discomfort.

💡 Teaching Tip

• SERMs teach students the principle of tissue-selective receptor modulation - oestrogenic in some tissues, anti-oestrogenic in others.
• Raloxifene is best remembered as the “Bone–Breast Balancer” - protects bone, blocks breast.
• Always screen for thromboembolic risk before prescribing, and discontinue during periods of immobility.

📚 References

• BNF: Raloxifene
• MHRA Drug Safety Update (2014): Venous thromboembolism risk with raloxifene
• NICE NG226 (2023): Osteoporosis: assessment and management
• Delmas PD et al., NEJM 1997;337:1641–1647 - Raloxifene reduces vertebral fractures in postmenopausal osteoporosis.