Evista

Evista

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking before taking Evista, especially:

• Anticoagulants (blood thinners) such as Coumadin (warfarin)
• Colestid (colestipol)
• Medications that contain estrogen such as hormone replacement therapy (ERT or HRT) and Lidoderm or Xylocaine (lidocaine)
• Proglycem (diazoxide)
• Questran (cholestyramine)
• Valium (diazepam)

Take Evista exactly as your doctor prescribes it. Follow the directions on your prescription label carefully. Your doctor will determine the best dose for you.

The recommended dose is one 60 mg Evista tablet daily, with or without food.

You should not use this medication if you are allergic to raloxifene, if you are pregnant or breast-feeding, or if you have ever had a blood clot.

Although it is not likely that a postmenopausal woman would be pregnant, raloxifene can cause birth defects and should not be used during pregnancy. Tell your doctor right away if you become pregnant during treatment.

Before taking raloxifene, tell your doctor if you smoke or if you have coronary artery disease, heart disease, high blood pressure, liver or kidney disease, a history of stroke or TIA, high triglycerides, if you have not gone through menopause, or if you have had breast cancer in the past.

If you need to have any type of surgery or will be on bed rest, you will need to stop taking raloxifene for at least 72 hours before your surgery or before you plan to be immobile. Any doctor or surgeon who treats you should know that you are taking raloxifene.

Avoid sitting still for long periods of time during travel while you are taking raloxifene.

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

If you take calcium supplements, do not take more than your doctor has prescribed. Taking more calcium than recommended will not provide extra protection for your bones, and may cause serious side effects including kidney stones.

Avoid sitting still for long periods of time during travel while you are taking raloxifene.

Contraindications

• Active or past episodes of venous thrombosis, including DVT, pulmonary embolism, or retinal vein thrombosis.1 52

• Women who are or may become pregnant.1

• Lactating women.1

Warnings/Precautions

Warnings

Increased risk of venous thromboembolic events (e.g., DVT, pulmonary embolism).1 55 69 72

Discontinue raloxifene ≥72 hours before and during prolonged immobilization (e.g., postsurgery recovery, prolonged bed rest); resume therapy once patient is fully ambulatory.1 52

Assess potential benefit versus risk in women at risk of thromboembolic disease secondary to CHF, superficial thrombophlebitis, or active malignancy.1 2

Increased risk for fatal stroke reported in women with CHD or increased risk for CHD (RUTH study).1 115 Assess potential benefit versus risk in women at risk of stroke secondary to history of stroke or TIA, atrial fibrillation, hypertension, or cigarette smoking.1

Not indicated for the primary or secondary prevention of cardiovascular disease.1

May cause fetal harm.1 58 59 60 61 62 63 Embryotoxic and teratogenic effects demonstrated in animals.1 60 61 If inadvertently used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1 (See Contraindications.)

General Precautions

Not indicated.1 Safety not established.1

Potential for increased serum triglyceride concentrations in women with a history of substantial hypertriglyceridemia during oral estrogen therapy; monitor serum triglycerides in these women.1

Not studied in women with a history of breast cancer.1

Investigate unexplained breast abnormality.1 Does not eliminate risk of breast cancer.1

Safety and efficacy not evaluated.1

Not associated with endometrial proliferation.1 Investigate unexplained uterine bleeding.1

Specific Populations

Category X.1 (See Fetal/Neonatal Morbidity and Mortality and also Contraindications under Cautions.)

Contraindicated.1

Not known whether raloxifene is distributed into milk.1

Not indicated.1

No substantial differences in safety, efficacy, or pharmacokinetic profile relative to younger adults.1

Use with caution; safety and efficacy not established in patients with hepatic impairment.1 (See Special Populations under Pharmacokinetics.)

