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 2019, Selected Revisions March 26, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
1. Eli Lilly and Company. Evista (raloxifene hydrochloride) tablets prescribing information. Indianapolis, IN; 2016 Dec.
2. Delmas PD, Bjarnason NH, Mitlak BH et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med. 1997; 337:1641-7. http://www.ncbi.nlm.nih.gov/pubmed/9385122?dopt=AbstractPlus
3. Boss SM, Huster WJ, Neild JA et al. Effects of raloxifene hydrochloride on the endometrium of postmenopausal women. Am J Obstet Gynecol. 1997; 177:1458-64. http://www.ncbi.nlm.nih.gov/pubmed/9423751?dopt=AbstractPlus
4. Gradishar WJ, Jordan VC. Clinical potential of new antiestrogens. J Clin Oncol. 1997; 15:840-52. http://www.ncbi.nlm.nih.gov/pubmed/9053512?dopt=AbstractPlus
5. Purdie DW. Selective oestrogen receptor modulation: HRT replacement therapy? Br J Obstet Gynaecol. 1997; 104:1103-5. (IDIS 394047)
6. El-Hajj Fuleihan G. Tissue-specific estrogens—the promise for the future. N Engl J Med. 1997; 337:1686-7. http://www.ncbi.nlm.nih.gov/pubmed/9385130?dopt=AbstractPlus
7. Compston JE. Designer oestrogens: fact or fantasy? Lancet. 1997; 350:676-7. (IDIS 390843)
8. Pennisi E. Drug’s link to genes reveals estrogen’s many sides. Science. 1996; 273:1171. http://www.ncbi.nlm.nih.gov/pubmed/8787121?dopt=AbstractPlus
9. Yang NN, Venugopalan M, Hardikar S et al. Identification of an estrogen response element activated by metabolites of 17β-estradiol and raloxifene. Science. 1996; 273:1222-5. http://www.ncbi.nlm.nih.gov/pubmed/8703055?dopt=AbstractPlus
10. Yang NN, Venugopalan M, Hardikar S et al. Correction: raloxifene response needs more than an element. Science. 1997; 275:1249. http://www.ncbi.nlm.nih.gov/pubmed/9064777?dopt=AbstractPlus
11. Pennisi E. Differing roles found for estrogen’s two receptors. Science. 1997; 277:1439. http://www.ncbi.nlm.nih.gov/pubmed/9304214?dopt=AbstractPlus
12. Paech K, Webb P, Kuiper GGJM et al. Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites. Science. 1997; 277:1508-10. http://www.ncbi.nlm.nih.gov/pubmed/9278514?dopt=AbstractPlus
13. Grese TA, Cho S, Finley DR et al. Structure-activity relationships of selective estrogen receptor modulators: modifications to the 2-arylbenzothiophene core of raloxifene. J Med Chem. 1997; 40:146-67. http://www.ncbi.nlm.nih.gov/pubmed/9003514?dopt=AbstractPlus
14. Brzozowski AM, Pike ACW, Dauter Z et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997; 389:753-8. http://www.ncbi.nlm.nih.gov/pubmed/9338790?dopt=AbstractPlus
15. Jones CD, Jevnikar MG, Pike AJ et al. Antiestrogens. 2. Structure-activity studies in a series of 3-aroyl-2-arylbenzo[b]thiophene derivatives leading to [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]-phenyl] methanone hydrochloride (LY156758), a remarkably effective estrogen antagonist with only minimal intrinsic estrogenicity. J Med Chem. 1984; 27:1057-66. http://www.ncbi.nlm.nih.gov/pubmed/6431104?dopt=AbstractPlus
16. Mitlak BH, Cohen FJ. In search of optimal long-term female hormone replacement: the potential of selective estrogen receptor modulators. Horm Res. 1997; 48:155-63. http://www.ncbi.nlm.nih.gov/pubmed/9378461?dopt=AbstractPlus
17. Bryant HU, Dere WH. Selective estrogen receptor modulators: an alternative to hormone replacement therapy. Proc Soc Exp Biol Med. 1998; 217:45-52. http://www.ncbi.nlm.nih.gov/pubmed/9421206?dopt=AbstractPlus
18. Baker VL, Draper M, Paul S et al. Reproductive endocrine and endometrial effects of raloxifene hydrochloride, a selective estrogen receptor modulator, in women with regular menstrual cycles. J Clin Endocrinol Metab. 1998; 83:6-13. http://www.ncbi.nlm.nih.gov/pubmed/9435408?dopt=AbstractPlus
19. Williams CL, Stancel GM. Estrogens and progestins. In: Hardman JG, Limbird LE, Molinoff PB et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill; 1995:1411-40.
