Raloxifene

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.

• Raloxifene hydrochloride is an estrogen agonist/antagonist indicated for: Treatment and prevention of osteoporosis in postmenopausal women. ( 1.1 ) Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis.ICD-10: C50.919, M81.0

• Active or past history of venous thromboembolism, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. (4.1) Pregnancy (4.2 , 8.1) 4.1 Venous Thromboembolism Raloxifene hydrochloride tablets are 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) ] .contraindicated

60 mg tablet orally once daily. (2.1) 2.1 Recommended Dosing The recommended dosage is one 60 mg raloxifene hydrochloride tablet 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.

Venous Thromboembolism : Increased risk of deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. Discontinue use 72 hours prior to and during prolonged immobilization. (5.1 , 6.1) Death Due to Stroke : 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. No increased risk of stroke was seen in this trial. Consider risk-benefit balance in women at risk for stroke. (5.2 , 14.5) Cardiovascular Disease : Raloxifene hydrochloride should not be used for the primary or secondary prevention of cardiovascular disease. (5.3, 14.5) Premenopausal Women : Use is not recommended. (5.4) Hepatic Impairment : Use with caution. (5.5) Concomitant Use with Systemic Estrogens : Not recommended. (5.6) Hypertriglyceridemia : If previous treatment with estrogen resulted in hypertriglyceridemia, monitor serum triglycerides. (5.7) 5.1 Venous Thromboembolism In clinical trials, raloxifene hydrochloride-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 hydrochloride 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.

Adverse reactions (>2% and more common than with placebo) include: hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, sweating. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 hydrochloride in 8429 patients who were enrolled in placebo-controlled trials, including 6666 exposed for 1 year and 5685 for at least 3 years. Osteoporosis Treatment Clinical Trial (MORE) — The safety of raloxifene in the treatment of osteoporosis was assessed in a large (7705 patients) multinational, placebo-controlled trial. Duration of treatment was 36 months, and 5129 postmenopausal women were exposed to raloxifene hydrochloride (2557 received 60 mg/day, and 2572 received 120 mg/day). The incidence of all-cause mortality was similar among groups: 23 (0.9%) placebo, 13 (0.5%) raloxifene hydrochloride-treated (raloxifene hydrochloride 60 mg), and 28 (1.1%) raloxifene hydrochloride 120 mg women died. Therapy was discontinued due to an adverse reaction in 10.9% of raloxifene hydrochloride-treated women and 8.8% of placebo-treated women.

Pediatric Use : Safety and effectiveness not established. (8.4) 8.1 Pregnancy Risk Summary Raloxifene hydrochloride is contraindicated for use in pregnant women, and is not indicated for use in females of reproductive potential. Based on mechanism of action, raloxifene hydrochloride may block the important functions that estrogen has during all stages of pregnancy [see Clinical Pharmacology (12.1) ] . Limited data with raloxifene hydrochloride use in pregnant women are insufficient to inform any drug associated risks for births defects or miscarriage. In rabbits and rats dosed during organogenesis or during gestation and lactation, raloxifene hydrochloride produced multiple adverse reproductive and developmental effects, including abortion; fetal anomalies; and delayed or disrupted parturition leading to maternal and neonatal mortality, at doses less than or similar to the maximum recommended human dose (based on human body surface area comparison). Data Animal Data In the developmental and reproductive toxicity studies conducted with raloxifene hydrochloride, numerous adverse effects were observed in multiple animal species. In rabbits dosed during organogenesis, abortion and a low rate of fetal heart anomalies (ventricular septal defects) occurred at doses ≥0.1 mg/kg (≥0.04 times the human dose based on surface area, mg/m 2 ).

Metabolism

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.

