EVISTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EVISTA (EVISTA).
Selective estrogen receptor modulator (SERM) that binds to estrogen receptors, acting as an agonist in bone and antagonist in breast and uterine tissues.
| Metabolism | Extensively metabolized in the liver via glucuronidation (UGT1A1, UGT1A8, UGT1A9) and CYP3A4-mediated oxidation. |
| Excretion | Raloxifene undergoes extensive glucuronidation; <0.1% excreted unchanged in urine. Approximately 95% is excreted in feces over 5 days (primarily as glucuronide conjugates). Renal elimination of unchanged drug is negligible (<0.1%). |
| Half-life | Terminal elimination half-life is approximately 32.5 hours (range 27-39 hours) for raloxifene and its glucuronide conjugates; clinically relevant for once-daily dosing. |
| Protein binding | >95% bound to plasma proteins, primarily albumin and α1-acid glycoprotein. |
| Volume of Distribution | Apparent Vd/F is approximately 1000-1500 L (not weight-based; extensive tissue distribution). |
| Bioavailability | Absolute oral bioavailability is approximately 2% due to extensive first-pass glucuronidation; systemic exposure is dose-proportional. |
| Onset of Action | Not directly applicable; oral therapy requires weeks for clinical effects. For bone resorption markers, reduction seen within 4-8 weeks. |
| Duration of Action | Once-daily dosing maintains steady-state effects; continuous therapy required for sustained reduction in fracture risk and LDL-cholesterol lowering. |
60 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | Contraindicated in patients with Child-Pugh Class B or C hepatic impairment. No specific dose adjustment recommended for Child-Pugh Class A, but use with caution. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment required; use standard adult dosing. Consider increased risk of venous thromboembolism and stroke in elderly women. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EVISTA (EVISTA).
| Breastfeeding | Raloxifene is excreted in rat milk; no human data available. The M/P ratio is unknown. Due to potential adverse effects on the infant, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | Pregnancy Category X. Raloxifene is contraindicated in pregnancy. In animal studies, raloxifene caused fetal abnormalities including skeletal malformations and cardiovascular defects. Human data are unavailable due to contraindication; use in pregnancy may cause fetal harm. |
| Fetal Monitoring |
■ FDA Black Box Warning
Increased risk of venous thromboembolism (VTE) and death from stroke. Not for use in women with active or history of VTE, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. Not for use in women with atrial fibrillation or other conditions that increase risk of stroke.
| Serious Effects |
Active or history of VTE, pregnancy, women who may become pregnant, lactation, hypersensitivity to raloxifene, or any component of the formulation.
| Precautions | Risk of VTE; discontinue if VTE occurs. Risk of stroke; discontinue if stroke occurs or for prolonged immobilization. May increase risk of endometrial cancer; monitor for abnormal bleeding. Not for premenopausal women. Use with caution in patients with hepatic impairment or cholestasis. May increase triglycerides; monitor in patients with history of hypertriglyceridemia. |
Loading safety data…
| Pregnancy testing before initiation and periodically during therapy in women of childbearing potential. Monitor for signs of venous thromboembolism. Discontinue if pregnancy occurs. |
| Fertility Effects | Raloxifene may impair fertility in women of childbearing potential based on animal studies showing disruption of estrous cycles and reduced fertility. Reversible upon discontinuation. In men, no significant effects noted. |