20. Finkelstein JS. Osteoporosis. In: Bennett JC, Plum F, eds. Cecil textbook of medicine. 20th ed. Philadelphia: W.B. Saunders Company; 1996:1379-84.
21. Black LJ, Sato M, Rowley ER et al. Raloxifene (LY139481 HCl) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J Clin Invest. 1994; 93:63-9. http://www.ncbi.nlm.nih.gov/pubmed/8282823?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=293730&blobtype=pdf
22. Zuckerman SH, Bryan N. Inhibition of LDL oxidation and myeloperoxidase dependent tyrosyl radical formation by the selective estrogen receptor modulator raloxifene (LY139481 HCL). Atherosclerosis. 1996; 126:65-75. http://www.ncbi.nlm.nih.gov/pubmed/8879435?dopt=AbstractPlus
23. Draper MW, Flowers DE, Huster WJ et al. A controlled trial of raloxifene (LY139481) HCl: impact on bone turnover and serum lipid profile in healthy postmenopausal women. J Bone Miner Res. 1996; 11:835-42. http://www.ncbi.nlm.nih.gov/pubmed/8725181?dopt=AbstractPlus
24. Thomas JL, Braus PA. Coronary artery disease in women: a historical perspective. Arch Intern Med. 1998; 158:333-7. http://www.ncbi.nlm.nih.gov/pubmed/9487230?dopt=AbstractPlus
25. Cheskis BJ, Karathanasis S, Lyttle CR. Estrogen receptor ligands modulate its interaction with DNA. J Biol Chem. 1997; 272:11384-91. http://www.ncbi.nlm.nih.gov/pubmed/9111047?dopt=AbstractPlus
26. Fiorelli G, Martineti V, Gori F et al. Heterogeneity of binding sites and bioeffects of raloxifene on the human leukemic cell line FLG 29.1. Biochem Biophys Res Commun. 1997; 240:573-9. http://www.ncbi.nlm.nih.gov/pubmed/9398606?dopt=AbstractPlus
27. Dodge JA, Lugar CW, Cho S et al. Evaluation of the major metabolites of raloxifene as modulators of tissue selectivity. J Steroid Biochem Molec Biol. 1997; 61:97-106. http://www.ncbi.nlm.nih.gov/pubmed/9328215?dopt=AbstractPlus
28. Frolik CA, Bryant HU, Black EC et al. Time-dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: effects of raloxifene HCl, tamoxifen, estrogen, and alendronate. Bone. 1996; 18:621-7. http://www.ncbi.nlm.nih.gov/pubmed/8806005?dopt=AbstractPlus
29. Buzdar AU, Marcus C, Holmes F et al. Phase II evaluation of Ly156758 in metastatic breast cancer. Oncology. 1988; 45:344-5. http://www.ncbi.nlm.nih.gov/pubmed/3412740?dopt=AbstractPlus
30. Magee DE, Evans G, Sato M et al. Raloxifene (LY139481•HCl) does not antagonize the effects of estrogen on bone. J Bone Miner Res. 1996; 11:S446.
