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 (14.1, 14.2)].

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 (14.3)].

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 (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. 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.

2.1 Recommended Dosing

The recommended dosage is one raloxifene hydrochloride tablets, USP 60 mg 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 to 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.

4.1 Venous Thromboembolism

Raloxifene hydrochloride tablets, USP 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, Women Who May Become Pregnant, and Nursing Mothers

Raloxifene hydrochloride tablets, USP is contraindicated in pregnancy, in women who may become pregnant, and in nursing mothers [see Use in Specific Populations (8.1, 8.3)].

Raloxifene hydrochloride tablets, USP may cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

In rabbit studies, abortion and a low rate of fetal heart anomalies (ventricular septal defects) occurred in rabbits at doses ≥0.1 mg/kg (≥0.04 times the human dose based on surface area, mg/m2), and hydrocephaly was observed in fetuses at doses ≥10 mg/kg (≥4 times the human dose based on surface area, mg/m2). In rat studies, retardation of fetal development and developmental abnormalities (wavy ribs, kidney cavitation) occurred at doses ≥1 mg/kg (≥0.2 times the human dose based on surface area, mg/m2). Treatment of rats at doses of 0.1 to 10 mg/kg (0.02 to 1.6 times the human dose based on surface area, mg/m2) during gestation and lactation 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, raloxifene disrupted parturition, which resulted in maternal and progeny death and morbidity. Effects in adult offspring (4 months of age) included uterine hypoplasia and reduced fertility; however, no ovarian or vaginal pathology was observed.

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 (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 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 (14.5)].

5.3 Cardiovascular Disease

Raloxifene 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 raloxifene. Safety of raloxifene in premenopausal women has not been established and its use is not recommended.

5.5 Hepatic Impairment

Raloxifene 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 raloxifene 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 raloxifene. Women with this medical history should have serum triglycerides monitored when taking raloxifene.

5.8 Renal Impairment

Raloxifene 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

Raloxifene 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 raloxifene in men. Raloxifene 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. Raloxifene-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 raloxifene therapy should be investigated. Raloxifene does not eliminate the risk of breast cancer [see Clinical Studies (14.4)].

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 raloxifene in 8429 patients who were enrolled in placebo-controlled trials, including 6666 exposed for 1 year and 5685 for at least 3 years.

6.2 Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported very rarely since market introduction include retinal vein occlusion, stroke, and death associated with venous thromboembolism (VTE).

7.1 Cholestyramine

Concomitant administration of cholestyramine with raloxifene is not recommended. Although not specifically studied, it is anticipated that other anion exchange resins would have a similar effect. Raloxifene should not be co-administered with other anion exchange resins [see Clinical Pharmacology (12.3)].

7.2 Warfarin

If raloxifene is given concomitantly with warfarin or other warfarin derivatives, prothrombin time should be monitored more closely when starting or stopping therapy with raloxifene [see Clinical Pharmacology (12.3)].

7.3 Other Highly Protein-Bound Drugs

Raloxifene should be used with caution with certain other highly protein-bound drugs such as diazepam, diazoxide, and lidocaine. Although not examined, raloxifene 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 raloxifene with systemic estrogens has not been established and its use is not recommended.

7.5 Other Concomitant Medications

Raloxifene can be concomitantly administered with ampicillin, amoxicillin, antacids, corticosteroids, and digoxin [see Clinical Pharmacology (12.3)].

The concomitant use of raloxifene and lipid-lowering agents has not been studied.

8.1 Pregnancy

Pregnancy Category X. Raloxifene should not be used in women who are or may become pregnant [see Contraindications (4.2)].

8.3 Nursing Mothers

Raloxifene should not be used by lactating women [see Contraindications (4.2)]. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when raloxifene is administered to a nursing woman.

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 raloxifene, 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

Raloxifene 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

Raloxifene should be used with caution in patients with hepatic impairment [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)].

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 raloxifene lacks estrogen-like effects on the uterus and breast tissue.

12.2 Pharmacodynamics

Decreases in estrogen levels after oophorectomy or menopause lead to increases in bone resorption and accelerated bone loss. Bone is initially lost rapidly because the compensatory increase in bone formation is inadequate to offset resorptive losses. In addition to loss of estrogen, this imbalance between resorption and formation may be due to age-related impairment of osteoblasts or their precursors. In some women, these changes will eventually lead to decreased bone mass, osteoporosis, and increased risk for fractures, particularly of the spine, hip, and wrist. Vertebral fractures are the most common type of osteoporotic fracture in postmenopausal women.

In both the osteoporosis treatment and prevention trials, raloxifene resulted in consistent, statistically significant suppression of bone resorption and bone formation, as reflected by changes in serum and urine markers of bone turnover (e.g., bone-specific alkaline phosphatase, osteocalcin, and collagen breakdown products). The suppression of bone turnover markers was evident by 3 months and persisted throughout the 36-month and 24-month observation periods.

In a 31-week, open-label, radiocalcium kinetics study, 33 early postmenopausal women were randomized to treatment with once-daily raloxifene 60 mg, cyclic estrogen/progestin (0.625 mg conjugated estrogens daily with 5 mg medroxyprogesterone acetate daily for the first 2 weeks of each month [hormone therapy]), or no treatment. Treatment with either raloxifene or hormone therapy was associated with reduced bone resorption and a positive shift in calcium balance (-82 mg Ca/day and +60 mg Ca/day, respectively, for raloxifene and -162 mg Ca/day and +91 mg Ca/day, respectively, for hormone therapy). There were small decreases in serum total calcium, inorganic phosphate, total protein, and albumin, which were generally of lesser magnitude than decreases observed during estrogen or hormone therapy. Platelet count was also decreased slightly and was not different from estrogen therapy.

