Evista
Raloxifene hydrochloride · Tablet · Oral
Uses
1 INDICATIONS AND USAGE EVISTA ® is an estrogen agonist/antagonist indicated for: Treatment and prevention of osteoporosis in postmenopausal women. ( 1.1 ) Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis. ( 1.2 ) Reduction in risk of invasive breast cancer in postmenopausal women at high risk for invasive breast cancer. ( 1.3 ) Important Limitations: EVISTA is not indicated for the treatment of invasive breast cancer, reduction of the risk of recurrence of breast cancer, or reduction of risk of noninvasive breast cancer. ( 1.3 ) 1.1 Treatment and Prevention of Osteoporosis in Postmenopausal Women EVISTA is indicated for the treatment and prevention of osteoporosis in postmenopausal women [see Clinical Studies ( 14.1 , 14.2 )] . 1.2 Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis EVISTA is indicated for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis [see Clinical Studies ( 14.3 )] . 1.3 Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women at High Risk of Invasive Breast Cancer EVISTA is indicated for the reduction in risk of invasive breast cancer in postmenopausal women at high risk of invasive breast cancer [see Clinical Studies ( 14.4 )] . The effect in the reduction in the incidence of breast cancer was shown in a study of postmenopausal women at high risk for breast cancer with a 5-year planned duration with a median follow-up of 4.3 years [see Clinical Studies ( 14.4 )] . Twenty-seven percent of the participants received drug for 5 years. The long-term effects and the recommended length of treatment are not known. High risk of breast cancer is defined as at least one breast biopsy showing lobular carcinoma in situ (LCIS) or atypical hyperplasia, one or more first-degree relatives with breast cancer, or a 5-year predicted risk of breast cancer ≥1.66% (based on the modified Gail model). Among the factors included in the modified Gail model are the following: current age, number of first-degree relatives with breast cancer, number of breast biopsies, age at menarche, nulliparity or age of first live birth. Healthcare professionals can obtain a Gail Model Risk Assessment Tool by dialing 1-800-545-5979. Currently, no single clinical finding or test result can quantify risk of breast cancer with certainty. After an assessment of the risk of developing breast cancer, the decision regarding therapy with EVISTA should be based upon an individual assessment of the benefits and risks. EVISTA does not eliminate the risk of breast cancer. Patients should have breast exams and mammograms before starting EVISTA and should continue regular breast exams and mammograms in keeping with good medical practice after beginning treatment with EVISTA. Important Limitations of Use for Breast Cancer Risk Reduction There are no data available regarding the effect of EVISTA on invasive breast cancer incidence in women with inherited mutations (BRCA1, BRCA2) to be able to make specific recommendations on the effectiveness of EVISTA. EVISTA is not indicated for the treatment of invasive breast cancer or reduction of the risk of recurrence. EVISTA is not indicated for the reduction in the risk of noninvasive breast cancer.
Dosage and administration
60 mg tablet orally once daily. ( 2.1 ) 2.1 Recommended Dosing The recommended dosage is one 60 mg EVISTA (raloxifene hydrochloride tablets) tablet daily, which may be administered any time of day without regard to meals [see Clinical Pharmacology ( 12.3 )] . For the indications in risk of invasive breast cancer the optimum duration of treatment is not known [see Clinical Studies ( 14.3 , 14.4 )] . 2.2 Recommendations for Calcium and Vitamin D Supplementation For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. Postmenopausal women require an average of 1500 mg/day of elemental calcium. Total daily intake of calcium above 1500 mg has not demonstrated additional bone benefits while daily intake above 2000 mg has been associated with increased risk of adverse effects, including hypercalcemia and kidney stones. The recommended intake of vitamin D is 400-800 IU daily. Patients at increased risk for vitamin D insufficiency (e.g., over the age of 70 years, nursing home bound, or chronically ill) may need additional vitamin D supplements. Patients with gastrointestinal malabsorption syndromes may require higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.
Dosage forms and strengths
60 mg, white, elliptical, film-coated tablets (not scored) imprinted with 4165 on one side in edible blue ink. Tablets (not scored): 60 mg ( 3 )
Contraindications
Active or past history of venous thromboembolism, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. ( 4.1 ) Pregnancy. ( 4.2 , 8.1 ) 4.1 Venous Thromboembolism EVISTA is contraindicated in women with active or past history of venous thromboembolism (VTE), including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis [see Warnings and Precautions ( 5.1 )] . 4.2 Pregnancy EVISTA is contraindicated for use in pregnancy, as it may cause fetal harm [see Use in Specific Populations ( 8.1 )] .