31. Heaney RP, Draper MW. Raloxifene and estrogen: comparative bone-remodeling kinetics. J Clin Endocrinol Metab. 1997; 82:3425-9. http://www.ncbi.nlm.nih.gov/pubmed/9329380?dopt=AbstractPlus
32. Powles TJ, Hickish T, Kanis JA et al. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol. 1996; 14:78-84. http://www.ncbi.nlm.nih.gov/pubmed/8558225?dopt=AbstractPlus
33. Ni L, Allerheiligen SRB, Basson R et al. Pharmacokinetics of raloxifene in men and postmenopausal women volunteers. Pharm Res. 1996; 13:S-430. http://www.ncbi.nlm.nih.gov/pubmed/8932457?dopt=AbstractPlus
34. Allerheiligen S, Geiser J, Knadler M et al. Raloxifene (RAL) pharmacokinetics and the associated endocrine effects in premenopausal women treated during the follicular, ovulatory, and luteal phases of the menstrual cycle. Pharm Res. 1996; 13:S-430.
35. Forgue ST, Rudy AC, Knadler MP et al. Raloxifene pharmacokinetics in healthy postmenopausal women. Pharm Res. 1996; 13:S-429.
36. Lindstrom TD, Whitaker NG, Whitaker GW. Disposition and metabolism of a new benzothiophene antiestrogen in rats, dogs and monkeys. Xenobiotica. 1984; 14:841-7. http://www.ncbi.nlm.nih.gov/pubmed/6506756?dopt=AbstractPlus
37. McDonnell DP, Clemm DL, Hermann T et al. Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol Endocrinol. 1995; 9:659-69. http://www.ncbi.nlm.nih.gov/pubmed/8592512?dopt=AbstractPlus
38. Katzenellenbogen BS, Montano MM, Le Goff P et al. Antiestrogens: mechanisms and actions in target cells. J Steroid Biochem Mol Biol. 1995; 53:387-93. http://www.ncbi.nlm.nih.gov/pubmed/7626486?dopt=AbstractPlus
39. Bass KM, Newschaffer CJ, Klag MJ et al. Plasma lipoprotein levels as predictors of cardiovascular death in women. Arch Intern Med. 1993; 153:2209-16. http://www.ncbi.nlm.nih.gov/pubmed/8215724?dopt=AbstractPlus
40. Seeman E. Osteoporosis: trials and tribulations. Am J Med. 1997; 103:74-89S. http://www.ncbi.nlm.nih.gov/pubmed/9236490?dopt=AbstractPlus
41. Wyeth Laboratories. Prempro (conjugated estrogens/medroxyprogesterone acetate) tablets prescribing information. In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2905-9.
42. Grey AB, Stapleton JP, Evans MC et al. The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women. Am J Med. 1995; 99:636-41. http://www.ncbi.nlm.nih.gov/pubmed/7503087?dopt=AbstractPlus
43. Bryant HU, Glasebrook AL, Yang NN et al. A pharmacological review of raloxifene. J Bone Miner Metab. 1996; 14:1-9.
44. Hosking D, Chilvers CED, Christiansen C et al et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. N Engl J Med. 1998; 338:485-92. http://www.ncbi.nlm.nih.gov/pubmed/9443925?dopt=AbstractPlus
45. Knadler MP, Lantz RJ, Gillespie TA et al. The disposition and metabolism of14C-labeled raloxifene in humans. Pharm Res. 1995; 12(Suppl):S-372.
46. Hol T, Cox MB, Bryant HU et al. Selective estrogen receptor modulators and postmenopausal women’s health. J Womens Health. 1997; 6:523-31. http://www.ncbi.nlm.nih.gov/pubmed/9356975?dopt=AbstractPlus
47. Hannover Bjarnason N, Haarbo J, Byrjalsen I et al. Raloxifene inhibits aortic accumulation of cholesterol in ovariectomized, cholesterol-fed rabbits. Circulation. 1997; 96:1964-9. http://www.ncbi.nlm.nih.gov/pubmed/9323087?dopt=AbstractPlus
48. Scheele WH, Symanowski SM, Neale S et al. Raloxifene does not cause stimulatory effects on the uterus in healthy postmenopausal women. In: The Endocrine Society 79th annual meeting program, Minneapolis 1997 Jun 11–14. The Endocrine Society Press: Bethesda, MD; p. 498. Abstract No. P3-246.
