Raloxifene
Raloxifene is a selective estrogen receptor modulator (SERM) used for prevention of postmenopausal osteoporosis and reduction of invasive breast cancer risk. It activates estrogen receptors in bone while blocking them in breast and uterus, offering targeted benefit without HRT estrogenic effects.
- Chemical formula
- C28H27NO4S
- CAS number
- 84449-90-1
- ATC code
- G03XC01
- Molecular weight
- 473.59 g/mol
- Drug class
- Selective estrogen receptor modulator (SERM)
- Also known as
- Evista, Optruma
What is it?
Raloxifene is a SERM (selective estrogen receptor modulator) developed by Eli Lilly and FDA-approved as Evista in 1997 for prevention of postmenopausal osteoporosis, with treatment indication added in 1999 and breast cancer risk reduction in 2007. Authorised generic raloxifene has been widely available since 2014. Optruma is the European brand. It is on the WHO Essential Medicines List for breast cancer prevention.
Mechanism of action
Raloxifene binds estrogen receptors and produces tissue-selective effects: estrogen-agonist activity in bone (preserving bone mineral density) and on lipid metabolism (lowering LDL cholesterol), while exhibiting estrogen-antagonist activity in breast and uterine tissue (reducing breast cancer risk and not stimulating the endometrium). This selectivity is the basis of SERM positioning — capturing the bone benefits of estrogen without the breast cancer or endometrial risks.
Pharmacokinetics
Raloxifene is well absorbed orally with bioavailability of only ~2% after extensive first-pass glucuronidation; despite low bioavailability, the prolonged enterohepatic recirculation provides effective tissue concentrations. The terminal half-life is ~32 hours, supporting once-daily dosing. Raloxifene is excreted mainly in faeces. CYP3A4 metabolism is minor; few major drug interactions are reported.
Indications
Raloxifene is approved for prevention and treatment of postmenopausal osteoporosis, and for reduction of invasive breast cancer risk in postmenopausal women at increased risk. According to current osteoporosis guidelines, raloxifene is a reasonable option for postmenopausal women with osteoporosis who also have elevated breast cancer risk, although bisphosphonates remain first-line for fracture prevention. The breast cancer risk reduction is supported by the STAR and MORE trials.
Safety profile
Common adverse effects include hot flashes (paradoxically common because raloxifene is a partial estrogen agonist/antagonist), leg cramps and peripheral oedema. The most important adverse effect is venous thromboembolism, with a relative risk similar to oral estrogen HRT. According to current guidelines, raloxifene is contraindicated in women with active or prior VTE and is avoided in women at elevated VTE risk. Unlike HRT, it does not relieve menopausal symptoms and may worsen hot flashes.
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Frequently asked questions
How does raloxifene compare with bisphosphonates for osteoporosis? ▾
Bisphosphonates (alendronate, risedronate) reduce both vertebral and non-vertebral fractures by ~50%, while raloxifene reduces vertebral fractures by ~30% with less effect on hip and other non-vertebral fractures. According to current osteoporosis guidelines, bisphosphonates are first-line for most patients; raloxifene is preferred when concomitant breast cancer risk reduction is desired or when bisphosphonates are not tolerated.
Is raloxifene the same as HRT? ▾
No. Raloxifene is a SERM with tissue-selective activity — agonist in bone, antagonist in breast and uterus. HRT (estradiol or conjugated estrogens) is full estrogen agonist activity in all tissues. Raloxifene therefore prevents bone loss and reduces breast cancer risk but does not relieve hot flashes or genitourinary symptoms, and may worsen hot flashes. According to current menopause guidelines, raloxifene is not used for symptom-driven HRT.
What is the VTE risk with raloxifene? ▾
Raloxifene approximately doubles VTE risk compared with placebo, similar to oral estrogen HRT. According to the prescribing information, raloxifene is contraindicated in women with active or prior VTE, prolonged immobilisation, or elevated thrombophilic risk factors. The drug is held during prolonged immobilisation (e.g. surgical recovery) and discontinued in women with new VTE risk factors.
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