Use with caution in patients with moderate to severe renal impairment; safety and efficacy not established in these patients.1 (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Hot flushes (flashes), leg cramps, peripheral edema, flu-like syndrome, arthralgia, sweating.1 2 23 69 72 88 93 96 98

Storage

Oral

20–25°C.1

• Selective estrogen receptor modulator (SERM); exhibits estrogen agonist activity on bone, but estrogen antagonist activity on breast and uterine tissue.1 2 3 4 5 6 7 8 9 13 14 15 16 17 18 21 28 69 70 88 89 101

• Differs chemically and pharmacologically from naturally occurring estrogens, synthetic steroidal and nonsteroidal compounds with estrogenic activity, and agents described as antiestrogens (e.g., clomiphene, tamoxifen, toremifene).4 13 14 15 16 17

• In postmenopausal women or women who have undergone oophorectomy, principal action in bone is to decrease the rate of bone resorption, thus slowing the rate of bone loss.1 2 3 4 5 6 7 16 17 19 20 23 37

• Inhibits estradiol-dependent proliferation of MCF-7 human mammary tumor cells in vitro.7 16 17 43 69

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis In a 21-month carcinogenicity study in mice, there was an increased incidence of ovarian tumors in female animals given 9 to 242 mg/kg, which included benign and malignant tumors of granulosa/theca cell origin and benign tumors of epithelial cell origin. Systemic exposure (AUC) of raloxifene in this group was 0.3 to 34 times that in postmenopausal women administered a 60 mg dose. There was also an increased incidence of testicular interstitial cell tumors and prostatic adenomas and adenocarcinomas in male mice given 41 or 210 mg/kg (4.7 or 24 times the AUC in humans) and prostatic leiomyoblastoma in male mice given 210 mg/kg.

In a 2-year carcinogenicity study in rats, an increased incidence in ovarian tumors of granulosa/theca cell origin was observed in female rats given 279 mg/kg (approximately 400 times the AUC in humans). The female rodents in these studies were treated during their reproductive lives when their ovaries were functional and responsive to hormonal stimulation.

Mutagenesis Raloxifene HCl was not genotoxic in any of the following test systems: the Ames test for bacterial mutagenesis with and without metabolic activation, the unscheduled DNA synthesis assay in rat hepatocytes, the mouse lymphoma assay for mammalian cell mutation, the chromosomal aberration assay in Chinese hamster ovary cells, the in vivo sister chromatid exchange assay in Chinese hamsters, and the in vivo micronucleus test in mice.

Impairment of Fertility When male and female rats were given daily doses ≥5 mg/kg (≥0.8 times the human dose based on surface area, mg/m2) prior to and during mating, no pregnancies occurred. In male rats, daily doses up to 100 mg/kg (16 times the human dose based on surface area, mg/m2) for at least 2 weeks did not affect sperm production or quality or reproductive performance. In female rats, at doses of 0.1 to 10 mg/kg/day (0.02 to 1.6 times the human dose based on surface area, mg/m2), raloxifene disrupted estrous cycles and inhibited ovulation. These effects of raloxifene were reversible. In another study in rats in which raloxifene was given during the preimplantation period at doses ≥0.1 mg/kg (≥0.02 times the human dose based on surface area, mg/m2), raloxifene delayed and disrupted embryo implantation, resulting in prolonged gestation and reduced litter size. The reproductive and developmental effects observed in animals are consistent with the estrogen receptor activity of raloxifene.

Animal Toxicology and/or Pharmacology

The skeletal effects of raloxifene treatment were assessed in ovariectomized rats and monkeys. In rats, raloxifene prevented increased bone resorption and bone loss after ovariectomy. There were positive effects of raloxifene on bone strength, but the effects varied with time. Cynomolgus monkeys were treated with raloxifene or conjugated estrogens for 2 years. In terms of bone cycles, this is equivalent to approximately 6 years in humans. Raloxifene and estrogen suppressed bone turnover and increased BMD in the lumbar spine and in the central cancellous bone of the proximal tibia. In this animal model, there was a positive correlation between vertebral compressive breaking force and BMD of the lumbar spine.

Histologic examination of bone from rats and monkeys treated with raloxifene showed no evidence of woven bone, marrow fibrosis, or mineralization defects.

These results are consistent with data from human studies of radiocalcium kinetics and markers of bone metabolism, and are consistent with the action of Evista as a skeletal antiresorptive agent.

