Raloxifene Hydrochloride

• Increased risk of deep vein thrombosis and pulmonary embolism have been reported with raloxifene
  [see Warnings and Precautions (
  
  
  

  5.1 Venous Thromboembolism

  In clinical trials, raloxifene-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 raloxifene 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, raloxifene should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest), and raloxifene therapy should be resumed only after the patient is fully ambulatory. In addition, women taking raloxifene 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 and Adverse Reactions ]

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  . Women with active or past history of venous thromboembolism should not take raloxifene
  [see Contraindications (
  
  
  

  4.1 Venous Thromboembolism

  Raloxifene 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 ]

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• 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
  
  
  

  [see Warnings and Precautions (
  
  
  

  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 raloxifene. During an average follow-up of 5.6 years, 59 (1.2%) raloxifene-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 to 2.24; p=0.0499). There was no statistically significant difference between treatment groups in the incidence of stroke (249 in raloxifene [4.9%] versus 224 placebo [4.4%]). Raloxifene 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 ]

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  ) and Clinical Studies (
  
  
  

  14.5 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 raloxifene hydrochloride 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 raloxifene hydrochloride was observed: 59 (1.2%) raloxifene hydrochloride-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 to 2.24; p=0.0499). The incidence of stroke did not differ significantly between treatment groups (249 with raloxifene hydrochloride [4.9%] versus 224 with placebo [4.4%]; hazard ratio 1.10; 95% confidence interval 0.92 to 1.32; p=0.30; 9.5 versus 8.6 per 1000 women-years)

  [see Warnings and Precautions ]

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Raloxifene hydrochloride tablets, USP is an estrogen agonist/antagonist indicated for:

• Treatment and prevention of osteoporosis in postmenopausal women. (
  
  
  
  1.1 Treatment and Prevention of Osteoporosis in Postmenopausal Women

  Raloxifene hydrochloride tablets, USP is indicated for the treatment and prevention of osteoporosis in postmenopausal women

  [see Clinical Studies ]

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• Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis. (
  
  
  
  1.2 Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis

  Raloxifene hydrochloride tablets, USP is indicated for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis

  [see Clinical Studies ]

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• Reduction in risk of invasive breast cancer in postmenopausal women at high risk for invasive breast cancer. (
  
  
  
  1.3 Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women at High Risk of Invasive Breast Cancer

  Raloxifene hydrochloride tablets, USP is indicated for the reduction in risk of invasive breast cancer in postmenopausal women at high risk of invasive breast cancer

  [see Clinical Studies ]

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  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 ]

  . 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. 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 raloxifene hydrochloride tablets, USP should be based upon an individual assessment of the benefits and risks.

  Raloxifene hydrochloride tablets, USP does not eliminate the risk of breast cancer. Patients should have breast exams and mammograms before starting raloxifene hydrochloride tablets, USP and should continue regular breast exams and mammograms in keeping with good medical practice after beginning treatment with raloxifene hydrochloride tablets, USP.

  Important Limitations of Use for Breast Cancer Risk Reduction

  • There are no data available regarding the effect of raloxifene on invasive breast cancer incidence in women with inherited mutations (BRCA1, BRCA2) to be able to make specific recommendations on the effectiveness of raloxifene hydrochloride tablets, USP.
  • Raloxifene hydrochloride tablets, USP is not indicated for the treatment of invasive breast cancer or reduction of the risk of recurrence.
  • Raloxifene hydrochloride tablets, USP is not indicated for the reduction in the risk of noninvasive breast cancer.
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Important Limitations: Raloxifene hydrochloride tablets, USP 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.

60 mg tablet orally once daily. (

60 mg, white to off-white, oval, biconvex, film coated tablets (not scored). They are debossed with ‘SG’ on one side and ‘306’ on other side.

• Pediatric Use: Safety and effectiveness not established. (
  
  
  
  8.4 Pediatric Use

  Safety and effectiveness in pediatric patients have not been established.
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