In an 8-week study of 63 postmenopausal women, a dose of raloxifene hydrochloride 600 mg/day was safely tolerated. In clinical trials, no raloxifene overdose has been reported. In postmarketing spontaneous reports, raloxifene overdose has been reported very rarely (less than 1 out of 10,000 [<0.01%] patients treated). The highest overdose has been approximately 1.5 grams. No fatalities associated with raloxifene overdose have been reported. Adverse reactions were reported in approximately half of the adults who took ≥180 mg raloxifene hydrochloride and included leg cramps and dizziness. Two 18-month-old children each ingested raloxifene hydrochloride 180 mg. In these two children, symptoms reported included ataxia, dizziness, vomiting, rash, diarrhea, tremor, and flushing, as well as elevation in alkaline phosphatase. There is no specific antidote for raloxifene. No mortality was seen after a single oral dose in rats or mice at 5000 mg/kg (810 times the human dose for rats and 405 times the human dose for mice based on surface area, mg/m 2 ) or in monkeys at 1000 mg/kg (80 times the AUC in humans).

• Dec 9, 1997NDANDA020815Lilly
• Mar 4, 2014ANDAANDA078193Teva Pharms Usa
• Sep 24, 2014ANDAANDA090842Invagen Pharms
• Aug 28, 2015ANDAANDA204310Aurobindo Pharma
• Mar 22, 2016ANDAANDA204491Glenmark Pharms Ltd
• Apr 8, 2016ANDAANDA208206Amneal Pharms
• Oct 12, 2016ANDAANDA206384Sciegen Pharms
• Aug 18, 2020ANDAANDA211324Cadila Pharms Ltd

1. 1Nausea8445.3%
2. 2Fall8305.2%
3. 3Drug Ineffective8245.2%
4. 4Pain In Extremity7654.8%
5. 5Pain7374.6%
6. 6Arthralgia7024.4%
7. 7Dizziness6724.2%
8. 8Fatigue6624.1%
9. 9Muscle Spasms6163.9%
10. 10Headache6153.9%
11. 11Diarrhoea5493.4%
12. 12Body Height Decreased5343.3%
13. 13Back Pain5093.2%
14. 14Dyspnoea5053.2%
15. 15Asthenia4883.1%

Recent PubMed references pinned to Raloxifene as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Raloxifene Beyond Osteoporosis: Unlocking Neurorestoration Through Remyelination, Inflammatory Regulation, and Neuroimmune Modulation in CNS Pathologies.
  International immunopharmacology · 2026 · Banerjee C, Singh RK, Mehan S, et al.
  PMID 42055490DOI 10.1016/j.intimp.2026.116668
• Estradiol and Raloxifene Protect Ovariectomized Mice from Acute Kidney Injury via G Protein-Coupled Estrogen Receptor-Mediated Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Activation.
  International journal of molecular sciences · 2026 · Wang Y, Song Y, Dai J, et al.
  PMID 41977254DOI 10.3390/ijms27073070
• Genomic and AI-driven discovery in chronic prostatitis: Causal role of ITPR3 and therapeutic repurposing of raloxifene.
  European journal of pharmacology · 2026 · Li Y, Dong X, Sun R, et al.
  PMID 41581718DOI 10.1016/j.ejphar.2026.178598
• Effects of estradiol, tamoxifen, and raloxifene on human temporal lobe cortex astroglial cell spreading.
  Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology · 2026 · Silva I, Naftolin FN, Oliveira Santana V, et al.
  PMID 41568550DOI 10.1080/09513590.2026.2618881
• Effects of Combined Treatment With Selective Androgen and Estrogen Receptor Modulators Ostarine and Raloxifen on Bone Tissue In Ovariectomized Rats.
  Calcified tissue international · 2025 · Hoffmann DB, Staub M, Böker KO, et al.
  PMID 41134342DOI 10.1007/s00223-025-01431-4
• Rational design, synthesis, and biological evaluation of Raloxifene-based potent degrader of estrogen receptor alpha.
  Bioorganic chemistry · 2025 · Tian Y, Sun Y, Han K, et al.
  PMID 41124803DOI 10.1016/j.bioorg.2025.109063
• Intelligence modeling of solubility of raloxifene and density of solvent for green supercritical processing of medicines for enhanced solubility.
  Scientific reports · 2025 · Alsaab HO, Althobaiti YS
  PMID 41044345DOI 10.1038/s41598-025-18223-3
• Solubility enhancement of raloxifene hydrochloride by in situ micronization technique: physicochemical characterization and pharmacokinetic studies.
  Drug development and industrial pharmacy · 2025 · Dayani L, Varshosaz J, Emami Bafrani J, et al.
  PMID 41017460DOI 10.1080/03639045.2025.2566748