Treatment of Postmenopausal Osteoporosis

Effect on Fracture Incidence

The effects of Evista on fracture incidence and BMD in postmenopausal women with osteoporosis were examined at 3 years in a large randomized, placebo-controlled, double-blind, multinational osteoporosis treatment trial (MORE). All vertebral fractures were diagnosed radiographically; some of these fractures also were associated with symptoms (i.e., clinical fractures). The study population consisted of 7705 postmenopausal women with osteoporosis as defined by: a) low BMD (vertebral or hip BMD at least 2.5 standard deviations below the mean value for healthy young women) without baseline vertebral fractures or b) one or more baseline vertebral fractures. Women enrolled in this study had a median age of 67 years (range 31 to 80) and a median time since menopause of 19 years.

Effect on Bone Mineral Density

Evista, 60 mg administered once daily, increased spine and hip BMD by 2 to 3%. Evista decreased the incidence of the first vertebral fracture from 4.3% for placebo to 1.9% for Evista (relative risk reduction = 55%) and subsequent vertebral fractures from 20.2% for placebo to 14.1% for Evista (relative risk reduction = 30%) (see Table 4). All women in the study received calcium (500 mg/day) and vitamin D (400 to 600 IU/day). Evista reduced the incidence of vertebral fractures whether or not patients had a vertebral fracture upon study entry. The decrease in incidence of vertebral fracture was greater than could be accounted for by increase in BMD alone.

The mean percentage change in BMD from baseline for Evista was statistically significantly greater than for placebo at each skeletal site (see Table 5).

Discontinuation from the study was required when excessive bone loss or multiple incident vertebral fractures occurred. Such discontinuation was statistically significantly more frequent in the placebo group (3.7%) than in the Evista group (1.1%).

Bone Histology

Bone biopsies for qualitative and quantitative histomorphometry were obtained at baseline and after 2 years of treatment. There were 56 paired biopsies evaluable for all indices. In Evista-treated patients, there were statistically significant decreases in bone formation rate per tissue volume, consistent with a reduction in bone turnover. Normal bone quality was maintained; specifically, there was no evidence of osteomalacia, marrow fibrosis, cellular toxicity, or woven bone after 2 years of treatment.

Effect on Endometrium

Endometrial thickness was evaluated annually in a subset of the study population (1781 patients) for 3 years. Placebo-treated women had a 0.27 mm mean decrease from baseline in endometrial thickness over 3 years, whereas the Evista-treated women had a 0.06 mm mean increase. Patients in the osteoporosis treatment study were not screened at baseline or excluded for pre-existing endometrial or uterine disease. This study was not specifically designed to detect endometrial polyps. Over the 36 months of the study, clinically or histologically benign endometrial polyps were reported in 17 of 1999 placebo-treated women, 37 of 1948 Evista-treated women, and in 31 of 2010 women treated with raloxifene HCl 120 mg/day. There was no difference between Evista- and placebo-treated women in the incidences of endometrial carcinoma, vaginal bleeding, or vaginal discharge.

Prevention of Postmenopausal Osteoporosis

The effects of Evista on BMD in postmenopausal women were examined in three randomized, placebo-controlled, double-blind osteoporosis prevention trials: (1) a North American trial enrolled 544 women; (2) a European trial, 601 women; and (3) an international trial, 619 women who had undergone hysterectomy. In these trials, all women received calcium supplementation (400 to 600 mg/day). Women enrolled in these trials had a median age of 54 years and a median time since menopause of 5 years (less than 1 year up to 15 years postmenopause). The majority of the women were White (93.5%). Women were included if they had spine BMD between 2.5 standard deviations below and 2 standard deviations above the mean value for healthy young women. The mean T scores (number of standard deviations above or below the mean in healthy young women) for the three trials ranged from -1.01 to -0.74 for spine BMD and included women both with normal and low BMD. Evista, 60 mg administered once daily, produced increases in bone mass versus calcium supplementation alone, as reflected by dual-energy x-ray absorptiometric (DXA) measurements of hip, spine, and total body BMD.

Effect on Bone Mineral Density

Compared with placebo, the increases in BMD for each of the three studies were statistically significant at 12 months and were maintained at 24 months (see Table 6). The placebo groups lost approximately 1% of BMD over 24 months.

