Class: Estrogen Agonists-Antagonists
ATC Class: G03XC01
VA Class: HS900
Chemical Name: 6-Hydroxy-2-(p-hydroxyphenyl)benzo[b]thien-3-yl-p-(2-piperidinoethoxy)phenyl ketone hydrochloride
Molecular Formula: C28H27NO4S•ClH
CAS Number: 82640-04-8
Medically reviewed on Mar 26, 2018
Uses for Raloxifene Hydrochloride
Osteoporosis in Postmenopausal Women
Prevention of osteoporosis in postmenopausal women.1 2 3 4 5 6 7 16 17 23 55 69 108 Risk factors for postmenopausal osteoporosis and related fractures include early menopause, advanced age, low bone mineral density (BMD), low body mass index (BMI), previous fracture or family history of fracture/osteoporosis, excessive alcohol intake, smoking, inadequate physical activity, low calcium and vitamin D intake, certain drugs (e.g., glucocorticoids), and medical conditions or diseases (e.g., rheumatoid arthritis, diabetes mellitus, Cushing syndrome, hyperparathyroidism).105 106
In addition to adequate intake of calcium/vitamin D and other lifestyle modifications (e.g., exercise, avoidance of excessive alcohol and tobacco use), experts recommend that pharmacologic therapy for osteoporosis be considered in postmenopausal women with high risk of fractures (generally those who have experienced a previous hip or vertebral fracture or who have low BMD); pharmacologic therapy also may be considered in postmenopausal women with low bone mass, although there is less evidence supporting overall fracture risk reduction in such patients.105 106
Use of a drug with proven antifracture efficacy is recommended; experts generally recommend raloxifene as a second- or third-line agent after other therapies (e.g., bisphosphonates) have been attempted.105 106
American College of Rheumatology (ACR) recommends optimizing calcium and vitamin D intake and lifestyle modifications (e.g., diet, smoking cessation, weight-bearing or resistance-training exercise) in all patients receiving long-term glucocorticoid therapy; in addition, pharmacologic therapy with an oral bisphosphonate is recommended in patients at moderate-to-high risk of fracture.622 Oral bisphosphonates are preferred because of their demonstrated antifracture benefits, safety, and cost; experts state raloxifene may be used in postmenopausal women if no other therapy is available.622
Reduction in the incidence of invasive breast cancer in postmenopausal women at high risk for developing the disease.1 109 113 117 118 Effect comparable to that of tamoxifen in reducing the risk of invasive breast cancer (STAR trial).1 109 113 120 Effect on breast cancer incidence in women with BRCA1 or BRCA2 genetic mutations not established.1
Not studied in women with a history of exposure to thoracic radiation, which is considered a possible risk factor for breast cancer.118
Raloxifene Hydrochloride Dosage and Administration
Available as raloxifene hydrochloride; dosage expressed in terms of the salt.1
Prevention in Postmenopausal WomenOral
Treatment in Postmenopausal WomenOral
Reduction in the Incidence of Invasive Breast CancerOral
60 mg daily.1 Optimum duration of therapy unknown.1 ASCO recommends a treatment duration of 5 years.117 If a patient is receiving raloxifene as treatment for osteoporosis, for which breast cancer reduction is a secondary goal, ASCO suggests that treatment duration may be extended beyond 5 years.117
Cautions for Raloxifene Hydrochloride
Women who are or may become pregnant.1
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
Fetal/Neonatal Morbidity and Mortality
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.)
Use in Premenopausal Women
Effects on Lipids
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
Effects on the Breast
Not studied in women with a history of breast cancer.1
Use in Men
Safety and efficacy not evaluated.1
Category X.1 (See Fetal/Neonatal Morbidity and Mortality and also Contraindications under Cautions.)
Not known whether raloxifene is distributed into milk.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
Interactions for Raloxifene Hydrochloride
Metabolism apparently not mediated by CYP isoenzymes.1
Concomitant administration with other highly protein-bound drugs not expected to affect plasma raloxifene concentrations.1 Caution advised if used concomitantly with other highly protein-bound drugs.1
Amoxicillin and ampicillin
Ampicillin: Decreased peak plasma raloxifene concentrations; no change in systemic exposure to raloxifene1
Amoxicillin: No change in raloxifene concentrations1
Can be administered concomitantly1
Anion-exchange resins (cholestyramine)
Decreased absorption and enterohepatic cycling of raloxifene with concomitant cholestyramine administration; similar interaction expected with other anion-exchange resins1
Antacids (aluminum- and magnesium-containing, calcium carbonate)
No change in systemic exposure of raloxifene1
Can be administered concomitantly1
Decreased warfarin effects; no effect on warfarin pharmacokinetics observed1
Monitor PT carefully1
Concomitant use not specifically studied1
Potential for altered protein binding of diazepam1
Potential for altered protein binding of diazoxide1
No change in digoxin pharmacokinetics1
Can be administered concomitantly1
Concomitant use not recommended1
No substantial change in plasma raloxifene concentrations1
Potential for altered protein binding of lidocaine1
No change in methylprednisolone pharmacokinetics1
Can be administered concomitantly with corticosteroids1
No change in protein binding of phenytoin1
Raloxifene Hydrochloride Pharmacokinetics
High-fat meal increases peak plasma concentration and extent of absorption of raloxifene, but does not substantially affect systemic exposure.1
Plasma raloxifene concentrations are 150% higher in patients with cirrhosis (Child-Pugh class A) and total serum bilirubin concentrations of 0.6–2 mg/dL than in individuals with normal hepatic function.1 Pharmacokinetics not studied in individuals with moderate or severe hepatic impairment.1
Plasma raloxifene concentrations in those with mild renal impairment are similar to values in women with normal renal function.1 96 AUC of raloxifene is 122% higher in individuals with moderate renal impairment (Clcr 31–50 mL/minute) or severe renal impairment (Clcr ≤30 mL/minute) than in individuals with normal renal function.1
Plasma Protein Binding
Undergoes extensive first-pass metabolism to glucuronide conjugates.1 27 33 34 35 36 55 Does not appear to be metabolized by CYP isoenzymes.1 Conjugates converted back to the parent drug in various tissues.1 27
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
Advice to Patients
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.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Raloxifene Hydrochloride Tablets
AHFS DI Essentials. © Copyright 2018, Selected Revisions March 26, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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