The 10 most recently updated of 86 ClinicalTrials.gov registrations naming Raloxifene as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Bioequivalence ANDA SNP Clinical Study - Raloxifene and Single Nucleotide Polymorphisms
  Active not recruiting · Phase 2 · Phase 3 · Interventional · 600 enrolled · Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair
  NCT06062810updated 2026-04-23
• New Treatment Strategies and Epigenetic Biomarker for Management of Benign Prostatic Hyperplasia
  Recruiting · Phase 2 · Interventional · 242 enrolled · Beth Israel Deaconess Medical Center
  NCT06944145updated 2026-03-23
• Memantine +/- Raloxifene for Cognitive Preservation After Radiation Therapy to the Brain
  Not yet recruiting · Phase 2 · Interventional · 108 enrolled · The University of Texas Health Science Center at San Antonio
  NCT07470606updated 2026-03-13
• A Prospective, Safety, and Efficacy Clinical Trial of Pressurized Intraperitoneal Aerosol Therapy for Peritoneal Metastasis of Colorectal Cancer
  Recruiting · Phase 1 · Interventional · 42 enrolled · Second Affiliated Hospital, School of Medicine, Zhejiang University
  NCT07349043updated 2026-01-16
• XCHT for Irinotecan-Induced Gut Toxicities (Randomized Controlled Trial)
  Recruiting · Interventional · 98 enrolled · Guangzhou University of Traditional Chinese Medicine
  NCT06055179updated 2025-07-01
• Johns Hopkins Breast Cancer Program Hormone Therapy Longitudinal Database
  Completed · Observational · 329 enrolled · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  NCT01937052updated 2024-12-13
• Induction of Ovulation With Raloxifene or Clomiphene Citrate in Polycystic Ovarian Syndrome
  Completed · Phase 3 · Interventional · 82 enrolled · Hospital de Clinicas de Porto Alegre
  NCT00427700updated 2024-08-21
• Comparison of Tibolone and Raloxifene on Bone Mineral Density in Osteopenic Postmenopausal Women (P06090)
  Completed · Phase 4 · Interventional · 324 enrolled · Organon and Co
  NCT00431431updated 2024-08-15
• A Comparison Study With Alendronate and Raloxifene in Postmenopausal Women With Osteoporosis (0217-189)
  Completed · Phase 3 · Interventional · 400 enrolled · Organon and Co
  NCT00389740updated 2024-08-14
• XCHT for Irinotecan-Induced Gut Toxicities (Run-in Study)
  Completed · Interventional · 24 enrolled · Guangzhou University of Traditional Chinese Medicine
  NCT04926545updated 2024-07-30

CPIC-curated drug–gene pairs for Raloxifene. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• FDPSCPIC D (provisional)

Frequently asked questions

How does Raloxifene work?

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.

What is Raloxifene used for?

According to FDA labeling, Raloxifene carries indications including: Raloxifene hydrochloride is an estrogen agonist/antagonist indicated for: Treatment and prevention of osteoporosis in postmenopausal women. ( 1.1 ) Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Raloxifene?

Raloxifene is classified as Selective estrogen receptor modulators, Estrogen Agonist/Antagonist, Selective Estrogen Receptor Modulators, Bone Resorption Inhibition, Cholesterol Metabolism Alteration.

What are the brand names for Raloxifene?

Raloxifene is marketed under brand names including Evista.

What are the contraindications for Raloxifene?

Raloxifene labeling lists contraindications including: Active or past history of venous thromboembolism, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. (4.1) Pregnancy (4.2 , 8.1) 4.1 Venous Thromboembolism Raloxifene hydrochloride tablets are 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) ] .. Always consult the full prescribing information and a clinician.