Evista also increased BMD compared with placebo in the total body by 1.3% to 2.0% and in Ward's Triangle (hip) by 3.1% to 4.0%. The effects of Evista on forearm BMD were inconsistent between studies. In Study EU, Evista prevented bone loss at the ultradistal radius, whereas in Study NA, it did not (see Figure 1).

Figure 1: Total hip bone mineral density mean percentage change from baseline

Effect on Endometrium

In placebo-controlled osteoporosis prevention trials, endometrial thickness was evaluated every 6 months (for 24 months) by transvaginal ultrasonography (TVU). A total of 2978 TVU measurements were collected from 831 women in all dose groups. Placebo-treated women had a 0.04 mm mean increase from baseline in endometrial thickness over 2 years, whereas the Evista-treated women had a 0.09 mm mean increase. Endometrial thickness measurements in raloxifene-treated women were indistinguishable from placebo. There were no differences between the raloxifene and placebo groups with respect to the incidence of reported vaginal bleeding.

Reduction in Risk of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis

MORE Trial

The effect of Evista on the incidence of breast cancer was assessed as a secondary safety endpoint in a randomized, placebo-controlled, double-blind, multinational osteoporosis treatment trial in postmenopausal women [see Clinical Studies (14.1)]. After 4 years, Evista, 60 mg administered once daily, reduced the incidence of all breast cancers by 62%, compared with placebo (HR 0.38, 95% CI 0.22-0.67). Evista reduced the incidence of invasive breast cancer by 71%, compared with placebo (ARR 3.1 per 1000 women-years); this was primarily due to an 80% reduction in the incidence of ER-positive invasive breast cancer in the Evista group compared with placebo. Table 7 presents efficacy and selected safety outcomes.

CORE Trial

The effect of Evista on the incidence of invasive breast cancer was evaluated for 4 additional years in a follow-up study conducted in a subset of postmenopausal women originally enrolled in the MORE osteoporosis treatment trial. Women were not re-randomized; the treatment assignment from the osteoporosis treatment trial was carried forward to this study. Evista, 60 mg administered once daily, reduced the incidence of invasive breast cancer by 56%, compared with placebo (ARR 3.0 per 1000 women-years); this was primarily due to a 63% reduction in the incidence of ER-positive invasive breast cancer in the Evista group compared with placebo. There was no reduction in the incidence of ER-negative breast cancer. In the osteoporosis treatment trial and the follow-up study, there was no difference in incidence of noninvasive breast cancer between the Evista and placebo groups. Table 7 presents efficacy and selected safety outcomes.

In a subset of postmenopausal women followed for up to 8 years from randomization in MORE to the end of CORE, Evista, 60 mg administered once daily, reduced the incidence of invasive breast cancer by 60% in women assigned Evista (N=1355) compared with placebo (N=1286) (HR 0.40, 95% CI 0.21, 0.77; ARR 1.95 per 1000 women-years); this was primarily due to a 65% reduction in the incidence of ER-positive invasive breast cancer in the Evista group compared with placebo.

RUTH Trial

The effect of Evista on the incidence of invasive breast cancer was assessed in a randomized, placebo-controlled, double-blind, multinational study in 10,101 postmenopausal women at increased risk of coronary events. Women in this study had a median age of 67.6 years (range 55-92) and were followed for a median of 5.6 years (range 0.01-7.1). Eighty-four percent were White, 9.8% of women reported a first-degree relative with a history of breast cancer, and 41.4% of the women had a 5-year predicted risk of invasive breast cancer ≥1.66%, based on the modified Gail model.

Evista, 60 mg administered once daily, reduced the incidence of invasive breast cancer by 44% compared with placebo [absolute risk reduction (ARR) 1.2 per 1000 women-years]; this was primarily due to a 55% reduction in estrogen receptor (ER)-positive invasive breast cancer in the Evista group compared with placebo (ARR 1.2 per 1000 women-years). There was no reduction in ER-negative invasive breast cancer. Table 8 presents efficacy and selected safety outcomes.

The effect of Evista in reducing the incidence of invasive breast cancer was consistent among women above or below age 65 or with a 5-year predicted invasive breast cancer risk, based on the modified Gail model, <1.66%, or ≥1.66%.

