Raloxifene Hydrochloride

Estrogen agonist-antagonist; a nonsteroidal benzothiophene derivative.1 2 3 13 14 15 16 17 55 69 70

Osteoporosis

Prevention of osteoporosis in postmenopausal women.1 2 3 4 5 6 7 16 17 23 55 69 108

Treatment of osteoporosis in postmenopausal women.1 53 69 98 99 108

Use supplemental calcium and/or vitamin D concomitantly if daily dietary intake is considered inadequate.1 2 3 4 5 6 7 16 17 23 55 69 108

Corticosteroid-induced Osteoporosis

May prevent or treat corticosteroid-induced bone loss†.107 American College of Rheumatology states that raloxifene can be offered to selected postmenopausal corticosteroid-treated women who refuse hormone replacement therapy or other antiresorptive agents (e.g., bisphosphonates, calcitonin) or in whom such therapies are contraindicated.107

Breast Cancer

Reduction in the incidence of invasive breast cancer in postmenopausal women with osteoporosis.1 93 100

Reduction in the incidence of invasive breast cancer in postmenopausal women at high risk for developing the disease.1 109 113 Effect comparable to that of tamoxifen in reducing the risk of invasive breast cancer (STAR trial).1 109 113 No effect on the risk of lobular carcinoma in situ or ductal carcinoma in situ (STAR trial).113 Effect on breast cancer incidence in women with BRCA1 or BRCA2 genetic mutations not established.1

Not indicated for the treatment of breast cancer or to reduce the risk of recurrence of breast cancer.1 Not indicated for reduction in the risk of noninvasive breast cancer.1

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

• 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

• Importance of providing patient a copy of manufacturer’s patient information.1

• Risk of venous thromboembolic events.1 Notify clinician if signs or symptoms of thromboembolic disorder occur.52 Avoid prolonged restrictions in movement while traveling.1 52 Discontinue raloxifene ≥72 hours before and during prolonged immobilization (e.g., postsurgery recovery, prolonged bed rest).1

• Potential for increased incidence of hot flushes (flashes); drug is not effective in reducing hot flushes associated with estrogen deficiency.1

• When used for osteoporosis, importance of taking supplemental calcium and/or vitamin D if daily dietary intake is inadequate.1 Importance of weight-bearing exercise and modification of other risk factors for osteoporosis (e.g., smoking, alcohol intake) if needed.1

• When used to reduce the incidence of invasive breast cancer, advise patient regarding benefits and risks of therapy as well as appropriate indications.1 Need for regular breast examinations and mammograms.1

• Importance for women who are or may become pregnant or who are lactating to avoid taking the drug.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)