EMA’s safety committee (PRAC) has confirmed its recommendation to limit 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 follows a re-examination of its recommendation of October 2019 which was requested by one of the companies that market high-strength estradiol cream.
The PRAC reviewed available data on the safety and effectiveness of high-strength estradiol-containing creams used to treat symptoms of vaginal atrophy in women who have been through menopause. Data on these creams show that in postmenopausal women who use them, 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 addition, there are limited safety data on long term use of high-strength estradiol creams. For these reasons, the PRAC recommended that these creams should only be used for a single treatment period of a maximum of 4 weeks.
The PRAC recommends that 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.