49. Gunness M, Prestwood K, Lu Y et al. Histomorphometric, bone marker, and bone mineral density response to raloxifene HCl and premarin in postmenopausal women. In: The Endocrine Society 79th annual meeting program, Minneapolis 1997 Jun 11–14. The Endocrine Society Press: Bethesda, MD; p. 67. Abstract No. OR4-2.
50. Evans G, Bryant HU, Magee D et al. The effects of raloxifene on tibia histomorphometry in ovariectomized rats. Endocrinology. 1994; 134:2283-8. http://www.ncbi.nlm.nih.gov/pubmed/8156931?dopt=AbstractPlus
51. Ajzenberg N, Depraetere H, Girma JP et al. Platelet aggregation induced by a monoclonal antibody to von Willebrand factor. Atherosclerosis. 1997; 134:182.
52. Eli Lilly and Company. Evista (raloxifene hydrochloride) tablets information for the patient. Indianapolis, IN; 1997 Dec 10.
53. Lufkin EG, Whitaker MD, Argueta R et al. Raloxifene treatment of postmenopausal osteoporosis. J Bone Miner Res. 1997; 12:S150.
54. Gize EA, Venugopalan M, Glasebrook AL et al. Characterization of raloxifene binding and transactivation properties of the estrogen receptor-beta (ERβ). J Bone Miner Res. 1997; 12:S460.
55. Anon. Raloxifene for postmenopausal osteoporosis. Med Lett Drug Ther. 1998; 40:29-30.
56. Goldberg RM, Loprinzi CL, O’Fallon JR et al. Transdermal clonidine for ameliorating tamoxifen-induced hot flashes. J Clin Oncol. 1994; 12:155-8. http://www.ncbi.nlm.nih.gov/pubmed/8270972?dopt=AbstractPlus
57. Food and Drug Administration. Prescription drug advertising; content and format for labeling of human prescription drugs. Fed Regist. 1979; 44:37434-67.
58. Hoyt JA, Fisher LF, Buelke-Sam JL et al. The selective estrogen receptor modulator, raloxifene: reproductive assessments following premating exposure in female rats. Teratology. 1996; 53:103.
59. Hoyt JA, Fisher LF, Swisher DK et al. The selective estrogen receptor modulator, raloxifene: reproductive assessments in male rats. Teratology. 1996; 53:103.
60. Clarke DO, Griffey KI, Buelke-Sam JL et al. The selective estrogen receptor modulator, raloxifene: reproductive assessments following preimplantation exposure in mated female rats. Teratology. 1996; 53:103-4.
61. Byrd RA, Francis PC. The selective estrogen receptor modulator, raloxifene: segment II studies in rats and rabbits. Teratology. 1996; 53:104.
62. Buelke-Sam J, Griffey KI, Schwier PW et al. The selective estrogen receptor modulator, raloxifene: a segment II/III delivery study in rats. I - maternal and preweaning offspring assessments. Teratology. 1996; 53:104.
63. Buelke-Sam J, Cohen I, Wierda D et al. The selective estrogen receptor modulator, raloxifene: a segment II/III delivery study in rats. II - postweaning offspring assessments. Teratology. 1996; 53:104.
64. McDonnell DP. Definition of the molecular mechanism of action of tissue-selective oestrogen-receptor modulators. Biochem Soc Transact. 1998; 26:54-60.
65. Gray JM, Ziemian L. Antiestrogen binding sites in brain and pituitary of ovariectomized rats. Brain Res. 1992; 578:55-60. http://www.ncbi.nlm.nih.gov/pubmed/1511289?dopt=AbstractPlus
66. Eli Lilly and Company. Dear healthcare professional letter regarding questioning the safety of Evista (raloxifene hydrochloride). Indianapolis, IN: Eli Lilly and Company; 1998 Feb.
67. Eli Lilly and Company. Product information form for American hospital formulary service: Evista (raloxifene hydrochloride). Indianapolis, IN; 1998 Mar 31.
