Version May 2024
Increased risk of deep vein thrombosis and pulmonary embolism have been reported with raloxifene. Women with active or past history of VTE should not take raloxifene.
Increased risk of death due to stroke occurred in a trial in postmenopausal women with documented coronary heart disease or increased risk for major coronary events. Consider the risk-benefit balance in women at risk for stroke.
Osteoporosis, postmenopausal, fracture risk reduction (alternative agent):
Note: May be used to reduce the risk of vertebral fracture in patients in whom first-line therapies are not appropriate, or in patients who are also at increased risk of invasive breast cancer; use has not been associated with reduction in hip or nonvertebral fractures (Ref). Prior to use, evaluate and treat any potential causes of secondary osteoporosis (eg, severe vitamin D deficiency) (Ref). Ensure adequate calcium and vitamin D intake during therapy.
Oral: 60 mg once daily.
Discontinuation of therapy: If continued osteoporosis therapy is necessary after discontinuation, switch to antiresorptive therapy (eg, with a bisphosphonate) (Ref).
Risk reduction for invasive breast cancer in postmenopausal females: Oral: 60 mg once daily.
Duration of therapy for breast cancer risk reduction: 5 years; may be used longer than 5 years in females with osteoporosis where breast cancer risk reduction is a secondary benefit (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≤50 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Peripheral edema (3% to 14%)
Endocrine & metabolic: Hot flash (8% to 29%)
Infection: Infection (11%)
Neuromuscular & skeletal: Arthralgia (11% to 16%), leg cramps (≤12%), muscle spasm (≤12%)
Respiratory: Flu-like symptoms (14% to 15%)
1% to 10%:
Cardiovascular: Chest pain (3%), syncope (<2%), venous thromboembolism (1% to 2%; includes deep vein thrombosis, pulmonary embolism, retinal vein thrombosis)
Central nervous system: Insomnia (6%), hypoesthesia (<2%), neuralgia (<2%)
Dermatologic: Skin rash (6%), diaphoresis (3%)
Endocrine & metabolic: Weight gain (9%)
Gastrointestinal: Abdominal pain (7%), vomiting (5%), gastrointestinal disease (3%), flatulence (2% to 3%), gastroenteritis (≤3%)
Genitourinary: Vaginal hemorrhage (3% to 6%), mastalgia (4%), leukorrhea (3%), urinary tract abnormality (3%), uterine disease (3%), endometrium disease (≤3%)
Neuromuscular & skeletal: Myalgia (8%), tendinopathy (4%)
Respiratory: Bronchitis (10%), sinusitis (10%), pharyngitis (8%), pneumonia (3%), laryngitis (≤2%)
<1%, postmarketing, and/or case reports: Cerebrovascular accident, decreased LDL cholesterol (Delmas 1997; Walsh 1998), decreased serum cholesterol (Delmas 1997; Walsh 1998), decreased serum fibrinogen (Walsh 1998), hypertriglyceridemia (in women with a history of increased triglycerides in response to oral estrogens), retinal vein occlusion, superficial thrombophlebitis
History of or current venous thromboembolic disorders (including DVT, PE, and retinal vein thrombosis); pregnancy.
Canadian labeling (additional contraindications not in US labeling): Hypersensitivity to raloxifene or any component of the formulation; patients of childbearing potential.
Concerns related to adverse effects:
• Thromboembolic events: [US Boxed Warning]: Raloxifene may increase the risk for deep vein thrombosis (DVT) and pulmonary embolism (PE); use is contraindicated in patients with history of or current venous thromboembolic disorders (including DVT, PE, or retinal vein thrombosis). Consider risks versus benefits in females at risk for thromboembolism (heart failure [HF], superficial thrombophlebitis, active malignancy). The risk for DVT and PE are higher during the first 4 months of treatment. Superficial thrombophlebitis has also been reported.
Disease-related concerns:
• Breast cancer history: The use of raloxifene has not been adequately studied in females with a prior history of breast cancer.
