Evista (Raloxifene)

In December 22, 1997, the U.S. Food and Drug Administration (FDA) approved the drug raloxifene for the prevention of the bone-weakening disease osteoporosis. Dr. Kimberley Mulvihill, an obstetrician and gynecologist, talks about how raloxifene works and who might best benefit from its use.

Q: What is raloxifene?

A: Raloxifene (brand name Evista) is approved by the FDA for use in the prevention of osteoporosis. It belongs to a category of drugs called selective estrogen receptor modulators (SERMs), the so-called designer estrogens.

Q: How does it work?

A: Raloxifene blocks bone resorption, the process by which old bone is dissolved and eliminated. This leads to a higher level of circulating calcium and a slight increase in total bone density (1 to 2 percent). Raloxifene also lowers the blood level of total cholesterol and low-density lipoprotein cholesterol (the bad cholesterol). Unfortunately, unlike estrogen, raloxifene does not appear to increase high-density lipoprotein (the good cholesterol).

However, one of the most promising findings was that raloxifene may help decrease the incidence of breast cancer. This particular study followed women participants over a 30-month period and saw a significant reduction in the incidence of newly diagnosed breast cancer.

Q: How long is it recommended that women take it? Is it something you could or might want to stay on indefinitely?

A: To achieve the greatest benefit in protection against osteoporosis, women will need continuous, long-term treatment with raloxifene.

Q: How is the drug taken? Are there any special instructions? With meals? Standing up?

A: Raloxifene is taken once a day with no regard to meals or position. This will be a welcome change for women who have tried Fosamax, which has a fairly rigorous dosing schedule.

Q: What are the side effects and risks of raloxifene?

A: Raloxifene may precipitate hot flashes in women as treatment is started. These are generally mild and are most likely to occur in the first six months of use. Leg cramps are also reported more frequently in women taking raloxifene. Women taking raloxifene are at an increased risk of developing a deep-vein thrombosis or clots. The risk is comparable to that of women on hormone replacement therapy (HRT). Raloxifene should be discontinued 72 hours prior to and during any period of prolonged immobilization, such as a major surgical procedure.

Q: What does it cost? How will the cost compare to HRT?

A: The cost of 60 milligrams of raloxifene taken daily is about $70 per month.

Q: Who will want to take it, and why?

A: Raloxifene is an exciting new option for many women. Postmenopausal women who are not following a regimen of hormone replacement therapy will spend one-third of their lives in a hormone-deficient state. The long-term consequences of this deficiency are osteoporosis and cardiovascular disease. Osteoporosis affects more than 20 million women in the United States, and more than 50 percent of U.S. women will suffer a bone fracture related to osteoporosis. The risk of osteoporosis is greatest for postmenopausal women. Women with severe osteoporosis are susceptible to fractures with fairly ordinary activities: Even forceful coughing or stepping off a curb can be enough stress to fracture a weakened, osteoporotic bone!

HRT can prevent osteoporosis. Unfortunately, more than 80 percent of women who are prescribed HRT discontinue their medication within two years. Women stop these medications primarily over concern about their risk of breast or uterine cancer, or the development of unwanted side effects, such as vaginal bleeding, weight gain, and breast tenderness.

Raloxifene offers women the means to protect their bones against osteoporosis, without stimulating breast or uterine tissue. In this manner, they avoid any annoying vaginal bleeding, as well as any increased risk of breast or uterine cancer. They may even be able to reduce their risk of breast cancer by taking this drug.

Many women have been waiting for a medication like this. They recognize the benefits of hormonal therapy in preventing long-term consequences of estrogen depletion yet are concerned about the potential increased cancer risks. Raloxifene will let these women be proactive with their health maintenance while allaying their cancer fears.

Q: Who might not want to, and why?

A: While raloxifene prevents bone loss, it has not been proven to reverse osteoporosis that has already occurred. Therefore, a woman with osteoporosis or skeletal fractures would best be treated with a potent anti-resorptive medication, such as Fosamax.

Premenopausal women are not candidates for raloxifene. They are still producing estrogen, which naturally protects women’s bones. They should focus their energy on lifestyle changes that will help protect them. This means getting enough calcium and vitamin D, doing weight-bearing exercise, stopping smoking, and drinking alcohol only in moderation.

Women who are bothered by significant menopausal symptoms are best treated with estrogen therapy. This can safely be used in the short term and is proven to be effective. Raloxifene does not alleviate menopausal symptoms of hot flashes, insomnia, mood swings, or night sweats. In fact, some women have noticed an increase in hot flashes during the first few months of treatment with raloxifene.

Q: Are there any absolute contraindications to taking raloxifene?