68. National Cancer Institute. Breast cancer prevention trial shows major benefit, some risk. Bethesda, MD; 1998 Apr 6. Press release.
69. Balfour JA, Goa KL. Raloxifene. Drugs Aging. 1998; 12:335-41. http://www.ncbi.nlm.nih.gov/pubmed/9571395?dopt=AbstractPlus
70. Kauffman RF, Bensch WR, Roudebush RE et al. Hypocholesterolemic activity of raloxifene (LY139481): pharmacological characterization as a selective estrogen receptor modulator. J Pharmacol Exp Ther. 1997; 280:146-53. http://www.ncbi.nlm.nih.gov/pubmed/8996192?dopt=AbstractPlus
71. Burton TM. New drugs give cause for hope in fight against breast cancer: preventive therapies show promise, but the testing has a long way to go: Lilly looks beyond Prozac. Wall Street J. 1998 20 Apr.
72. Delmas PD, Mitlak BH, Christiansen C. Effects of Raloxifene in Postmenopausal Women. N Engl J Med. 1998; 338:1313.
73. Wiznitzer I, Benz C. Tamoxifen vs. LY156758 for treatment of human breast and prostate cancer in vitro. Breast Cancer Res Treat. 1983; 3:305.
74. Sato M, Glasebrook AL, Bryant HU. Raloxifene: a selective estrogen receptor modulator. J Bone Miner Metab. 1995; 12(Suppl II):S9-20.
75. Labrie F, Veilleux R, Fournier A. Glucocorticoids stimulate the growth of mouse mammary carcinoma Shionogi cells in culture. Mol Cell Endocrinol. 1988; 58:207-11. http://www.ncbi.nlm.nih.gov/pubmed/2850248?dopt=AbstractPlus
76. Thompson EW, Reich R, Shima TB et al. Differential regulation of growth and invasiveness of MCF-7 breast cancer cells by antiestrogens. Cancer Res. 1988; 48:6764-8. http://www.ncbi.nlm.nih.gov/pubmed/2846159?dopt=AbstractPlus
77. Gottardis MM, Jordan VC. Antitumor actions of keoxifene and tamoxifen in the N-nitrosomethylurea-induced rat mammary carcinoma model. Cancer Res. 1987; 47:4020-4. http://www.ncbi.nlm.nih.gov/pubmed/3607747?dopt=AbstractPlus
78. European Foundation for Osteoporosis and Bone Disease, National Osteoporosis Foundation, and National Institute of Arthritis and Muscoloskeletal and Skin Diseases. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993; 94:646-50. http://www.ncbi.nlm.nih.gov/pubmed/8506892?dopt=AbstractPlus
79. Commonwealth Department of Health and Family Services, Australian National Consensus Conference 1996. The prevention and management of osteoporosis: consensus atatement. Med J Austral. 1997; 167(suppl):S1-15.
80. Osteoporosis Society of Canada Scientific Advisory Board. Clinical practice guidelines for diagnosis and mangement of osteoporosis. CMAJ. 1996; 155:1113-33. http://www.ncbi.nlm.nih.gov/pubmed/8873639?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1335371&blobtype=pdf
81. Ross PD. Osteoporosis: frequency, consequences, and risk factors. Arch Intern Med. 1996; 156:1399-411. http://www.ncbi.nlm.nih.gov/pubmed/8678708?dopt=AbstractPlus
82. Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med. 1998; 338:736-46. http://www.ncbi.nlm.nih.gov/pubmed/9494151?dopt=AbstractPlus
83. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press; 1997. (Uncorrected proofs.)