Warnings and precautions
Venous Thromboembolism : Increased risk of deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. Discontinue use 72 hours prior to and during prolonged immobilization. ( 5.1 , 6.1 ) Death Due to Stroke : 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. No increased risk of stroke was seen in this trial. Consider risk-benefit balance in women at risk for stroke. ( 5.2 , 14.5 ) Cardiovascular Disease : EVISTA should not be used for the primary or secondary prevention of cardiovascular disease. ( 5.3 , 14.5 ) Premenopausal Women : Use is not recommended. ( 5.4 ) Hepatic Impairment : Use with caution. ( 5.5 ) Concomitant Use with Systemic Estrogens : Not recommended. ( 5.6 ) Hypertriglyceridemia : If previous treatment with estrogen resulted in hypertriglyceridemia, monitor serum triglycerides. ( 5.7 ) 5.1 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 [see Contraindications ( 4.1 ) and Adverse Reactions ( 6.1 )] . 5.2 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 [see Clinical Studies ( 14.5 )] . 5.3 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 [see Clinical Studies ( 14.5 )] . 5.4 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. Additionally, there is concern regarding inadvertent drug exposure in pregnancy in women of reproductive potential who become pregnant, due to risk of fetal harm [see Use in Specific Populations ( 8.1 )] . 5.5 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 [see Clinical Pharmacology ( 12.3 )] . 5.6 Concomitant Estrogen Therapy The safety of concomitant use of EVISTA with systemic estrogens has not been established and its use is not recommended. 5.7 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. 5.8 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 [see Clinical Pharmacology ( 12.3 )] . 5.9 History of Breast Cancer EVISTA has not been adequately studied in women with a prior history of breast cancer. 5.10 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. 5.11 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 [see Clinical Studies ( 14.1 , 14.2 )] . 5.12 Breast Abnormalities Any unexplained breast abnormality occurring during EVISTA therapy should be investigated. EVISTA does not eliminate the risk of breast cancer [see Clinical Studies ( 14.4 )] .
Side effects
Adverse reactions (>2% and more common than with placebo) include: hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, sweating. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-545-5979 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 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 hydrochloride (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 HCl 60 mg), and 28 (1.1%) raloxifene HCl 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 HCl (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. Table 1: Adverse Reactions Occurring in Placebo-Controlled Osteoporosis Clinical Trials at a Frequency ≥2.0% and in More EVISTA-Treated (60 mg Once Daily) Women than Placebo-Treated Women a a A: Placebo incidence greater than or equal to EVISTA incidence; B: Less than 2% incidence and more frequent with EVISTA. b Includes only patients with an intact uterus: Prevention Trials: EVISTA, n=354, Placebo, n=364; Treatment Trial: EVISTA, n=1948, Placebo, n=1999. c Actual terms most frequently referred to endometrial fluid. Treatment Prevention EVISTA (N=2557) % Placebo (N=2576) % EVISTA (N=581) % Placebo (N=584) % Body as a Whole Infection A A 15.1 14.6 Flu Syndrome 13.5 11.4 14.6 13.5 Headache 9.2 8.5 A A Leg Cramps 7.0 3.7 5.9 1.9 Chest Pain A A 4.0 3.6 Fever 3.9 3.8 3.1 2.6 Cardiovascular System Hot Flashes 9.7 6.4 24.6 18.3 Migraine A A 2.4 2.1 Syncope 2.3 2.1 B B Varicose Vein 2.2 1.5 A A Digestive System Nausea 8.3 7.8 8.8 8.6 Diarrhea 7.2 6.9 A A Dyspepsia A A 5.9 5.8 Vomiting 4.8 4.3 3.4 3.3 Flatulence A A 3.1 2.4 Gastrointestinal Disorder A A 3.3 2.1 Gastroenteritis B B 2.6 2.1 Metabolic and Nutritional Weight Gain A A 8.8 6.8 Peripheral Edema 5.2 4.4 3.3 1.9 Musculoskeletal System Arthralgia 15.5 14.0 10.7 10.1 Myalgia A A 7.7 6.2 Arthritis A A 4.0 3.6 Tendon Disorder 3.6 3.1 A A Nervous System Depression A A 6.4 6.0 Insomnia A A 5.5 4.3 Vertigo 4.1 3.7 A A Neuralgia 2.4 1.9 B B Hypesthesia 2.1 2.0 B B Respiratory System Sinusitis 7.9 7.5 10.3 6.5 Rhinitis 10.2 10.1 A A Bronchitis 9.5 8.6 A A Pharyngitis 5.3 5.1 7.6 7.2 Cough Increased 9.3 9.2 6.0 5.7 Pneumonia A A 2.6 1.5 Laryngitis B B 2.2 1.4 Skin and Appendages Rash A A 5.5 3.8 Sweating 2.5 2.0 3.1 1.7 Special Senses Conjunctivitis 2.2 1.7 A A Urogenital System Vaginitis A A 4.3 3.6 Urinary Tract Infection A A 4.0 3.9 Cystitis 4.6 4.5 3.3 3.1 Leukorrhea A A 3.3 1.7 Uterine Disorder b, c 3.3 2.3 A A Endometrial Disorder b B B 3.1 1.9 Vaginal Hemorrhage 2.5 2.4 A A Urinary Tract Disorder 2.5 2.1 A A Comparison of EVISTA and Hormone Therapy — EVISTA was compared with estrogen-progestin therapy in three clinical trials for prevention of osteoporosis. Table 2 shows adverse reactions occurring more frequently in one treatment group and at an incidence ≥2.0% in any group. Adverse reactions are shown without attribution of causality.