A: Raloxifene is contraindicated in women who are, or may become, pregnant. Women need to be aware of the potential hazard this drug poses to any pregnancy that occurs while taking the medication. Raloxifene is excreted in breast milk and is therefore also contraindicated in nursing women. A history of venous thrombosis is, similarly, an absolute contraindication to raloxifene use.

Q: What about men?

A: The safety and efficacy of raloxifene use by men has not been studied. The possible use of raloxifene for treatment of prostate cancer or osteoporosis in men is an area of further research.

Q: Could you take both raloxifene and HRT, or do you have to choose one type of therapy?

A: It seems like this would be a perfect solution: Take a little of each and have the best of both worlds. Unfortunately, there have been no prospective, randomized clinical trials evaluating the concurrent usage of raloxifene and estrogen. This represents another area of further research. In the meantime, the concurrent use of raloxifene and estrogen is not recommended.

Q: What are the risks and drawbacks associated with taking raloxifene instead of HRT?

A: Estrogen therapy is well known to alleviate the symptoms of menopause. There is also strong evidence that estrogen will prevent osteoporosis and protect against cardiovascular disease. While raloxifene has been proven to help prevent osteoporosis, it does not alleviate menopausal symptoms, and it has not yet been proven to protect women against cardiovascular disease.

Q: What are the benefits of taking raloxifene instead of HRT?

A: The advantage of raloxifene over HRT is having bone protection without the cancer risk. A great benefit will lie in adherence to the prescribed treatment plan. Women will be more likely to take this medication because their fears about a potential increased risk of breast or uterine cancer will be removed. They will also not be bothered by unwanted vaginal bleeding or breast pain. Women who take their medication will, in turn, see the benefits in terms of improved long-term health.

Q: Will raloxifene replace HRT?

A: Raloxifene offers another alternative to women who are concerned about their long-term health. It will not replace HRT in the treatment of menopausal symptoms. Raloxifene will present an option for women who are asymptomatic and want to be proactive in maintaining the integrity of the skeletal system. Perhaps we will learn that HRT is most beneficial during the first two to five years after menopause and that raloxifene should then be substituted for long-term use. As is often the case, more research and time will tell.

Q: Are researchers studying raloxifene for other uses?

A: Yes. Researchers are investigating whether raloxifene can treat established osteoporosis and prevent cardiovascular disease in postmenopausal women. Further research should also answer the question of how raloxifene interacts with brain tissue. If it mimics estrogen in the brain, it may prove helpful in the prevention of Alzheimer’s disease.

On the other hand, some researchers have expressed concern about the woman who develops breast cancer while taking raloxifene: Could she be producing cells that are resistant to tamoxifen and thereby lose that option in her breast-cancer treatment? These, and other issues, will require further study.

Q: Can you tell us more about “designer estrogens” or SERMs?

A: These agents were designed in an attempt to produce the ideal estrogen. They are tissue-specific compounds that are intended to emphasize the positive and minimize the negative effects of estrogen. They work by binding to estrogen receptors and then, depending on the type of tissue they’re bound to, either blocking or facilitating the next step, such as cell division.

For example, the most well-known drug in this class is tamoxifen, which is used today to treat breast cancer. Tamoxifen attaches to estrogen receptors and competes with a woman’s own natural estrogen for these receptor sites. In the breast, the receptors that are occupied with tamoxifen are blocked and cancer cells are prevented from dividing. In the uterus, however, tamoxifen stimulates estrogen receptors in the endometrial lining, and this stimulation increases cell growth and the risk of uterine cancer. Raloxifene, a second-generation SERM, was designed to avoid this latter unwanted effect.

Q: What does it mean that these drugs work by imitating the effect of estrogen on some tissues, but not others?

A: Estrogen has been proven to have a beneficial effect on the bone and the heart, yet a potentially harmful effect on the breast and the uterus. This poses a dilemma for menopausal women. They want the protective effect of estrogen, but they are concerned about the risk of cancer. SERMs offer women the good without the bad. This class of drugs will provide protection for a woman’s bones and heart without increasing her risk of breast or uterine cancer.

Q: Why is there a need for this kind of drug?

A: Medical research strives to improve existing treatments and create new ones as a need arises. SERMs were developed in an attempt to find the perfect estrogen. This process is driven by concern for the health of postmenopausal women. This large, growing group of patients has special health-care needs.

Q: Are there other drugs in this class under study?

A: Many other SERMs are under development. Three SERMs (droloxifene, idoxifen, and levomeloxifene) are currently being studied in women. All four drugs are being investigated for the prevention of osteoporosis and also for the possible use in breast cancer treatment.

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