Evista

/ Eli Lilly

The recommended dosage is one 60 mg EVISTA tablet daily, which may be administered any time of day without regard to meals.
For full details see prescribing information.

Treatment and Prevention of Osteoporosis in Postmenopausal Women, Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis and reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women at High Risk of Invasive Breast Cancer.

Venous Thromboembolism, Pregnancy, Women Who May Become Pregnant, and Nursing Mothers.

INCREASED RISK OF VENOUS THROMBOEMBOLISM AND DEATH FROM STROKE
Increased risk of deep vein thrombosis and pulmonary embolism have been reported with EVISTA. Women with active or past history of venous thromboembolism should not take EVISTA .
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
Venous Thromboembolism: In clinical trials, EVISTA-treated women had an increased risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism). Other venous thromboembolic events also could occur. A less serious event, superficial thrombophlebitis, also has been reported more frequently with EVISTA than with placebo. The greatest risk for deep vein thrombosis and pulmonary embolism occurs during the first 4 months of treatment, and the magnitude of risk appears to be similar to the reported risk associated with use of hormone therapy. Because immobilization increases the risk for venous thromboembolic events independent of therapy, EVISTA should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest), and EVISTA therapy should be resumed only after the patient is fully ambulatory. In addition, women taking EVISTA should be advised to move about periodically during prolonged travel. The risk-benefit balance should be considered in women at risk of thromboembolic disease for other reasons, such as congestive heart failure, superficial thrombophlebitis, and active malignancy.
Death Due to Stroke: In a clinical trial of postmenopausal women with documented coronary heart disease or at increased risk for coronary events, an increased risk of death due to stroke was observed after treatment with EVISTA. During an average follow-up of 5.6 years, 59 (1.2%) EVISTA-treated women died due to a stroke compared to 39 (0.8%) placebo-treated women (22 versus 15 per 10,000 women-years; hazard ratio 1.49; 95% confidence interval, 1.00-2.24; p=0.0499). There was no statistically significant difference between treatment groups in the incidence of stroke (249 in EVISTA [4.9%] versus 224 placebo [4.4%]). EVISTA had no significant effect on all-cause mortality. The risk-benefit balance should be considered in women at risk for stroke, such as prior stroke or transient ischemic attack (TIA), atrial fibrillation, hypertension, or cigarette smoking.
Cardiovascular Disease: EVISTA should not be used for the primary or secondary prevention of cardiovascular disease. In a clinical trial of postmenopausal women with documented coronary heart disease or at increased risk for coronary events, no cardiovascular benefit was demonstrated after treatment with raloxifene for 5 years.
Premenopausal Use: There is no indication for premenopausal use of EVISTA. Safety of EVISTA in premenopausal women has not been established and its use is not recommended.
Hepatic Impairment: EVISTA should be used with caution in patients with hepatic impairment. Safety and efficacy have not been established in patients with hepatic impairment.
Concomitant Estrogen Therapy: The safety of concomitant use of EVISTA with systemic estrogens has not been established and its use is not recommended.
History of Hypertriglyceridemia when Treated with Estrogens: Limited clinical data suggest that some women with a history of marked hypertriglyceridemia (>5.6 mmol/L or >500 mg/dL) in response to treatment with oral estrogen or estrogen plus progestin may develop increased levels of triglycerides when treated with EVISTA. Women with this medical history should have serum triglycerides monitored when taking EVISTA.
Renal Impairment: EVISTA should be used with caution in patients with moderate or severe renal impairment. Safety and efficacy have not been established in patients with moderate or severe renal impairment.
History of Breast Cancer: EVISTA has not been adequately studied in women with a prior history of breast cancer.
Use in Men: There is no indication for the use of EVISTA in men. EVISTA has not been adequately studied in men and its use is not recommended.
Unexplained Uterine Bleeding: Any unexplained uterine bleeding should be investigated as clinically indicated. EVISTA-treated and placebo-treated groups had similar incidences of endometrial proliferation.
Breast Abnormalities: Any unexplained breast abnormality occurring during EVISTA therapy should be investigated. EVISTA does not eliminate the risk of breast cancer. For full details see prescribing information.