Drug interactions
Cholestyramine : Use with EVISTA is not recommended. Reduces the absorption and enterohepatic cycling of raloxifene. ( 7.1 , 12.3 ) Warfarin : Monitor prothrombin time when starting or stopping EVISTA. ( 7.2 , 12.3 ) Highly Protein-Bound Drugs : Use with EVISTA with caution. Highly protein-bound drugs include diazepam, diazoxide, and lidocaine. EVISTA is more than 95% bound to plasma proteins. ( 7.3 , 12.3 ) 7.1 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 [see Clinical Pharmacology ( 12.3 )] . 7.2 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 [see Clinical Pharmacology ( 12.3 )] . 7.3 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 [see Clinical Pharmacology ( 12.3 )] . 7.4 Systemic Estrogens The safety of concomitant use of EVISTA with systemic estrogens has not been established and its use is not recommended. 7.5 Other Concomitant Medications EVISTA can be concomitantly administered with ampicillin, amoxicillin, antacids, corticosteroids, and digoxin [see Clinical Pharmacology ( 12.3 )] . The concomitant use of EVISTA and lipid-lowering agents has not been studied.
Use in specific populations
Pediatric Use: Safety and effectiveness not established. ( 8.4 ) 8.1 Pregnancy Risk Summary EVISTA is contraindicated for use in pregnant women, and is not indicated for use in females of reproductive potential. Based on mechanism of action, EVISTA may block the important functions that estrogen has during all stages of pregnancy [see Clinical Pharmacology ( 12.1 )] . Limited data with EVISTA use in pregnant women are insufficient to inform any drug associated risks for births defects or miscarriage. In rabbits and rats dosed during organogenesis or during gestation and lactation, EVISTA produced multiple adverse reproductive and developmental effects, including abortion; fetal anomalies; and delayed or disrupted parturition leading to maternal and neonatal mortality, at doses less than or similar to the maximum recommended human dose (based on human body surface area comparison). Data Animal Data In the developmental and reproductive toxicity studies conducted with EVISTA, numerous adverse effects were observed in multiple animal species. In rabbits dosed during organogenesis, abortion and a low rate of fetal heart anomalies (ventricular septal defects) occurred at doses ≥0.1 mg/kg (≥0.04 times the human dose based on surface area, mg/m 2 ). In rats dosed during organogenesis, retardation of fetal growth and developmental abnormalities (wavy ribs, kidney cavitation) occurred at doses ≥1 mg/kg (≥0.2 times the human dose based on surface area, mg/m 2 ). Treatment of rats during gestation and lactation with doses of 0.1 to 10 mg/kg (0.02 to 1.6 times the human dose based on surface area, mg/m 2 ) produced effects that included delayed and disrupted parturition, decreased neonatal survival and altered physical development, sex- and age-specific reductions in growth and changes in pituitary hormone content, and decreased lymphoid compartment size in offspring. At 10 mg/kg, the disruption of parturition resulted in maternal and progeny morbidity and death. Effects in adult offspring (4 months of age) included uterine hypoplasia and reduced fertility; however, no ovarian or vaginal pathology was observed. 8.2 Lactation Risk Summary EVISTA is not indicated for use in females of reproductive potential. There is no information on the presence of raloxifene in human milk, the effects on the breastfed child, or the effects on milk production. However, based on mechanism of action, EVISTA may block the important functions that estrogen has in mammary tissue during lactation [see Clinical Pharmacology ( 12.1 )] . 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of patients in placebo-controlled clinical studies of EVISTA, 61% were 65 and over, while 15.5% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Based on clinical trials, there is no need for dose adjustment for geriatric patients [see Clinical Pharmacology ( 12.3 )] . 8.6 Renal Impairment EVISTA should be used with caution in patients with moderate or severe renal impairment [see Warnings and Precautions ( 5.8 ) and Clinical Pharmacology ( 12.3 )] . 8.7 Hepatic Impairment EVISTA should be used with caution in patients with hepatic impairment [see Warnings and Precautions ( 5.5 ) and Clinical Pharmacology ( 12.3 )] .