Reduction in Risk of Invasive Breast Cancer in Postmenopausal Women at High Risk of Invasive Breast Cancer

STAR Trial

The effects of Evista 60 mg/day versus tamoxifen 20 mg/day over 5 years on reducing the incidence of invasive breast cancer were assessed in 19,747 postmenopausal women in a randomized, double-blind trial conducted in North America by the National Surgical Adjuvant Breast and Bowel Project and sponsored by the National Cancer Institute. Women in this study had a mean age of 58.5 years (range 35-83), a mean 5-year predicted invasive breast cancer risk of 4.03% (range 1.66-23.61%), and 9.1% had a history of lobular carcinoma in situ (LCIS). More than 93% of participants were White. As of 31 December 2005, the median time of follow-up was 4.3 years (range 0.07-6.50 years).

Evista was not superior to tamoxifen in reducing the incidence of invasive breast cancer. The observed incidence rates of invasive breast cancer were Evista 4.4 and tamoxifen 4.3 per 1000 women per year. The results from a noninferiority analysis are consistent with Evista potentially losing up to 35% of the tamoxifen effect on reduction of invasive breast cancer. The effect of each treatment on invasive breast cancer was consistent when women were compared by baseline age, history of LCIS, history of atypical hyperplasia, 5-year predicted risk of breast cancer by the modified Gail model, or the number of relatives with a history of breast cancer. Fewer noninvasive breast cancers occurred in the tamoxifen group compared to the Evista group. Table 9 presents efficacy and selected safety outcomes.

Effects on Cardiovascular Disease

In a randomized, placebo-controlled, double-blind, multinational clinical trial (RUTH) of 10,101 postmenopausal women with documented coronary heart disease or at increased risk for coronary events, no cardiovascular benefit was demonstrated after treatment with Evista 60 mg once daily for a median follow-up of 5.6 years. No significant increase or decrease was observed for coronary events (death from coronary causes, nonfatal myocardial infarction, or hospitalization for an acute coronary syndrome). An increased risk of death due to stroke after treatment with Evista was observed: 59 (1.2%) Evista-treated women died due to a stroke compared to 39 (0.8%) placebo-treated women (2.2 versus 1.5 per 1000 women-years; hazard ratio 1.49; 95% confidence interval, 1.00-2.24; p=0.0499). The incidence of stroke did not differ significantly between treatment groups (249 with Evista [4.9%] versus 224 with placebo [4.4%]; hazard ratio 1.10; 95% confidence interval 0.92-1.32; p=0.30; 9.5 versus 8.6 per 1000 women-years) [see Warnings and Precautions (5.2, 5.3)].

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.

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.

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)].

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.

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.

Literature revised December 16, 2016

Marketed by: Lilly USA, LLC
Indianapolis, IN 46285, USA

Copyright © 1997, 2016, Eli Lilly and Company. All rights reserved.

EVS-0001-USPI-20161216

Medication Guide

Evista® (Ē-VISS-tah)

(raloxifene hydrochloride tablets)
Tablets for Oral Use

Read the Medication Guide that comes with Evista before you start taking it and each time you refill your prescription. The information may have changed. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment. Talk with your doctor about Evista when you start taking it and at regular checkups.

What is the most important information I should know about Evista?

Serious and life-threatening side effects can occur while taking Evista. These include blood clots and dying from stroke:

• Increased risk of blood clots in the legs (deep vein thrombosis) and lungs (pulmonary embolism) have been reported with Evista. Women who have or have had blood clots in the legs, lungs, or eyes should not take Evista.
• Women who have had a heart attack or are at risk for a heart attack may have an increased risk of dying from stroke when taking Evista.

1. Before starting Evista, tell your doctor if you have had blood clots in your legs, lungs, or eyes, a stroke, mini-stroke (transient ischemic attack), or have an irregular heartbeat.
2. Stop taking Evista and call your doctor if you have:
   • leg pain or a feeling of warmth in the lower leg (calf).
   • swelling of the legs, hands, or feet.
   • sudden chest pain, shortness of breath, or coughing up blood.
   • sudden change in your vision, such as loss of vision or blurred vision.
3. Being still for a long time (such as sitting still during a long car or airplane trip or being in bed after surgery) can increase your risk of blood clots. (See “What should I avoid if I am taking Evista?”)

