Raloxifene

drugbox
IUPAC_name = [6-hydroxy-2-(4-hydroxyphenyl)- benzothiophen-3-yl] - [4- [2-(1-piperidyl)ethoxy] phenyl] -methanone

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CAS_number = 84449-90-1
ATC_prefix = G03
ATC_suffix = XC01
PubChem = 5035
DrugBank = APRD00400
C = 28 | H = 27 | N = 1 | O = 4 | S = 1
molecular_weight = 473.584 g/mol
smiles = Oc1ccc(cc1)c1sc2cc(O)ccc2c1C(=O)c1ccc(OCCN2CCCCC2)cc1
bioavailability = 2%
protein_bound = 95%
metabolism = Hepatic glucuronidation
CYP system not involved
elimination_half-life = 27.7 hours
excretion = Fecal
licence_EU = Evista
licence_US = Evista
pregnancy_AU = X
pregnancy_US = X
legal_status = Rx-only
routes_of_administration = Oral

Raloxifene 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. It was announced on April 17, 2006, that raloxifene is as effective as tamoxifen in reducing the incidence of breast cancer in certain high risk groups of females, [http://www.cancer.gov/clinicaltrials/digestpage/STAR/page2] though with a reduced risk of thromboembolic events and cataracts in patients taking raloxifene versus those taking tamoxifen. [cite journal | first = Victor | last = Vogel | coauthors = Joseph Constantino, Lawrence Wickerman "et al." | title = Effects of Tamoxifen vs. Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes | journal = The Journal of the American Medical Association | volume = 295 | issue = 23 | pages = 2727–2741 | doi = 10.1001/jama.295.23.joc60074 | year = 2006 | pmid = 16754727] 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. [cite press release |title=FDA Approves New Uses for Evista
publisher=U.S. Food and Drug Administration |date=2007-09-14 |url=http://www.fda.gov/bbs/topics/NEWS/2007/NEW01698.html |accessdate=2007-09-15]

There has been criticism in the mainstream oncology press of the way that information about the drug was released. [cite journal | author = Thelancetoncology,| title = A STARring role for raloxifene? | journal = Lancet Oncol | volume = 7 | issue = 6 | pages = 443 | year = 2006 | pmid = 16750489| doi = 10.1016/S1470-2045(06)70701-X] There has been some confusion in the lay media about the meaning of the trial results. There is no specific clinical evidence for the use of raloxifene in the adjuvant treatment of breast cancer over established drugs such as tamoxifen or anastrozole.fact|date=September 2007

Raloxifene is produced by Eli Lilly and Company and is sold under the brand name Evista.

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 [... finish the sentence ...]

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, and for reduction in risk of invasive breast cancer in postmenopausal women at high risk for invasive breast cancer.

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.fact|date=September 2007

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.

As cancer drug

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. [cite journal | author = Lisa Nainggolan| title = A balancing act: The pro and cons of raloxefene | url = http://www.theheart.org/article/722709.do | volume = | issue = | pages = | date = July 12, 2006 ]

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. [cite journal | author = Barrett-Connor E, Mosca L, Collins P, et al | title = Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women | journal ="New England Journal of Medicine" | volume = 355 | issue = | pages = 125–137 | year = 2006 | doi = 10.1056/NEJMoa062462 | pmid = 16837676 ]

On September 14, 2007, Steven K. Galson, then 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. [ [http://afp.google.com/article/ALeqM5iN5TpHWbHfPZMBgXvaIyVlgc-XZQ AFP.google.com, US approves Lilly's Evista for breast cancer prevention] ]

References

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External links

* [http://www.nsabp.pitt.edu/STAR/Index.html STAR: a head-to-head comparison of tamoxifen and raloxifene as breast-cancer preventatives]
* [http://pi.lilly.com/us/evista-pi.pdf Full Prescribing Information]
* [http://www.nwhn.org/publications/position_details.php?poid=5 Position paper of the National Women's Health Network]