Pregnancy
8.1 Pregnancy Risk Summary EVISTA is contraindicated for use in pregnant women, and is not indicated for use in females of reproductive potential. Based on mechanism of action, EVISTA may block the important functions that estrogen has during all stages of pregnancy [see Clinical Pharmacology ( 12.1 )] . Limited data with EVISTA use in pregnant women are insufficient to inform any drug associated risks for births defects or miscarriage. In rabbits and rats dosed during organogenesis or during gestation and lactation, EVISTA produced multiple adverse reproductive and developmental effects, including abortion; fetal anomalies; and delayed or disrupted parturition leading to maternal and neonatal mortality, at doses less than or similar to the maximum recommended human dose (based on human body surface area comparison). Data Animal Data In the developmental and reproductive toxicity studies conducted with EVISTA, numerous adverse effects were observed in multiple animal species. In rabbits dosed during organogenesis, abortion and a low rate of fetal heart anomalies (ventricular septal defects) occurred at doses ≥0.1 mg/kg (≥0.04 times the human dose based on surface area, mg/m 2 ). In rats dosed during organogenesis, retardation of fetal growth and developmental abnormalities (wavy ribs, kidney cavitation) occurred at doses ≥1 mg/kg (≥0.2 times the human dose based on surface area, mg/m 2 ). Treatment of rats during gestation and lactation with doses of 0.1 to 10 mg/kg (0.02 to 1.6 times the human dose based on surface area, mg/m 2 ) produced effects that included delayed and disrupted parturition, decreased neonatal survival and altered physical development, sex- and age-specific reductions in growth and changes in pituitary hormone content, and decreased lymphoid compartment size in offspring. At 10 mg/kg, the disruption of parturition resulted in maternal and progeny morbidity and death. Effects in adult offspring (4 months of age) included uterine hypoplasia and reduced fertility; however, no ovarian or vaginal pathology was observed.
Pediatric use
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use Of the total number of patients in placebo-controlled clinical studies of EVISTA, 61% were 65 and over, while 15.5% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Based on clinical trials, there is no need for dose adjustment for geriatric patients [see Clinical Pharmacology ( 12.3 )] .
Overdosage
In an 8-week study of 63 postmenopausal women, a dose of raloxifene hydrochloride (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 HCl and included leg cramps and dizziness. Two 18-month-old children each ingested raloxifene HCl 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/m 2 ) or in monkeys at 1000 mg/kg (80 times the AUC in humans).
Description
(raloxifene hydrochloride) is an estrogen agonist/antagonist, commonly referred to as a selective estrogen receptor modulator (SERM) that belongs to the benzothiophene class of compounds. The chemical structure is: The chemical designation is methanone, [6-hydroxy-2-(4-hydroxyphenyl)benzo[ b ]thien-3-yl]-[4-[2-(1-piperidinyl)ethoxy]phenyl]-, hydrochloride. Raloxifene hydrochloride (HCl) has the empirical formula C 28 H 27 NO 4 S
• HCl, which corresponds to a molecular weight of 510.05. Raloxifene HCl is an off-white to pale-yellow solid that is very slightly soluble in water. EVISTA is supplied in a tablet dosage form for oral administration. Each EVISTA tablet contains 60 mg of raloxifene HCl, which is the molar equivalent of 55.71 mg of free base. Inactive ingredients include anhydrous lactose, carnauba wax, crospovidone, FD&C Blue No. 2 aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, modified pharmaceutical glaze, polyethylene glycol, polysorbate 80, povidone, propylene glycol, and titanium dioxide. Chemical Structure
Mechanism of action
12.1 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 EVISTA lacks estrogen-like effects on the uterus and breast tissue.
