RALOXIFENE HYDROCHLORIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Selective estrogen receptor modulator (SERM) that binds to estrogen receptors, acting as an agonist in bone and lipid metabolism and as an antagonist in breast and uterine tissues.
| Metabolism | Primarily hepatic metabolism via glucuronidation (UGT1A1, UGT1A8, UGT1A9) and minimal CYP450 involvement. Undergoes enterohepatic recirculation. |
| Excretion | Primarily fecal (biliary) elimination (approximately 60-70% as unconjugated parent drug and glucuronide conjugates); renal excretion accounts for less than 10% of the administered dose. |
| Half-life | Terminal elimination half-life is approximately 27-32 hours, supporting once-daily dosing; steady-state is achieved after 2-3 weeks. |
| Protein binding | >95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 2348 L (≈ 30 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Absolute oral bioavailability is approximately 2% due to extensive first-pass glucuronidation. |
| Onset of Action | Oral: Not applicable for acute onset; clinical effects on bone turnover markers are measurable after 4-8 weeks of continuous therapy. |
| Duration of Action | Duration of action is sustained with once-daily dosing; after discontinuation, effects on bone remodeling persist for several weeks. |
60 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR >=30 mL/min; not recommended in GFR <30 mL/min due to lack of safety data in severe renal impairment. |
| Liver impairment | Contraindicated in Child-Pugh Class C; no specific dose adjustment in Child-Pugh Class A or B, but use with caution due to limited data. |
| Pediatric use | Safety and efficacy not established; not recommended for use in pediatric patients. |
| Geriatric use | No dose adjustment required; increased risk of venous thromboembolism and stroke in elderly women, consider risk-benefit ratio. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Cholestyramine may decrease absorption Increases risk of thromboembolic events and fatal stroke.
| Breastfeeding | Raloxifene is excreted in rat milk, but no human data available. M/P ratio unknown. Due to potential adverse effects on the infant, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | Raloxifene is contraindicated in pregnancy. Based on animal studies and its anti-estrogenic mechanism, there is potential for fetal harm, including delayed ossification and embryofetal toxicity. No adequate human data exist; the drug should not be used during pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
Increased risk of venous thromboembolism (VTE) and death from stroke in women with coronary heart disease or at increased risk for major coronary events.
| Common Effects | Hot flashes |
| Serious Effects |
["Active or past history of venous thromboembolism (VTE)","Pregnancy or women who may become pregnant","Lactation (not recommended)"]
| Precautions | ["Risk of venous thromboembolism (VTE) including deep vein thrombosis and pulmonary embolism","Risk of stroke, particularly in women with coronary heart disease or risk factors","Should not be used in premenopausal women","May increase bone mineral density, but efficacy in preventing nonvertebral fractures not established","Discontinue at least 72 hours before prolonged immobilization","Use with caution in patients with hepatic impairment"] |
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| Maternal monitoring for venous thromboembolism (VTE) due to increased risk; assess for signs/symptoms of thrombosis. No specific fetal monitoring required if exposure occurs; however, confirm pregnancy status before initiation. |
| Fertility Effects | Raloxifene may impair fertility through its anti-estrogenic effects on the endometrium and ovulation. Reversible upon discontinuation. No significant effect on spermatogenesis. |