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
Increased risk for DVT and pulmonary embolism.1 Contraindicated in women with active or past episodes of venous thrombosis.1 (See Contraindications and Cardiovascular Effects under Cautions.)
Increased risk of fatal stroke reported in women with CHD or increased risk for CHD.1 Weigh risks versus benefits in women at risk for stroke.1 (See Cardiovascular Effects under Cautions.)
Estrogen agonist-antagonist; a nonsteroidal benzothiophene derivative.1 2 3 13 14 15 16 17 55 69 70
Uses for Raloxifene Hydrochloride
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
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
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
Raloxifene Hydrochloride Dosage and Administration
Administer orally once daily without regard to meals or time of day.1 2 55
Available as raloxifene hydrochloride; dosage expressed in terms of the salt.1
Prevention in Postmenopausal WomenOral
60 mg daily.1 2 55
Treatment in Postmenopausal WomenOral
60 mg daily.1 98
Reduction in the Incidence of Invasive Breast CancerOral
60 mg daily.1 Optimum duration of therapy unknown.1
Cautions for Raloxifene Hydrochloride
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
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
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
Not indicated.1 Safety not established.1
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
Investigate unexplained breast abnormality.1 Does not eliminate risk of breast cancer.1
Use in Men
Safety and efficacy not evaluated.1
Not associated with endometrial proliferation.1 Investigate unexplained uterine bleeding.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
Hot flushes (flashes), leg cramps, peripheral edema, flu-like syndrome, arthralgia, sweating.1 2 23 69 72 88 93 96 98
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
Concomitant administration with cholestyramine not recommended1 52
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
Rapidly absorbed from GI tract; 60% of an oral dose is absorbed, but absolute bioavailability as unchanged drug is only 2% because of extensive first-pass glucuronidation.1 27 33 34 35 45 69
Following oral administration, peak plasma concentrations achieved at 6 hours (raloxifene) and 1 hour (glucuronide conjugates).33 35
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
Raloxifene and its monoglucuronide conjugates: >95%.1 69 96 Raloxifene binds to albumin and α1-acid glycoprotein but not to testosterone-estradiol binding globulin (sex hormone binding globulin).1
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
Excreted principally in feces as unabsorbed drug and via biliary elimination as glucuronide conjugates (subsequently metabolized by bacteria in GI tract to the parent drug).1 45 55 69 96
32.5 hours.1 55
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
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.
AHFS DI Essentials. © Copyright 2017, Selected Revisions April 1, 2008. 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; 2007 Sep.
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. [PubMed 9385122]
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. [PubMed 9423751]
4. Gradishar WJ, Jordan VC. Clinical potential of new antiestrogens. J Clin Oncol. 1997; 15:840-52. [PubMed 9053512]
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. [PubMed 9385130]
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. [PubMed 8787121]
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. [PubMed 8703055]
10. Yang NN, Venugopalan M, Hardikar S et al. Correction: raloxifene response needs more than an element. Science. 1997; 275:1249. [PubMed 9064777]
11. Pennisi E. Differing roles found for estrogen’s two receptors. Science. 1997; 277:1439. [PubMed 9304214]
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. [PubMed 9278514]
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. [PubMed 9003514]
14. Brzozowski AM, Pike ACW, Dauter Z et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997; 389:753-8. [PubMed 9338790]
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. [PubMed 6431104]
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. [PubMed 9378461]
17. Bryant HU, Dere WH. Selective estrogen receptor modulators: an alternative to hormone replacement therapy. Proc Soc Exp Biol Med. 1998; 217:45-52. [PubMed 9421206]
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. [PubMed 9435408]
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. [PubMed 8282823]
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. [PubMed 8879435]
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. [PubMed 8725181]
24. Thomas JL, Braus PA. Coronary artery disease in women: a historical perspective. Arch Intern Med. 1998; 158:333-7. [PubMed 9487230]
25. Cheskis BJ, Karathanasis S, Lyttle CR. Estrogen receptor ligands modulate its interaction with DNA. J Biol Chem. 1997; 272:11384-91. [PubMed 9111047]
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. [PubMed 9398606]
