PRECAUTIONS

General Concurrent Estrogen Therapy —

The concurrent use of EVISTA and systemic estrogen or hormone replacement therapy (ERT or HRT) has not been studied in prospective clinical trials and therefore concomitant use of EVISTA with systemic estrogens is not recommended.

Lipid Metabolism —

EVISTA lowers serum total and LDL cholesterol by 6% to 11%, but does not affect serum concentrations of total HDL cholesterol or triglycerides. These effects should be taken into account in therapeutic decisions for patients who may require therapy for hyperlipidemia.

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.

Concurrent use of EVISTA and lipid-lowering agents has not been studied.

Endometrium —

EVISTA has not been associated with endometrial proliferation (see Clinical Studies and ADVERSE REACTIONS). Unexplained uterine bleeding should be investigated as clinically indicated.

Breast —

EVISTA has not been associated with breast enlargement, breast pain, or an increased risk of breast cancer (see Clinical Studies and ADVERSE REACTIONS). Any unexplained breast abnormality occurring during EVISTA therapy should be investigated.

History of Breast Cancer —

EVISTA has not been adequately studied in women with a prior history of breast cancer.

Use in Men —

Safety and efficacy have not been evaluated in men.

WARNINGS

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 could also occur. A less serious event, superficial thrombophlebitis, also has been reported more frequently with EVISTA.

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 replacement 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.