How supplied
16.1 How Supplied EVISTA 60 mg tablets are white, elliptical, film coated (not scored) and imprinted with 4165 on one side in edible blue ink. They are available as follows: Presentation and NDC Bottles of 30 (unit of use) 0002-4184-30 16.2 Storage and Handling Store at controlled room temperature, 20° to 25°C (68° to 77°F) [ see USP]. The USP defines controlled room temperature as a temperature maintained thermostatically that encompasses the usual and customary working environment of 20° to 25°C (68° to 77°F); that results in a mean kinetic temperature calculated to be not more than 25°C; and that allows for excursions between 15° and 30°C (59° and 86°F) that are experienced in pharmacies, hospitals, and warehouses. 16.1 How Supplied EVISTA 60 mg tablets are white, elliptical, film coated (not scored) and imprinted with 4165 on one side in edible blue ink. They are available as follows: Presentation and NDC Bottles of 30 (unit of use) 0002-4184-30
Storage
16.2 Storage and Handling Store at controlled room temperature, 20° to 25°C (68° to 77°F) [ see USP]. The USP defines controlled room temperature as a temperature maintained thermostatically that encompasses the usual and customary working environment of 20° to 25°C (68° to 77°F); that results in a mean kinetic temperature calculated to be not more than 25°C; and that allows for excursions between 15° and 30°C (59° and 86°F) that are experienced in pharmacies, hospitals, and warehouses.
Patient information
See FDA-approved Medication Guide. Physicians should instruct their patients to read the Medication Guide before starting therapy with EVISTA and to reread it each time the prescription is renewed. 17.1 Osteoporosis Recommendations, Including Calcium and Vitamin D Supplementation For osteoporosis treatment or prevention, patients should be instructed to take supplemental calcium and/or vitamin D if intake is inadequate. Patients at increased risk for vitamin D insufficiency (e.g., over the age of 70 years, nursing home bound, chronically ill, or with gastrointestinal malabsorption syndromes) should be instructed to take additional vitamin D if needed. Weight-bearing exercises should be considered along with the modification of certain behavioral factors, such as cigarette smoking and/or excessive alcohol consumption, if these factors exist. 17.2 Patient Immobilization EVISTA should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest), and patients should be advised to avoid prolonged restrictions of movement during travel because of the increased risk of venous thromboembolic events [see Warnings and Precautions ( 5.1 )] . 17.3 Hot Flashes or Flushes EVISTA may increase the incidence of hot flashes and is not effective in reducing hot flashes or flushes associated with estrogen deficiency. In some asymptomatic patients, hot flashes may occur upon beginning EVISTA therapy. 17.4 Reduction in Risk of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis or at High Risk of Invasive Breast Cancer Use of EVISTA is associated with the reduction of the risk of invasive breast cancer in postmenopausal women. EVISTA has not been shown to reduce the risk of noninvasive breast cancer. When considering treatment, physicians need to discuss the potential benefits and risks of EVISTA treatment with the patient. EVISTA is not indicated for the treatment of invasive breast cancer or reduction of the risk of recurrence. Patients should have breast exams and mammograms before starting EVISTA and should continue regular breast exams and mammograms in keeping with good medical practice after beginning treatment with EVISTA. Marketed by: Lilly USA, LLC Indianapolis, IN 46285, USA Copyright © 1997, 2023, Eli Lilly and Company. All rights reserved. EVS-0005-USPI-20230306
Label text from the FDA structured product label by Eli Lilly and Company (revised Feb 11, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Raloxifene Hydrochloride in 1 product
Evista NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0002-4184 | Raloxifene Hydrochloride 60 mg/1 Tablet | Eli Lilly and Company | NDA |
Frequently asked questions
What is Evista used for?
1 INDICATIONS AND USAGE EVISTA ® is an estrogen agonist/antagonist indicated for: Treatment and prevention of osteoporosis in postmenopausal women. ( 1.1 ) Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis. ( 1.2 ) Reduction in risk of invasive breast cancer in postmenopausal women at high risk for invasive breast cancer. ( 1.3 ) Important Limitations: EVISTA…
What are the side effects of Evista?
Adverse reactions (>2% and more common than with placebo) include: hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, sweating. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-545-5979 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions,… See the full label for the complete list.
Who makes Evista?
Evista is listed by 1 labeler in the FDA NDC directory, including Eli Lilly and Company.