Clinical Trials Experience: Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to EVISTA in 8429 patients who were enrolled in placebo-controlled trials, including 6666 exposed for 1 year and 5685 for at least 3 years.
Osteoporosis Treatment Clinical Trial (MORE) — The safety of raloxifene in the treatment of osteoporosis was assessed in a large (7705 patients) multinational, placebo-controlled trial. Duration of treatment was 36 months, and 5129 postmenopausal women were exposed to raloxifene (2557 received 60 mg/day, and 2572 received 120 mg/day). The incidence of all-cause mortality was similar among groups: 23 (0.9%) placebo, 13 (0.5%) EVISTA-treated (raloxifene 60 mg), and 28 (1.1%) raloxifene 120 mg women died. Therapy was discontinued due to an adverse reaction in 10.9% of EVISTA-treated women and 8.8% of placebo-treated women. Venous Thromboembolism: The most serious adverse reaction related to EVISTA was VTE (deep venous thrombosis, pulmonary embolism, and retinal vein thrombosis). During an average of study-drug exposure of 2.6 years, VTE occurred in about 1 out of 100 patients treated with EVISTA. Twenty-six EVISTA-treated women had a VTE compared to 11 placebo-treated women, the hazard ratio was 2.4 (95% confidence interval, 1.2, 4.5), and the highest VTE risk was during the initial months of treatment.
Common adverse reactions considered to be related to EVISTA therapy were hot flashes and leg cramps. Hot flashes occurred in about one in 10 patients on EVISTA and were most commonly reported during the first 6 months of treatment and were not different from placebo thereafter. Leg cramps occurred in about one in 14 patients on EVISTA.
Placebo-Controlled Osteoporosis Prevention Clinical Trials — The safety of raloxifene has been assessed primarily in 12 Phase 2 and Phase 3 studies with placebo, estrogen, and estrogen-progestin therapy control groups. The duration of treatment ranged from 2 to 30 months, and 2036 women were exposed to raloxifene (371 patients received 10 to 50 mg/day, 828 received 60 mg/day, and 837 received from 120 to 600 mg/day). Therapy was discontinued due to an adverse reaction in 11.4% of 581 EVISTA-treated women and 12.2% of 584 placebo-treated women. Discontinuation rates due to hot flashes did not differ significantly between EVISTA and placebo groups (1.7% and 2.2%, respectively).
Common adverse reactions considered to be drug-related were hot flashes and leg cramps. Hot flashes occurred in about one in four patients on EVISTA versus about one in six on placebo. The first occurrence of hot flashes was most commonly reported during the first 6 months of treatment. Table 1 lists adverse reactions occurring in either the osteoporosis treatment or in five prevention placebo-controlled clinical trials at a frequency ≥2.0% in either group and in more EVISTA-treated women than in placebo-treated women. Adverse reactions are shown without attribution of causality. The majority of adverse reactions occurring during the studies were mild and generally did not require discontinuation of therapy. Hot flashes and leg cramps. For full details see prescribing information.

Cholestyramine Concomitant administration of cholestyramine with EVISTA is not recommended. Although not specifically studied, it is
anticipated that other anion exchange resins would have a similar effect. EVISTA should not be co-administered with other anion exchange resins.
Warfarin If EVISTA is given concomitantly with warfarin or other warfarin derivatives, prothrombin time should be monitored more closely when starting or stopping therapy with EVISTA.
Other Highly Protein-Bound Drugs EVISTA should be used with caution with certain other highly protein-bound drugs such as diazepam, diazoxide, and lidocaine. Although not examined, EVISTA might affect the protein binding of other drugs. Raloxifene is more than 95% bound to plasma proteins.
Systemic Estrogens The safety of concomitant use of EVISTA with systemic estrogens has not been established and its use is not recommended.
Other Concomitant Medications EVISTA can be concomitantly administered with ampicillin, amoxicillin, antacids, corticosteroids, and digoxin.
The concomitant use of EVISTA and lipid-lowering agents has not been studied.
For full details see prescribing information.

Pregnancy: Pregnancy Category X. EVISTA should not be used in women who are or may become pregnant.
Nursing Mothers: EVISTA should not be used by lactating women. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when raloxifene is administered to a nursing woman.
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
For full details see prescribing information.

In an 8-week study of 63 postmenopausal women, a dose of raloxifene HCl 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 and included leg cramps and dizziness. Two 18-month-old children each ingested raloxifene 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 5000 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 1000 mg/kg (80 times the AUC in humans).