EMA’s safety committee (PRAC) has recommended limiting the use of high-strength creams containing 100 micrograms/gram (0.01%) of estradiol to a single treatment period of up to 4 weeks. This measure is intended to minimise the risk of side effects caused by estradiol absorbed into the bloodstream from creams applied inside the vagina to treat symptoms of vaginal atrophy in women who have been through menopause.
The PRAC has reviewed available data on the safety and effectiveness of high-strength estradiol-containing creams, including data on the amount of estradiol in the blood. These data showed that in postmenopausal women who had used these creams, the levels of estradiol in the blood were higher than normal postmenopausal levels. The PRAC concluded that absorption of estradiol into the bloodstream is of concern and could result in similar side effects to those seen with hormone replacement therapy (HRT). The side effects of HRT taken orally or used transdermally (as patches) include venous thromboembolism (formation of blood clots in the veins), stroke, endometrial cancer (cancer of the lining of the womb) and breast cancer. In the absence of safety data for long-term use of high-strength estradiol creams, the PRAC recommended that these creams should only be used for a single treatment period of a maximum of 4 weeks.
The prescribing information for these creams will be updated with the new recommendations. A warning that the medicine is to be used for a single treatment period of up to 4 weeks only will be placed on the outer and inner packaging and the size of the tube will be limited to 25 grams to prevent use for longer than recommended.
Information for patients
- High-strength estradiol creams (100 micrograms/gram) applied inside the vagina should only be used for a single treatment period of a maximum of 4 weeks. This is because the hormone estradiol in these creams can be absorbed into the bloodstream and may increase the risk of side effects such as blood clots, strokes and certain types of cancer if these creams are used for extended periods.
- Do not use high-strength estradiol cream if you are already taking another HRT (hormone replacement therapy) medicine.
- If you have any questions about your treatment, talk to your doctor or pharmacist.
Information for healthcare professionals
- High-strength estradiol creams should not be prescribed for longer than a single treatment period of 4 weeks due to the risks associated with systemic exposure to estradiol.
- Pharmacokinetic data on high-strength estradiol creams (100 micrograms/gram) for intravaginal use show substantial systemic exposure to estradiol, with levels higher than the normal postmenopausal range (up to five times above the upper limit of the reference postmenopausal estradiol serum levels of 10–20 pg/ml).
- Systemic exposure to estradiol could be associated with side effects similar to those of oral and transdermal HRT products i.e. endometrial hyperplasia/carcinoma, breast and ovarian cancer and thromboembolic events.
- High-strength estradiol creams should not be prescribed with other HRT medicines.