What is Evista?

Evista is a type of prescription medicine called a Selective Estrogen Receptor Modulator (SERM). Evista is for women after menopause, and has more than one use:

• Osteoporosis: Evista treats and prevents osteoporosis by helping make your bones stronger and less likely to break.
• Invasive Breast Cancer: If you have osteoporosis or are at high risk for breast cancer, Evista can be used to lower your chance of getting invasive breast cancer. Evista will not totally get rid of your chance of getting breast cancer. Your doctor can estimate your risk of breast cancer by asking you about risk factors, including:
  • your age (getting older).
  • family history of breast cancer in your mother, sister, or daughter.
  • a history of any breast biopsy, especially an abnormal biopsy.

  You and your doctor should talk about whether the possible benefit of Evista in lowering your chance of getting invasive breast cancer is greater than its possible risks.

Evista is not for use in premenopausal women (women who have not passed menopause).

Who should not take Evista?

Do not take Evista if you:

• have or have had blood clots in your legs, lungs, or eyes. Taking Evista may increase the risk of getting blood clots.
• are pregnant or could become pregnant. Evista could harm your unborn child.
• are nursing a baby. It is not known if Evista passes into breast milk or what effect it might have on the baby.

What should I tell my doctor before taking Evista?

Evista may not be right for you. Before taking Evista, tell your doctor about all your medical conditions, including if you:

• have had blood clots in your legs, lungs, or eyes, a stroke, mini-stroke (TIA/transient ischemic attack), or a type of irregular heartbeat (atrial fibrillation).
• have had breast cancer. Evista has not been fully studied in women who have a history of breast cancer.
• have liver or kidney problems.
• have taken estrogen in the past and had a high increase of triglycerides (a kind of fat in the blood).
• are pregnant, planning to become pregnant, or breast-feeding (see “Who should not take Evista?”).

Tell your doctor about all medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist each time you get a new medicine. Especially tell your doctor if you take*:

• warfarin (Coumadin®, Jantoven®)
  If you are taking warfarin or other coumarin blood thinners, your doctor may need to do a blood test when you first start or if you need to stop taking Evista. Names for this test include “prothrombin time,” “pro-time,” or “INR.” Your doctor may need to adjust the dose of your warfarin or other coumarin blood thinner.
• cholestyramine
• estrogens

Evista should not be taken with cholestyramine or estrogens.

How should I take Evista?

• Take Evista exactly how your doctor tells you to.
• Keep taking Evista for as long as your doctor prescribes it for you. It is not known how long you should keep taking Evista to lower your chance of getting invasive breast cancers.
• It is important to get your refills on time so you do not run out of the medicine.
• Take one Evista tablet each day.
• Take Evista at any time of the day, with or without food.
• To help you remember to take Evista, it may be best to take it at about the same time each day.
• Calcium and vitamin D may be taken at the same time as Evista. It is important to take calcium and vitamin D, as directed by your physician, to prevent or treat osteoporosis.
• If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take only your next regularly scheduled dose. Do not take two doses at the same time.

What should I avoid while taking Evista?

• Being still for a long time (such as during long trips or being in bed after surgery) can increase the risk of blood clots. Evista may add to this risk. If you will need to be still for a long time, talk with your doctor about ways to reduce the risk of blood clots. On long trips, move around periodically. Stop taking Evista at least 3 days before a planned surgery or before you plan on being still for a long time. You should start taking Evista again when you return to your normal activities.
• Some medicines should not be taken with Evista (see “What should I tell my doctor before taking Evista?”).

What are the possible side effects of Evista?

Serious and life-threatening side effects can occur while taking Evista. These include blood clots and dying from stroke:

• Increased risk of blood clots in the legs (deep vein thrombosis) and lungs (pulmonary embolism) have been reported with Evista. Women who have or have had blood clots in the legs, lungs, or eyes should not take Evista.
• Women who have had a heart attack or are at risk for a heart attack may have an increased risk of dying from stroke when taking Evista.

See “What is the most important information I should know about Evista?”

The most common side effects of Evista are hot flashes, leg cramps, swelling of the feet, ankles, and legs, flu syndrome, joint pain, and sweating. Hot flashes are more common during the first 6 months after starting treatment.

