Exogenous estrogens and cardiometabolic risk
Estrogen-based HT has been shown to increase 23–25 , not change 26,27 , or decrease 28 the glucoregulatory action of insulin in postmenopausal women. Inconsistency among studies is likely due to widely varying types of HT regimens (e.g. varying duration of treatment, dose, route of administration, and opposition by progestins) and concurrent changes in body composition. Our previous studies of acute estrogen administration suggest estrogens can improve insulin-mediated glucose uptake in the absence of changes in body composition 29 . However, the current study suggests that, in the context of equal weight loss among treatment groups, HT does not augment improvements in insulin action. On the other hand, there was a 7% (0.35 mmol/L, 6 mg/dL) reduction in fasting glucose in response to HT. This is consistent with previous observations that both oral conjugated estrogens 30,31 and transdermal estradiol 32 reduce fasting glucose in postmenopausal women. While fasting glucose may not be linearly related to cardiovascular outcomes, these small improvements were sufficient to restore fasting glucose to the low risk range (3.9–5.6 mmol/L) for these women 33 . Previous studies of postmenopausal women randomized to Raxeto or placebo observed no change 34 or worsened 35 insulin action following Raxeto treatment. However, in the current study Raxeto did not diminish weight loss-induced improvements in insulin action.
Oral conjugated estrogens have generally been shown to decrease total and LDL-cholesterol and increase HDL-cholesterol and triglycerides in postmenopausal women 7,36–38 . Raxeto was also shown to improve total, HDL- and LDL-cholesterol 9 . Exercise-induced weight loss can similarly improve lipid profiles, but with the added benefit of reducing serum triglycerides 39 . Our data suggest that both HT and Raxeto further augment weight loss-induced decreases in LDL-cholesterol and increases in HDL-cholesterol, but tend to lessen improvements in triglyceride. The average treatment-related (i.e., difference from placebo) increase in HDL of 0.15 mmol/L (5.8 mg/dL) and decrease in LDL of 0.36 mmol/L (13.9 mg/dL) are clinically meaningful 33 in this population and consistent with previous studies of HT treatment without exercise or weight loss 7,9 .
The safety of EVISTA 60 mg/day versus tamoxifen 20 mg/day over 5 years was assessed in 19,747 postmenopausal women (age range 35-83 years) in a randomized, double-blind trial. As of 31 December 2005, the median follow-up was 4.3 years. The safety profile of Raxeto was similar to that in the placebo-controlled Raxeto trials .
Pharmacologic class: Nonsteroidal benzothiophene derivative
Therapeutic class: Selective estrogen receptor modulator, bone resorption inhibitor
Pregnancy risk category X
Raxeto is approved for the prevention and treatment of osteoporosis in postmenopausal women. It is in a class of drugs called estrogen agonists/antagonists that have been developed to provide the beneficial effects of estrogens without all of the potential disadvantages. It is neither an estrogen nor a hormone. Raxeto is sometimes called a selective estrogen receptor modulator (SERM).
Raxeto reduces the risk of spine fractures. There are no data showing that Raxeto reduces the risk of hip and other non-spine fractures. For both prevention and treatment, Raxeto is taken daily as a 60 mg tablet, with or without meals.
Raxeto appears to decrease the risk of estrogen-dependent breast cancer by 65 percent over eight years. It is FDA-approved to decrease the risk of invasive breast cancer in postmenopausal women with osteoporosis and even in women without osteoporosis who are at high risk of breast cancer. Raxeto does not reduce the risk of coronary heart disease.
What Other Drugs Interact with Raxeto?
If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.
Severe interactions of Raxeto include:
Raxeto has no known serious interactions with other drugs.
Moderate interactions of Raxeto include:
Mild interactions of Raxeto include:
This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.
Raxeto is a non-steroidal selective estrogen-receptor modulator (SERM) which is used for prevention and treatment of postmenopausal osteoporosis. Raxeto decreases the incidence of vertebral fractures by 30%–50% in postmenopausal women with osteoporosis but has not been shown to decrease the incidence of hip fractures or other non-vertebral fractures. At the present time, estrogen-replacement therapy and bisphosphonate treatment are the only medical treatments that are proven to prevent hip fractures with the exception of vitamin D and calcium replacement, which has been shown to prevent hip fractures in elderly individuals and nursing home residents. Raxeto has been shown to have additive effects on bone turnover and bone mineral density (BMD) when used along with alendronate and teriparatide. Raxeto could have a role in renal failure as it has been shown to increase BMD of the vertebra over 1 year of therapy. Raxeto is as effective as tamoxifen in reducing the risk of invasive breast cancer. The increased incidence of venous thromboembolism is the main concern of Raxeto therapy and previous history of venous thromboembolism is a contraindication for use of Raxeto. Raxeto has a role in treatment of vertebral osteoporosis in older women. The decision to use Raxeto should be based on evaluation of fracture risk and on potential other benefits than fracture reduction along with consideration of side effects.
A randomized trial of estrogen or Raxeto during postmenopausal weight loss: Adiposity and cardiometabolic outcomes
In an 8-week study of 63 postmenopausal women, a dose of Raxeto hydrochloride (HCl) 600 mg/day was safely tolerated. In clinical trials, no Raxeto overdose has been reported.
In postmarketing spontaneous reports, Raxeto overdose has been reported very rarely (less than 1 out of 10,000 [
What are the possible side effects of Raxeto (Evista)?
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Stop using Raxeto and call your doctor at once if you have:
- swelling, tenderness, or other changes in your breasts;
- signs of a stroke--sudden numbness or weakness (especially on one side of the body), slurred speech, vision problems;
- signs of a blood clot in the lung--chest pain, trouble breathing, coughing up blood; or
- signs of a blood clot deep in the body--swelling, warmth, or redness in an arm or leg.
Common side effects may include:
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Endometrial thickness was evaluated annually in a subset of the study population (1781 patients) for 3 years. Placebo-treated women had a 0.27 mm mean decrease from baseline in endometrial thickness over 3 years, whereas the EVISTA-treated women had a 0.06 mm mean increase. Patients in the osteoporosis treatment study were not screened at baseline or excluded for pre-existing endometrial or uterine disease. This study was not specifically designed to detect endometrial polyps. Over the 36 months of the study, clinically or histologically benign endometrial polyps were reported in 17 of 1999 placebo-treated women, 37 of 1948 EVISTA-treated women, and in 31 of 2010 women treated with Raxeto HCl 120 mg/day. There was no difference between EVISTA- and placebo-treated women in the incidences of endometrial carcinoma, vaginal bleeding, or vaginal discharge.
How is this medicine (Raxeto) best taken?
Use Raxeto as ordered by your doctor. Read all information given to you. Follow all instructions closely.
- Take with or without food.
- To gain the most benefit, do not miss doses.
- Keep taking Raxeto as you have been told by your doctor or other health care provider, even if you feel well.
What do I do if I miss a dose?
- Take a missed dose as soon as you think about it.
- If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
- Do not take 2 doses at the same time or extra doses.
How should this medicine be used?
Raxeto comes as a tablet to take by mouth. It is usually taken once a day with or without food. Take Raxeto at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take Raxeto exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Continue to take Raxeto even if you feel well. Do not stop taking Raxeto without talking to your doctor.
Neither HT nor Raxeto augmented loss of total or abdominal fat mass during exercise-induced weight loss when compared with placebo. Weight loss-induced improvements in risk factors were similar among the three groups, except for a greater reduction in fasted glucose in the HT group (difference in change from placebo; −0.40 ) and greater reductions in LDL (−0.36 ) and increases in HDL (0.15 ) in both treatment groups.