84. Cauley JA, Seeley DG, Ensrud K et al. Estrogen replacement therapy and fractures in older women. Ann Intern Med. 1995; 122:9-16. http://www.ncbi.nlm.nih.gov/pubmed/7985914?dopt=AbstractPlus
85. Schneider DL, Barrett-Connor LB, Morton DJ. Tming of postmenopausal estrogen for optimal bone mineral density: the Racncho Bernardo study. JAMA. 1997; 277:543-7. http://www.ncbi.nlm.nih.gov/pubmed/9032160?dopt=AbstractPlus
86. Maricic M. Early prevention vs late treatment for osteoporosis. Arch Intern Med. 1997; 157:2545-6. http://www.ncbi.nlm.nih.gov/pubmed/9531221?dopt=AbstractPlus
87. Heaney RP. Bone mass, bone loss, and osteoporosis prophylaxis. Ann Intern Med. 1998; 128:313-4. http://www.ncbi.nlm.nih.gov/pubmed/9471936?dopt=AbstractPlus
88. Walsh BW, Kuller LH, Wild RA et al. Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women. JAMA. 1998; 279:1445-51. http://www.ncbi.nlm.nih.gov/pubmed/9600478?dopt=AbstractPlus
89. Rifkind BM, Rossouw JE. Of designer drugs, magic bullets, and gold standards. JAMA. 1998; 279:1483-5. http://www.ncbi.nlm.nih.gov/pubmed/9600485?dopt=AbstractPlus
90. Powles TJ, Hickish T, Kanis JA et al. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol. 1996; 14:78-84. http://www.ncbi.nlm.nih.gov/pubmed/8558225?dopt=AbstractPlus
91. Reviewers’ comments (personal observations).
92. Jordan VC, Glusman JE, Eckert S et al. Incident primary breast cancers are reduced by raloxifene: integrated data from multicenter, double-blind, randomized trials in 12,000 postmenopausal women. Proc Am Soc Clin Oncol. 1998; 17:122A.
93. Cummings SR, Eckert S, Krueger KA et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. JAMA. 1999; 281:2189-97. http://www.ncbi.nlm.nih.gov/pubmed/10376571?dopt=AbstractPlus
94. Gradishar WJ, Glusman JE, Vogel CL et al. Raloxifene HCl, a new endocrine agent, is active in estrogen receptor positive (ER+) metastatic breast cancer. Breast Cancer Research and Treatment; 20th Annual San Antonio Breast Cancer Symposium; 1997 Dec 3-6; San Antonio. Dordrecht/Boston/London: Kluwer Academic Publishers. Changes and additions to program. Abstract 209.
95. Gluer CC, Cummings SR, Bauer DC et al. Osteoporosis: assocation of recent fractures with quatititative US findings. Radiology. 1996; 199:725-32. http://www.ncbi.nlm.nih.gov/pubmed/8637996?dopt=AbstractPlus
96. Eli Lilly and Company, Indianapolis, IN: Personal communication.
97. Vilches AR, Pérez V, Suchecki DE. Raloxifene-associated hepatitis. Lancet. 1998; 352:1524-5. http://www.ncbi.nlm.nih.gov/pubmed/9820309?dopt=AbstractPlus
98. Ettinger B, Black DM, Mitlak BH et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA. 1999; 282:637-45. http://www.ncbi.nlm.nih.gov/pubmed/10517716?dopt=AbstractPlus
99. McClung MR. Therapy for fracture prevention. JAMA. 1999; 282:687-9. http://www.ncbi.nlm.nih.gov/pubmed/10517723?dopt=AbstractPlus
100. Cauley JA, Norton L, Lippman ME et al. Continued breast cancer reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Breast Ca Res Treat. 2001; 65:125-34.
