Raloxifene
Encyclopedia
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.
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. 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.
An editorial in Lancet Oncology criticized the way that information about the drug was released.
(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.
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.
s, including deep vein thrombosis
, pulmonary embolism
, and retinal vein thrombosis and in women known to be hypersensitive to raloxifene.
es and leg cramp
s.
Raloxifene may infrequently cause serious blood clot
s 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.
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.
by Dr. Elizabeth Barrett-Connor (University of California at San Diego) and colleagues.
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.
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.
Selective estrogen receptor modulator
Selective Estrogen Receptor Modulators are a class of compounds that act on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively...
(SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. It is used in the prevention of osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
in postmenopausal women.
In 2006, the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
announced that raloxifene was as effective as tamoxifen
Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
in reducing the incidence of breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
in postmenopausal women at increased risk. A major adverse effect of tamoxifen is uterine cancer
Uterine cancer
The term uterine cancer may refer to any of several different types of cancer which occur in the uterus, namely:*Uterine sarcomas: sarcomas of the myometrium, or muscular layer of the uterus, are most commonly leiomyosarcomas.*Endometrial 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. 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.
An editorial in Lancet Oncology criticized the way that information about the drug was released.
Description
Raloxifene hydrochlorideHydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
(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
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
lasofoxifene
Lasofoxifene
Lasofoxifene is a non-steroidal selective estrogen receptor modulator which is under development by Pfizer for the prevention and treatment of osteoporosis and for the treatment of vaginal atrophy, and the result of an exclusive research collaboration with Ligand Pharmaceuticals .In September...
and Wyeth's
Wyeth
Wyeth, formerly one of the companies owned by American Home Products Corporation , was a pharmaceutical company. The company was based in Madison, New Jersey, USA...
bazedoxifene
Bazedoxifene
Bazedoxifene is a third generation selective estrogen receptor modulator , under development by Pfizer following the completion of their takeover of Wyeth Pharmaceuticals. Pfizer are seeking approval for bazedoxifene in the prevention and treatment of postmenopausal osteoporosis...
are in the later development phases.
Indication
Raloxifene is indicated for the treatment and prevention of osteoporosisOsteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
in postmenopausal
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
women, for reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis.
For either osteoporosis treatment or prevention, supplemental calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
and/or vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
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 eventThrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
s, including deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
, pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
, 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 flashHot flush
Hot flashes are a symptom of the changing hormone levels that are considered to be characteristic of menopause.- Presentation :...
es and leg cramp
Cramp
Cramps are unpleasant, often painful sensations caused by muscle contraction or over shortening. Common causes of skeletal muscle cramps include muscle fatigue, low sodium, and low potassium...
s.
Raloxifene may infrequently cause serious blood clot
Thrombus
A thrombus , or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system...
s 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.
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.
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 MedicineNew England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
by Dr. Elizabeth Barrett-Connor (University of California at San Diego) and colleagues.
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.
On September 14, 2007, Steven K. Galson
Steven K. Galson
Steven Kenneth Galson is an American public health physician. He is a retired rear admiral in the United States Public Health Service Commissioned Corps and public health administrator who served as the acting Surgeon General of the United States from October 1, 2007 – October 1, 2009...
, the director of the United States Food and Drug Administration's Center for Drug Evaluation and Research
Center for Drug Evaluation and Research
The Center for Drug Evaluation and Research is a division of the U.S. Food and Drug Administration that monitors most drugs as defined in the Food, Drug, and Cosmetic Act. Some biological products are also legally considered drugs, but they are covered by the Center for Biologics Evaluation and...
announced authorization of the sale of raloxifene to prevent invasive breast cancer in post-menopausal women.
Chemical synthesis
External links
- STAR: a head-to-head comparison of tamoxifen and raloxifene as breast-cancer preventatives
- Full Prescribing Information
- http://www.nwhn.org/publications/position_details.php?poid=5Position paper of the National Women's Health NetworkNational Women's Health NetworkThe National Women's Health Network is a non-profit women's health advocacy organization located in Washington, D.C.. It was founded in 1975 by Barbara Seaman, Alice Wolfson, Belita Cowan, Mary Howell, M.D., and Phyllis Chesler, Ph.D. The stated mission of the organization is to give women a...
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