Raloxifene

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Raloxifene
File:Raloxifene.png
Systematic (IUPAC) name
[6-hydroxy-2-(4-hydroxyphenyl)- benzothiophen-3-yl]- [4-[2-(1-piperidyl)ethoxy]phenyl] -methanone
Clinical data
[[Regulation of therapeutic goods |Template:Engvar data]]
Pregnancy
category
  • AU: X (High risk)
  • US: X (Contraindicated)
Routes of
administration
Oral
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 2%
Protein binding 95%
Metabolism Hepatic glucuronidation
CYP system not involved
Biological half-life 27.7 hours
Excretion Fecal
Identifiers
CAS Number 84449-90-1
ATC code G03XC01 (WHO)
PubChem CID 5035
DrugBank APRD00400
Chemical data
Formula C28H27NO4S
Molar mass 473.584 g/mol[[Script error: No such module "String".]]
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Raloxifene (marketed as Evista by Eli Lilly and Company) is an oral selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. It is used in the prevention of osteoporosis in postmenopausal women.

In 2006, the National Cancer Institute announced that raloxifene was as effective as tamoxifen in reducing the incidence of breast cancer in postmenopausal women at increased risk. A major adverse effect of tamoxifen is uterine cancer; raloxifene had fewer uterine cancers. Tamoxifen increased the risk of cataracts, but raloxifene did not. Both groups had more blood clots in veins and the lungs, but that side effect was more common with tamoxifen than raloxifene.[1][2][3] On September 14, 2007, the U.S. Food and Drug Administration announced approval of raloxifene for reducing the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer.[4]

An editorial in Lancet Oncology criticized the way that information about the drug was released.[5]

Description

Raloxifene hydrochloride (HCl) has the empirical formula C28H27NO4S•HCl, which corresponds to a molecular weight of 510.05 g/mol. Raloxifene HCl is an off-white to pale-yellow solid that is slightly soluble in water.

SERMs mimic estrogen in some tissues and have anti-estrogen activity in others. Other SERMs, such as Pfizer's lasofoxifene and Wyeth's bazedoxifene are in the later development phases.

Indication

Raloxifene is indicated for the treatment and prevention of osteoporosis in postmenopausal women, for reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis. For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate.

Contraindications and precautions

Raloxifene is contraindicated in lactating women or women who are or may become pregnant, in women with active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis and in women known to be hypersensitive to raloxifene.

Adverse reactions

Common adverse events considered to be drug-related were hot flashes and leg cramps.[citation needed]

Raloxifene may infrequently cause serious blood clots to form in the legs, lungs, or eyes. Other reactions experienced include leg swelling/pain, trouble breathing, chest pain, vision changes. Raloxifene is a teratogenic drug.

In a 2006 study published in New England Journal of Medicine, raloxifene produced significantly more strokes and blood clots than the placebo.[6]

A report in September 2009 from Health and Human Services' Agency for Healthcare Research and Quality suggests that tamoxifen, raloxifene, and tibolone used to treat breast cancer significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects.[7]

As cancer drug

File:Rolaxifene.jpg
Bottle of Raloxifene

Raloxifene reduces the risk of hormone-positive breast cancer and vertebral fractures "without a shadow of a doubt," but its effects on cardiovascular disease remain less certain, according to the results of the "Raloxifene for Use of the Heart" (RUTH) study published in the July 13, 2006 issue of the New England Journal of Medicine by Dr. Elizabeth Barrett-Connor (University of California at San Diego) and colleagues.[8]

In the trial, in women with coronary heart disease (CHD) or multiple risk factors for CHD, raloxifene had no significant effect on the primary end point, coronary events, but it did significantly increase the risk of venous thromboembolism (VTE). And although the drug had no effect on stroke, there was a seemingly paradoxical significant increase in death from stroke.[9]

On September 14, 2007, Steven K. Galson, the director of the United States Food and Drug Administration's Center for Drug Evaluation and Research announced authorization of the sale of raloxifene to prevent invasive breast cancer in post-menopausal women.[10]

Chemical Synthesis

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Jones, Charles D.; Jevnikar, Mary G.; Pike, Andrew J.; Peters, Mary K.; Black, Larry J.; Thompson, Allen R.; Falcone, Julie F.; Clemens, James A. (1984). "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 (LY 156758), a remarkably effective estrogen antagonist with only minimal intrinsic estrogenicity". Journal of Medicinal Chemistry. 27 (8): 1057. doi:10.1021/jm00374a021. PMID 6431104. 

References

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External links

cs:Raloxifen

de:Raloxifen hu:Raloxifen it:Raloxifene

pl:Raloksifen
  1. Study of Tamoxifen and Raloxifene (STAR) Trial Cancer.gov
  2. Results of the Study of Tamoxifen and Raloxifene (STAR) Released: Osteoporosis Drug Raloxifene Shown to be as Effective as Tamoxifen in Preventing Invasive Breast Cancer (Press Release) 06/21/2006
  3. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  4. "FDA Approves New Uses for Evista" (Press release). U.S. Food and Drug Administration. 2007-09-14. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01698.html. Retrieved 2007-09-15. 
  5. Thelancetoncology, (2006). "A STARring role for raloxifene?". Lancet Oncol. 7 (6): 443. doi:10.1016/S1470-2045(06)70701-X. PMID 16750489. 
  6. [http://content.nejm.org/cgi/content/full/355/2/125 355:125-137, July 13, 2006, Effects of Raloxifene on Cardiovascular Events and Breast Cancer in Postmenopausal Women Elizabeth Barrett-Connor, Lori Mosca,Peter Collins, et al. for the Raloxifene Use for The Heart (RUTH) Trial Investigators [Free full text]
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  8. Lisa Nainggolan (July 12, 2006). "A balancing act: The pro and cons of raloxefene". 
  9. Barrett-Connor E, Mosca L, Collins P; et al. (2006-07-13). "Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women". New England Journal of Medicine. 355 (2): 125–137. doi:10.1056/NEJMoa062462. PMID 16837676. 
  10. AFP.google.com, US approves Lilly's Evista for breast cancer prevention