101. Khovidhunkit W, Shoback DM. Clinical effects of raloxifene hydrochloride in women. Ann Intern Med. 1999; 130:431-9. http://www.ncbi.nlm.nih.gov/pubmed/10068418?dopt=AbstractPlus
102. Chlebowski RT, Col N, Winer EP at al. American Society of Clinical Oncology technology assessment of pharmacologic interventions for breast cancer risk reduction including tamoxifen, raloxifene, and aromatase inhibition. J Clin Oncol. 2002; 20:3328-43. http://www.ncbi.nlm.nih.gov/pubmed/12149307?dopt=AbstractPlus
103. Committee on Educational Bulletins of the American College of obstetricians and Gynecologists. ACOG Educational Bulletin: osteoporosis. Obstet Gynecol. 1998; 91:1-9. http://www.ncbi.nlm.nih.gov/pubmed/9464711?dopt=AbstractPlus
104. Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med. 1998; 338:736-46. http://www.ncbi.nlm.nih.gov/pubmed/9494151?dopt=AbstractPlus
105. Cosman F, de Beur SJ, LeBoff MS et al. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014; 25:2359-81. http://www.ncbi.nlm.nih.gov/pubmed/25182228?dopt=AbstractPlus
106. Watts NB, Bilezikian JP, Camacho PM et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2010 Nov-Dec; 16 Suppl 3:1-37. http://www.ncbi.nlm.nih.gov/pubmed/21224201?dopt=AbstractPlus
108. Anon. Drugs for prevention and treatment of postmenopausal osteoporosis. Med Lett Drugs Ther. 2000; 42:97-100. http://www.ncbi.nlm.nih.gov/pubmed/11035622?dopt=AbstractPlus
109. National Cancer Institute (NCI). Questions & answers: the study of tamoxifen and raloxifene (STAR). Bethesda, MD. 2002 May 17.
110. Vogel VG, Costantino JP, Wickerham DL et al. The study of tamoxifen and raloxifene: preliminary enrollment data from a randomized breast cancer risk reduction trial. Clin Breast Cancer. 2002; 3:153-9. http://www.ncbi.nlm.nih.gov/pubmed/12123540?dopt=AbstractPlus
111. American College of Obstetricians and Gynecologists. Questions and answers on hormone replacement therapy. Washington DC; August 2002. From the American College of Obstetricians and Gynecologists web site (http://www.acog.org).
112. U.S. Preventive Services Task Force. Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: recommendations and rationale. Ann Intern Med. 2002; 137:834-9.
113. Vogel VG, Costantino JP, Wickerham DL for the National Surgical Adjuvant Breast and Bowel Project (NSABP). Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP study of tamoxifen and raloxifene (STAR) P-2 trial. JAMA. 2006; 295:2727-41. http://www.ncbi.nlm.nih.gov/pubmed/16754727?dopt=AbstractPlus
114. Martino S, Cauley JA, Barrett-Connor E for the CORE Investigators. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 2004; 96:1751-61. http://www.ncbi.nlm.nih.gov/pubmed/15572757?dopt=AbstractPlus
115. Barrett-Connor E, Mosca L, Collins P for the Raloxifene use for the heart (RUTH) trial investigators. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006; 355:125-37. http://www.ncbi.nlm.nih.gov/pubmed/16837676?dopt=AbstractPlus
116. Prestwood KM, Gunness M, Muchmore DB et al. A comparison of the effects of raloxifene and estrogen on bone in postmenopausal women. J Clin Endocrinol Metab. 2000; 85:2197-202. http://www.ncbi.nlm.nih.gov/pubmed/10852452?dopt=AbstractPlus
117. Visvanathan K, Chlebowski RT, Hurley P et al. American society of clinical oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J Clin Oncol. 2009; 27:3235-58. http://www.ncbi.nlm.nih.gov/pubmed/19470930?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2716943&blobtype=pdf
118. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. Version 2.2009. From the NCCN website at:http://www.nccn.org/professionals/physician_gls/PDF/breast_risk.pdf.
119. Breast Cancer Risk Assessment Tool. From the National Cancer Institute website at: http://www.cancer.gov/bcrisktool/. Accessed Sept 2009.
120. Land SR, Wickerham DL, Costantino JP et al. Patient-reported symptoms and quality of life during treatment with tamoxifen or raloxifene for breast cancer prevention: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006; 295:2742-51. http://www.ncbi.nlm.nih.gov/pubmed/16754728?dopt=AbstractPlus
622. Buckley L, Guyatt G, Fink HA et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatol. 2017; 69:1521-1537. http://www.ncbi.nlm.nih.gov/pubmed/28585373?dopt=AbstractPlus
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