These are not all the side effects of Evista. Tell your doctor about any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What else should I know about Evista?

• Do not use Evista to prevent heart disease, heart attack, or strokes.
• To get the calcium and vitamin D you need, your doctor may advise you to change your diet and/or take supplemental calcium and vitamin D. Your doctor may suggest other ways to help treat or prevent osteoporosis, in addition to taking Evista and getting the calcium and vitamin D you need. These may include regular exercise, stopping smoking, and drinking less alcohol.
• Women who have hot flashes can take Evista. Evista does not treat hot flashes, and it may cause hot flashes in some women. (See “What are the possible side effects of Evista?”)
• Evista has not been found to cause breast tenderness or enlargement. If you notice any changes in your breasts, call your doctor to find out the cause. Before starting and while taking Evista you should have breast exams and mammograms, as directed by your doctor. Because Evista does not eliminate the chance of developing breast cancers, you need these examinations to find any breast cancers as early as possible.
• Evista should not cause spotting or menstrual-type bleeding. If you have any vaginal bleeding, call your doctor to find out the cause. Evista has not been found to increase the risk for cancer of the lining of the uterus.
• Women in clinical trials have taken Evista for up to eight years.

How should I store Evista?

• Store Evista at 68°F to 77°F (20°C-25°C).
• Keep Evista and all medicines out of the reach of children.

General Information about the safe and effective use of Evista

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Evista for a condition for which it was not prescribed. Do not give your Evista to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide is a summary of the most important information about Evista. If you would like more information about Evista, talk with your doctor. You can ask your doctor or pharmacist for information about Evista that is written for health professionals. For more information, call 1-800-545-5979 (toll-free).

What are the ingredients in Evista?

Active Ingredient: raloxifene hydrochloride

Inactive Ingredients: 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.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

*The brands listed are trademarks of their respective owners and are not trademarks of Eli Lilly and Company. The makers of these brands are not affiliated with and do not endorse Eli Lilly and Company or its products.

Medication Guide revised August 1, 2014

Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA

Copyright © 1997, 2014, Eli Lilly and Company. All rights reserved.

EVS-0001-MG-20140801

PACKAGE LABEL - Evista 60 mg bottle of 100 (0002-4165)

NDC 0002-4165-02

100 TABLETS

No. 4165

Evista®

raloxifene HCl

tablets 60mg

Rx only

Lilly

PACKAGE LABEL – Evista 60mg 100ct Bottle (0002-4184)

NDC 0002-4184-02

100 Tablets

No. 4165

Evista®

Raloxifene HCl tablets 60mg

Rx only

Lilly

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Common side effects of Evista include: infection, flu-like symptoms, hot flash, and sinusitis. Other side effects include: leg cramps. See below for a comprehensive list of adverse effects.

Applies to raloxifene: oral tablet

Along with its needed effects, raloxifene (the active ingredient contained in Evista) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Stop taking raloxifene and get emergency help immediately if any of the following effects occur:

• Coughing blood
• headache or migraine headache
• loss of or change in speech, coordination, or vision
• pain or numbness in chest, arm, or leg
• shortness of breath (unexplained)

Check with your doctor as soon as possible if any of the following side effects occur while taking raloxifene:

• Bloody or cloudy urine
• chest pain
• difficult, burning, or painful urination
• fever
• frequent urge to urinate
• infection, including body aches or pain, congestion in throat, cough, dryness or soreness of throat, runny nose, and loss of voice
• leg cramping
• skin rash
• swelling of hands, ankles, or feet
• vaginal itching

• Abdominal pain (severe)
• aching body pains
• congestion in lungs
• decreased vision or other changes in vision
• diarrhea
• difficulty in breathing
• hoarseness
• loss of appetite
• nausea
• trouble in swallowing
• weakness

Some side effects of raloxifene may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Hot flashes, including sudden sweating and feelings of warmth (especially common during the first 6 months of treatment)
• increased white vaginal discharge
• joint or muscle pain
• mental depression
• problems of stomach or intestines, including passing of gas, upset stomach, or vomiting
• swollen joints
• trouble in sleeping
• weight gain (unexplained)