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. [PubMed 9328215]
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. [PubMed 8806005]
29. Buzdar AU, Marcus C, Holmes F et al. Phase II evaluation of Ly156758 in metastatic breast cancer. Oncology. 1988; 45:344-5. [PubMed 3412740]
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. [PubMed 9329380]
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. [PubMed 8558225]
33. Ni L, Allerheiligen SRB, Basson R et al. Pharmacokinetics of raloxifene in men and postmenopausal women volunteers. Pharm Res. 1996; 13:S-430. [PubMed 8932457]
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. [PubMed 6506756]
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. [PubMed 8592512]
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. [PubMed 7626486]
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. [PubMed 8215724]
40. Seeman E. Osteoporosis: trials and tribulations. Am J Med. 1997; 103:74-89S. [PubMed 9236490]
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. [PubMed 7503087]
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. [PubMed 9443925]
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. [PubMed 9356975]
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. [PubMed 9323087]
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. [PubMed 8156931]
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. [PubMed 8270972]
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. [PubMed 1511289]
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. [PubMed 9571395]
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. [PubMed 8996192]
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. [PubMed 2850248]
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. [PubMed 2846159]
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. [PubMed 3607747]
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. [PubMed 8506892]
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. [PubMed 8873639]
81. Ross PD. Osteoporosis: frequency, consequences, and risk factors. Arch Intern Med. 1996; 156:1399-411. [PubMed 8678708]
82. Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med. 1998; 338:736-46. [PubMed 9494151]
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. [PubMed 7985914]
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. [PubMed 9032160]
86. Maricic M. Early prevention vs late treatment for osteoporosis. Arch Intern Med. 1997; 157:2545-6. [PubMed 9531221]
87. Heaney RP. Bone mass, bone loss, and osteoporosis prophylaxis. Ann Intern Med. 1998; 128:313-4. [PubMed 9471936]
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. [PubMed 9600478]
89. Rifkind BM, Rossouw JE. Of designer drugs, magic bullets, and gold standards. JAMA. 1998; 279:1483-5. [PubMed 9600485]
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. [PubMed 8558225]
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. [PubMed 10376571]
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. [PubMed 8637996]
96. Eli Lilly and Company, Indianapolis, IN: Personal communication.
97. Vilches AR, Pérez V, Suchecki DE. Raloxifene-associated hepatitis. Lancet. 1998; 352:1524-5. [PubMed 9820309]
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. [PubMed 10517716]
99. McClung MR. Therapy for fracture prevention. JAMA. 1999; 282:687-9. [PubMed 10517723]
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. [PubMed 10068418]
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. [PubMed 12149307]
103. Committee on Educational Bulletins of the American College of obstetricians and Gynecologists. ACOG Educational Bulletin: osteoporosis. Obstet Gynecol. 1998; 91:1-9. [PubMed 9464711]
104. Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med. 1998; 338:736-46. [PubMed 9494151]
105. National Osteoporosis Foundation. Physician’s guide to prevention and treatment of osteoporosis. Washington, DC; 1998.
106. World Health Organization. Guidelines for preclinical evaluation and clinical trials in osteoporosis. Geneva: World Health Organization; 1998:5-6.
107. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-induced Osteoporosis. Recommendations for the prevention and treatment of gluococorticoid-induced osteoporosis: 2001 update. Arthritis Rheum. 2001; 44:1496-503. [PubMed 11465699]
108. Anon. Drugs for prevention and treatment of postmenopausal osteoporosis. Med Lett Drugs Ther. 2000; 42:97-100. [PubMed 11035622]
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. [PubMed 12123540]
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 ().
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. [PubMed 16754727]
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. [PubMed 15572757]
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. [PubMed 16837676]
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. [PubMed 10852452]
More about raloxifene
- Side Effects
- During Pregnancy
- Dosage Information
- Drug Images
- Drug Interactions
- Support Group
- Pricing & Coupons
- En Español
- 5 Reviews – Add your own review/rating
- Drug class: hormones/antineoplastics
Other brands: Evista