• Cardiovascular disease: [US Boxed Warning]: The risk of death due to stroke is increased in postmenopausal females with coronary heart disease or at increased risk for major coronary events; consider risks versus benefits in females at risk for stroke. Do not use for primary or secondary prevention of cardiovascular disease. Assess risks versus benefits in females at risk for stroke (eg, prior stroke, transient ischemic attack, atrial fibrillation, hypertension, smokers).
• Hepatic impairment: Use with caution in patients with hepatic impairment; safety and efficacy have not been established.
• Hypertriglyceridemia: Females with a history of marked elevated triglycerides (>5.6 mmol/L or >500 mg/dL) in response to treatment with oral estrogens (or estrogen/progestin) may also develop elevated triglycerides when treated with raloxifene; monitor triglycerides.
• Renal impairment: Use with caution in patients with moderate to severe renal impairment; safety and efficacy have not been established.
• Uterine bleeding: Investigate unexplained uterine bleeding.
Concurrent drug therapy issues:
• Estrogens: Concurrent use with systemic estrogen therapy is not recommended; safety has not been established.
Special populations:
• Males: Safety and efficacy have not been established in men. Raloxifene is not indicated for use in men.
• Premenopausal females: Safety has not been established in premenopausal females; use is not indicated and not recommended.
Other warnings/precautions:
• Appropriate use: Raloxifene does not eliminate the risk of breast cancer; investigate unexplained breast abnormality that occurs during treatment. Raloxifene is not indicated for treatment of invasive breast cancer, to reduce the risk of recurrence of invasive breast cancer, or to reduce the risk of noninvasive breast cancer. The efficacy (for breast cancer risk reduction) in females with inherited BRCA1 and BRCA1 mutations has not been established.
• Prolonged immobilization: Discontinue raloxifene at least 72 hours prior to and during prolonged immobilization (postoperative recovery or prolonged bed rest); restart only once patient fully ambulatory. Advise patients to move periodically during prolonged travel.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Evista: 60 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Generic: 60 mg
Yes
Tablets (Evista Oral)
60 mg (per each): $7.92
Tablets (Raloxifene HCl Oral)
60 mg (per each): $0.53 - $8.01
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Evista: 60 mg [contains fd&c blue #2 (indigo carm) aluminum lake, polysorbate 80]
Generic: 60 mg
May be administered at any time of day without regard to meals.
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088593.pdf, must be dispensed with this medication.
Osteoporosis, postmenopausal, fracture risk reduction: Treatment and prevention of postmenopausal osteoporosis.
Risk reduction for invasive breast cancer: Risk reduction of invasive breast cancer in postmenopausal females with osteoporosis; risk reduction of invasive breast cancer in postmenopausal females with high risk for invasive breast cancer (high risk is defined as at least 1 breast biopsy showing lobular carcinoma in situ or atypical hyperplasia, one or more first-degree relatives with breast cancer, or a 5-year predicted risk of breast cancer 1.66% or more [based on the modified Gail model]; factors included in the modified Gail model include current age, number of first-degree relatives with breast cancer, number of breast biopsies, age at menarche, nulliparity, or age of first live birth).
Limitations of use: Raloxifene does not eliminate the risk of breast cancer; patients should have a breast exam and mammogram prior to initiating raloxifene and continue regular breast exams and mammograms as per current guideline recommendations. Raloxifene is not indicated for the treatment of invasive breast cancer or reduction of the risk of recurrence. Raloxifene is not indicated for the reduction of the risk of noninvasive breast cancer. There are no data available regarding the effect of raloxifene on invasive breast cancer incidence in females with inherited mutations BRCA1, BRCA2 to be able to make specific recommendations on the effectiveness of raloxifene.
