Safety Profile

• Demonstrated Safety Profile
• Safety Information and Boxed Warning
• Venous Thromboembolic Event (VTE) Facts

Demonstrated Safety Profile
In clinical trials, up to 8 years of clinical research^1,2 and more than 37,000 patients^3-5 demonstrate the safety profile of EVISTA. Selective estrogen receptor modulators (SERMs), like EVISTA, may act differently in various tissues and organs. EVISTA appears to act like an estrogen agonist in the bones and an estrogen antagonist in the breast and uterus.

EVISTA has shown:

• No increased risk for endometrial hyperplasia, uterine cancer or ovarian cancer in clinical trials vs placebo¹

Select Gynecologic Outcomes From the 8 Years of MORE-CORE

• There was no difference between EVISTA - and placebo-treated women in the incidences of endometrial carcinoma, vaginal bleeding, or vaginal discharge

Indications for EVISTA

EVISTA^® (raloxifene HCl tablets) is indicated for the treatment of osteoporosis and for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis.

Important limitations of use for breast cancer risk reduction are as follows: 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, and EVISTA is not indicated for the reduction in the risk of noninvasive breast cancer.

Important Safety Information

Contraindications

• EVISTA is contraindicated in nursing women and in women who are or may become pregnant, as it may cause fetal harm. EVISTA is also contraindicated in women with active or past venous thromboembolic events (VTEs), including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis.

Warnings and Precautions

• In a study of postmenopausal women at high risk for cardiovascular disease taking EVISTA, there was no increase in the incidence of stroke; however, there was an increase in death due to stroke. EVISTA also did not increase or decrease the incidence of overall mortality, cardiovascular mortality, or heart attack. The risk-benefit balance should be considered in women at risk for stroke, such as those with prior stroke or transient ischemic attack (TIA), atrial fibrillation, hypertension, or cigarette smoking.
• EVISTA should be used with caution in patients with hepatic impairment or moderate/severe renal impairment since safety and efficacy have not been established in these patients.
• The safety of concomitant use of EVISTA with systemic estrogens has not been established and its use is not recommended.

Adverse Reactions

• The common adverse reactions considered to be drug related:

• Adverse reactions occurring in the clinical trials at a frequency ≥2.0% in either group and in more EVISTA-treated women than in placebo-treated women include:

• The majority of adverse reactions occurring during the osteoporosis prevention and treatment studies were mild and generally did not require discontinuation of therapy.

For additional information, please see full Prescribing Information and Medication Guide.

Venous Thromboembolic Event (VTE) Facts
A venous thromboembolic event, such as deep vein thrombosis (DVT) or pulmonary embolism (PE), is a blood clot that originates in the veins. It is not a blood clot that originates in the arterial system.

The combined annual incidence rate of DVT and PE in women in the United States*^,†,7

VTE data from the MORE clinical trial^†:

• The most serious adverse reaction to EVISTA was VTE
• During an average study drug exposure of 2.6 years, VTE occurred in about 1 out of 100 patients treated with EVISTA. Highest VTE risk was observed during the first few months of therapy
• Twenty-six women treated with EVISTA had a VTE compared with 11 placebo-treated women. The hazard ratio was 2.4 (95% CI 1.2; 4.5)
• EVISTA increased the risk of venous thromboembolism to 2- to 3- fold over placebo in postmenopausal women with osteoporosis whose average age was 67 years^8,9

^†Multiple Outcomes of Raloxifene Evaluation (MORE) trial.

VTEs — Safety considerations when screening women for therapy with EVISTA

• Women with active or past history of VTEs should NOT be prescribed EVISTA
• In clinical trials, women treated with EVISTA had an increased risk of VTEs. The greatest risk for DVT and PE occurs within the first 4 months
• Because immobilization increases the risk for VTEs, EVISTA should be discontinued at least 72 hours prior to and during prolonged immobilization. Therapy with EVISTA should be resumed only after the patient is fully ambulatory. In addition, women should be advised to move around periodically during prolonged travel. The risk-benefit balance should be considered in women at risk for thromboembolic disease for other reasons, such as CHF, superficial thrombophlebitis, and active malignancy

Increased risk of DVT and PE has been reported with EVISTA use. EVISTA is contraindicated in women with active or past history of VTE, including DVT, PE, and retinal vein thrombosis.

1. Curr Med Res Opin. 2005;21:1441-1452.
2. J Natl Cancer Inst. 2004;96:1751-1761.
3. JAMA. 2006;295:2727-2741.
4. Breast Cancer Res Treat. 2001;65:125-134.
5. N Engl J Med. 2006;355:125-137.
6. Data on file, Eli Lilly and Company (EVI20090109).
7. Arch Intern Med. 1998;158:585-593.
8. JAMA. 1999;282:637-645.
9. J Clin Endocrinol Metab. 2002;87:3609-3617.

Important Safety Information for EVISTA

Contraindications

• EVISTA is contraindicated in nursing women and in women who are or may become pregnant, as it may cause fetal harm. EVISTA is also contraindicated in women with active or past venous thromboembolic events (VTEs), including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis.

Warnings and Precautions

• In a study of postmenopausal women at high risk for cardiovascular disease taking EVISTA, there was no increase in the incidence of stroke; however, there was an increase in death due to stroke. EVISTA also did not increase or decrease the incidence of overall mortality, cardiovascular mortality, or heart attack. The risk-benefit balance should be considered in women at risk for stroke, such as those with prior stroke or transient ischemic attack (TIA), atrial fibrillation, hypertension, or cigarette smoking.
• EVISTA should be used with caution in patients with hepatic impairment or moderate/severe renal impairment since safety and efficacy have not been established in these patients.
• The safety of concomitant use of EVISTA with systemic estrogens has not been established and its use is not recommended.

Adverse Reactions

• The common adverse reactions considered to be drug related:

• Adverse reactions occurring in the clinical trials at a frequency ≥2.0% in either group and in more EVISTA-treated women than in placebo-treated women include:

• The majority of adverse reactions occurring during the osteoporosis prevention and treatment studies were mild and generally did not require discontinuation of therapy.

For additional information, please see the full Prescribing Information and Medication Guide.

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EVISTA is a once-daily 60-mg tablet. Supplemental calcium and/or vitamin D should be added to diet if daily intake is inadequate.

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