Raloxifene Hydrochloride (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- EVISTA
- RALOXIFENE HYDROCHLORIDE
Boxed Warning
Increased risk of deep vein thrombosis and pulmonary embolism have been reported with raloxifene hydrochloride [see Warnings and Precautions (5.1) ] . Women with active or past history of venous thromboembolism should not take raloxifene hydrochloride [see Contraindications (4.1) ] . Increased risk of death due to stroke occurred in a trial in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events. Consider risk-benefit balance in women at risk for stroke [see Warnings and Precautions (5.2) and Clinical Studies (14.5)] .
Mechanism of Action
Raloxifene is an estrogen agonist/antagonist, commonly referred to as a selective estrogen receptor modulator (SERM). The biological actions of raloxifene are largely mediated through binding to estrogen receptors. This binding results in activation of estrogenic pathways in some tissues (agonism) and blockade of estrogenic pathways in others (antagonism). The agonistic or antagonistic action of raloxifene depends on the extent of recruitment of coactivators and corepressors to estrogen receptor (ER) target gene promoters. Raloxifene appears to act as an estrogen agonist in bone. It decreases bone resorption and bone turnover, increases bone mineral density (BMD) and decreases fracture incidence. Preclinical data demonstrate that raloxifene is an estrogen antagonist in uterine and breast tissues. These results are consistent with findings in clinical trials, which suggest that raloxifene hydrochloride lacks estrogen-like effects on the uterus and breast tissue.
Overdosage
In an 8-week study of 63 postmenopausal women, a dose of raloxifene hydrochloride 600 mg/day was safely tolerated. In clinical trials, no raloxifene overdose has been reported. In postmarketing spontaneous reports, raloxifene overdose has been reported very rarely (less than 1 out of 10,000 [< 0.01%] patients treated). The highest overdose has been approximately 1.5 grams. No fatalities associated with raloxifene overdose have been reported. Adverse reactions were reported in approximately half of the adults who took ≥ 180 mg raloxifene hydrochloride and included leg cramps and dizziness. Two 18-month-old children each ingested raloxifene hydrochloride 180 mg. In these two children, symptoms reported included ataxia, dizziness, vomiting, rash, diarrhea, tremor, and flushing, as well as elevation in alkaline phosphatase. There is no specific antidote for raloxifene. No mortality was seen after a single oral dose in rats or mice at 5,000 mg/kg (810 times the human dose for rats and 405 times the human dose for mice based on surface area, mg/m2) or in monkeys at 1,000 mg/kg (80 times the AUC in humans).