12.3 Pharmacokinetics

The disposition of raloxifene has been evaluated in more than 3000 postmenopausal women in selected raloxifene osteoporosis treatment and prevention clinical trials, using a population approach. Pharmacokinetic data also were obtained in conventional pharmacology studies in 292 postmenopausal women. Raloxifene exhibits high within-subject variability (approximately 30% coefficient of variation) of most pharmacokinetic parameters. Table 3 summarizes the pharmacokinetic parameters of raloxifene.

Absorption — Raloxifene is absorbed rapidly after oral administration. Approximately 60% of an oral dose is absorbed, but presystemic glucuronide conjugation is extensive. Absolute bioavailability of raloxifene is 2%. The time to reach average maximum plasma concentration and bioavailability are functions of systemic interconversion and enterohepatic cycling of raloxifene and its glucuronide metabolites. Administration of raloxifene HCl with a standardized, high-fat meal increases the absorption of raloxifene (Cmax 28% and AUC 16%), but does not lead to clinically meaningful changes in systemic exposure. Raloxifene can be administered without regard to meals.

Distribution — Following oral administration of single doses ranging from 30 to 150 mg of raloxifene HCl, the apparent volume of distribution is 2348 L/kg and is not dose dependent. Raloxifene and the monoglucuronide conjugates are highly (95%) bound to plasma proteins. Raloxifene binds to both albumin and α1-acid glycoprotein, but not to sex-steroid binding globulin.

Metabolism — Biotransformation and disposition of raloxifene in humans have been determined following oral administration of 14C-labeled raloxifene. Raloxifene undergoes extensive first-pass metabolism to the glucuronide conjugates: raloxifene-4′-glucuronide, raloxifene-6-glucuronide, and raloxifene-6,4′-diglucuronide. No other metabolites have been detected, providing strong evidence that raloxifene is not metabolized by cytochrome P450 pathways. Unconjugated raloxifene comprises less than 1% of the total radiolabeled material in plasma. The terminal log-linear portions of the plasma concentration curves for raloxifene and the glucuronides are generally parallel. This is consistent with interconversion of raloxifene and the glucuronide metabolites. Following intravenous administration, raloxifene is cleared at a rate approximating hepatic blood flow. Apparent oral clearance is 44.1 L/kg•hr. Raloxifene and its glucuronide conjugates are interconverted by reversible systemic metabolism and enterohepatic cycling, thereby prolonging its plasma elimination half-life to 27.7 hours after oral dosing. Results from single oral doses of raloxifene predict multiple-dose pharmacokinetics. Following chronic dosing, clearance ranges from 40 to 60 L/kg•hr. Increasing doses of raloxifene HCl (ranging from 30 to 150 mg) result in slightly less than a proportional increase in the area under the plasma time concentration curve (AUC).

Excretion — Raloxifene is primarily excreted in feces, and less than 0.2% is excreted unchanged in urine. Less than 6% of the raloxifene dose is eliminated in urine as glucuronide conjugates.

Special Populations

Pediatric — The pharmacokinetics of raloxifene has not been evaluated in a pediatric population [see Use in Specific Populations (8.4)].

Geriatric — No differences in raloxifene pharmacokinetics were detected with regard to age (range 42 to 84 years) [see Use in Specific Populations (8.5)].

Gender — Total extent of exposure and oral clearance, normalized for lean body weight, are not significantly different between age-matched female and male volunteers.

Race — Pharmacokinetic differences due to race have been studied in 1712 women, including 97.5% White, 1.0% Asian, 0.7% Hispanic, and 0.5% Black in the osteoporosis treatment trial and in 1053 women, including 93.5% White, 4.3% Hispanic, 1.2% Asian, and 0.5% Black in the osteoporosis prevention trials. There were no discernible differences in raloxifene plasma concentrations among these groups; however, the influence of race cannot be conclusively determined.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 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 raloxifene as a skeletal antiresorptive agent.

14.1 Treatment of Postmenopausal Osteoporosis

14.2 Prevention of Postmenopausal Osteoporosis

The effects of raloxifene 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. Raloxifene 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.

Table 6: Raloxifene (60 mg Once Daily) Related Increases in BMDa for the Three Osteoporosis Prevention Studies Expressed as Mean Percentage Increase vs . Placebob at 24 Monthsc

a Note: all BMD increases were significant (p≤0.001).
b All patients received calcium.
c Intent-to-treat analysis; last observation carried forward.
d Abbreviations: NA = North American, EU = European, INT = International.
e All women in the study had previously undergone hysterectomy.
	Study
Site	NAd %	EUd %	INTd, e %
Total Hip	2.0	2.4	1.3
Femoral Neck	2.1	2.5	1.6
Trochanter	2.2	2.7	1.3
Intertrochanter	2.3	2.4	1.3
Lumbar Spine	2.0	2.4	1.8

Raloxifene 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 raloxifene on forearm BMD were inconsistent between studies. In Study EU, raloxifene 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

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

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

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 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 was observed: 59 (1.2%) raloxifene-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 [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 (5.2, 5.3)].

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

Raloxifene hydrochloride tablets, USP 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

Raloxifene hydrochloride tablets, USP 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 raloxifene hydrochloride tablets, USP 60 mg 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 raloxifene hydrochloride tablets, USP is associated with the reduction of the risk of invasive breast cancer in postmenopausal women. Raloxifene hydrochloride tablets, USP 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 raloxifene hydrochloride tablets, USP treatment with the patient.

Raloxifene hydrochloride tablets, USP 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 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.