Evista may be confused with Eovist
Raloxifene may be confused with ospemifene, toremifene
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Evista brand name for raloxifene [US, Canada, and multiple international markets] may be confused with Avinza brand name for morphine [Puerto Rico] and Invanz brand name for ertapenem [US, Canada, Qatar]
Substrate of P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Bile Acid Sequestrants: May decrease the absorption of Raloxifene. Management: Consider separating the doses of raloxifene and bile acid sequestrants by at least 4 hours. Risk D: Consider therapy modification
Estrogen Derivatives: May enhance the adverse/toxic effect of Raloxifene. Risk X: Avoid combination
Fluoroestradiol F18: Selective Estrogen Receptor Modulators may diminish the diagnostic effect of Fluoroestradiol F18. Management: Image patients with fluoroestradiol F-18 prior to starting systemic endocrine therapies that block the estrogen receptor. Use of fluoroestradiol F-18 should not delay indicated treatment. Risk D: Consider therapy modification
Levothyroxine: Raloxifene may decrease the absorption of Levothyroxine. Management: Consider separating doses of raloxifene and levothyroxine by several hours. Monitor for reduced effects of levothyroxine and reduced serum concentrations of thyroxine if raloxifene and levothyroxine are used concomitantly. Risk D: Consider therapy modification
Ospemifene: Selective Estrogen Receptor Modulators may enhance the adverse/toxic effect of Ospemifene. Ospemifene may also enhance adverse/toxic effects of other Selective Estrogen Receptor Modulators. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Raloxifene may diminish the anticoagulant effect of Vitamin K Antagonists. Raloxifene may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Raloxifene is not indicated for use in females of reproductive potential.
Raloxifene is contraindicated during pregnancy.
It is not known if raloxifene is present in breast milk.
Raloxifene is not indicated for use in females of reproductive potential.
Osteoporosis prevention or treatment: Ensure adequate calcium and vitamin D intake; if dietary intake is inadequate, dietary supplementation is recommended. Females and males should consume:
Calcium: 1,000 mg/day (males: 50 to 70 years of age) or 1,200 mg/day (females ≥51 years of age and males ≥71 years of age) (IOM 2011; NOF [Cosman 2014]).
Vitamin D: 800 to 1,000 units daily (age ≥50 years) (NOF [Cosman 2014]). Recommended dietary allowance (RDA): 600 units daily (age ≤70 years) or 800 units daily (age ≥71 years) (IOM 2011).
Lipid profile (in females at risk for hypertriglyceridemia); mammogram and breast exam (prior to and regularly during treatment).
Osteoporosis: Serial bone mineral density (BMD) should be evaluated at baseline and every 1 to 3 years (usually at ~2 years following initiation of therapy, then more or less frequently depending on patient-specific factors and stability of BMD) (AACE/ACE [Camacho 2020]; ES [Eastell 2019]; NOF [Cosman 2014]); annual measurements of height and weight, assessment of chronic back pain; serum calcium and 25(OH)D; may consider monitoring biochemical markers of bone turnover (eg, fasting serum CTX or urinary NTX) at baseline, 3 months, and 6 months, to assess treatment response and adherence to therapy (ES [Eastell 2019]).
Raloxifene is an estrogen agonist/antagonist (a selective estrogen receptor modulator [SERM]); selective binding activates estrogenic pathways in some tissues and antagonizes estrogenic pathways in other tissues. Raloxifene acts like an estrogen agonist in the bone to prevent bone loss and has estrogen antagonist activity to block some estrogen effects in the breast and uterine tissues. Raloxifene decreases bone resorption, increasing bone mineral density and decreasing fracture incidence.
Absorption: Rapid; ~60%
Distribution: 2,348 L/kg
Protein binding: Highly protein bound (95% to albumin and α-glycoprotein); does not bind to sex-hormone-binding globulin
Metabolism: Hepatic, extensive first-pass metabolism; metabolized to glucuronide conjugates
Bioavailability: ~2%
Half-life elimination: 27.7 hours (following a single dose); 32.5 hours (following multiple doses)
Excretion: Feces (primarily); urine (<0.2% as unchanged drug; <6% as glucuronide conjugates)
Altered kidney function: Raloxifene AUC was 122% higher in patients with moderate to severe renal impairment.
Hepatic function impairment: Raloxifene apparent clearance was reduced 56% and plasma concentrations were increased 150% in patients with mild hepatic impairment.
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