What is Duavive - conjugated estrogen, bazedoxifene?
Duavive is a medicine used to treat symptoms (including hot flushes) caused by low blood levels of the female estrogen sex hormone in women who have passed menopause. It is used in patients who still have uterus and who cannot be treated with progestin-containing medicines (medicines derived from the hormone called progesterone). Duavive contains two active ingredients: conjugated estrogens and bazedoxifene .
How is Duavive used - conjugated estrogens, bazedoxifene?
Duavive can only be obtained with a prescription. It is available as modified-release tablets (containing 0.45 mg of conjugated estrogen and 20 mg of bazedoxifene), which release bazedoxifene immediately and conjugated estrogens over a longer period of time. The recommended dose of Duavive is one tablet once a day. Treatment should be continued for the shortest duration possible as long as the benefits outweigh the risks.
How does Duavive work - conjugated estrogens, bazedoxifene?
One of the active ingredients of Duavive, conjugated estrogens, acts as a hormone replacement therapy. It replaces estrogen hormones that are no longer produced naturally in women who have passed menopause, thereby alleviating symptoms such as hot flashes. However, if used alone, estrogens can cause endometrial hyperplasia (growth), which can lead to endometrial cancer. Therefore Duavive also contains the active ingredient bazedoxifene, which blocks the effects of estrogen on the uterus thereby reducing the risk of endometrial cancer. Both active substances have been available in the European Union (EU) for several years. Conjugated estrogens have been available for many years as hormone replacement therapy, while bazedoxifene was authorized in 2009 for the treatment of osteoporosis (a disease that makes bones fragile) in women who have passed menopause.
What benefit has Duavive shown - conjugated estrogens, bazedoxifene during the studies?
Duavive has been compared with placebo (a dummy treatment) in two main studies involving 996 women who passed menopause to examine their effects on hot flushes or vulvovaginal atrophy (dryness, irritation and pain around the genital area) . An additional study also examined the effects of Duavive on osteoporosis. In the study examining the effects on hot flushes, treatment with Duavive (estrogen conjugate 0.45 mg and bazedoxifene 20 mg) over a 12-week period reduced the average daily number of moderate and severe hot flushes by 7.6 compared to 4.9 placebo-flushed flushes. Treatment with Duavive also resulted in a greater average decrease in the daily severity score of hot flushes compared to placebo treatment: 0.9 compared to 0.3. Similar results were observed with a higher dosage of conjugated estrogens (0.625 mg) and bazedoxifene 20 mg compared to placebo. The study that examined the effects of Duavive on vulvovaginal atrophy revealed, compared to placebo, an improvement of some signs of vaginal atrophy but not of the most annoying symptoms. Since the studies carried out with a combination of higher dosages did not adequately demonstrate greater efficacy of this combination than the approved dosage of Duavive, the company withdrew the application for the aforementioned combination. One of the studies also examined the effects of Duavive on osteoporosis; however, since Duavive did not demonstrate a greater benefit than the use of the individual components, the company withdrew the authorization application for Duavive in the treatment of osteoporosis.
What is the risk associated with Duavive - conjugated estrogens, bazedoxifene?
The most common side effect of Duavive (which may affect more than 1 in 10 people) is abdominal pain (stomach ache). Some women should not use Duavive: these include patients who have had problems with venous thromboembolism (formation of blood clots in the veins) such as deep vein thrombosis, pulmonary embolism (formation of a blood clot in the lungs) and thrombosis of the vein retinal (formation of a blood clot in the vein located at the back of the eye), or patients who are at increased risk of developing such conditions. It must also not be used in women who have had a stroke or myocardial infarction. Finally, it should not be used in patients who are affected or are likely to develop or have had breast cancer or other cancers of which the estrogen-dependent component is known. Duavive is only indicated for women who have passed menopause. Therefore, it should not be used in women of childbearing age. For the full list of all side effects and restrictions with Duavive, see the package leaflet.
Why has Duavive been approved - conjugated estrogens, bazedoxifene?
The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Duavive's benefits are greater than its risks and recommended that it be approved for use in the EU. Duavive has been shown to improve symptoms caused by a lack of estrogen in post-menopausal women compared to placebo. Since the observed therapeutic effects were lower than the effects detected with alternative therapies (progestin-based therapies), the CHMP concluded that the use of Duavive should be limited to patients who cannot take such alternative medicines. With regard to safety, the long-term risk of endometrial hyperplasia has not been fully examined and the CHMP has recommended further studies. The CHMP also noted that the use of Duavive in the long term is associated with a risk of stroke and venous thromboembolism similar to the risk observed with the intake of conjugated estrogen and bazedoxifene alone.
What measures are being taken to ensure the safe and effective use of Duavive - conjugated estrogens, bazedoxifene?
A risk management plan has been developed to ensure that Duavive is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Duavive, including the appropriate precautions to be followed by healthcare professionals and patients. Further information is available in the summary of the risk management plan.
Other information on Duavive - conjugated estrogens, bazedoxifene
On 16 December 2014, the European Commission issued a marketing authorization for Duavive, valid throughout the European Union. For the full version of EPAR and the summary of the Duavive risk management plan, consult the website of the Agency: ema.Europa.eu/Find medicine / Human medicines / European public assessment reports. For more information about treatment with Duavive, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist. Last update of this summary: 12-2014.
