a-t 2015; 46: 113

Emergency contraception - hormonal contraceptives can reduce the efficacy of ulipristal (ELLAONE): The US prescribing information for the emergency contraceptive ulipristal (ELLAONE; a-t 2015; 46: 1-2 and 30-1, 2013; 44: 21-2) now carries a warning, according to which hormonal contraceptive agents should be used no sooner than five days after taking the progesterone receptor modulator. This has been prompted by indications of decreased efficacy of ulipristal caused by the progestogen component of the contraceptives, an effect which has been attributed to competition at the site of the progesterone receptor (1,2). In the clinical studies of ulipristal, only women who had not previously used hormonal contraception and continued not to do so until the end of the study were allowed to take part (3-5). It has not yet been investigated whether ulipristal also prevents pregnancy if regular hormonal contraception is continued or commenced after the pill is taken. According to a recently published randomised, placebo-controlled crossover comparison, however, intake of a desogestrel minipill (CERAZETTE, generics) commencing the day after use of the emergency contraceptive markedly reduces the ovulation-inhibiting effect of ulipristal: within five days after the use of emergency contraception, ovulation occurred in 13 of 29 cycles with desogestrel, but in only 1 of 29 cycles with placebo (45% versus 3%, p = 0.0054) (6). A further study originally designed to investigate the effect of ulipristal on the contraceptive activity of a combined oral contraceptive pill containing ethinyl estradiol and levonorgestrel (MICROGYNON, among others) (7) also raises suspicion of a decrease in the efficacy of the progesterone receptor modulator (2). Taking into account the data from both of these studies, a post hoc analysis also calculated for the oestrogen-progestogen combination compared with placebo a numerically greater proportion of cycles in which ovulation took place within six days after taking ulipristal (26% vs. 10%, p = 0.15) (2). While the supplier, HRA Pharma, has assumed impaired efficacy of ulipristal caused by progestogen-containing contraceptives on the basis of these data and has thus deemed necessary a five-day interval prior to the use of hormonal contraception in the USA (2), according to the company no corresponding change is planned in Germany or Europe. According to the company, the results of both studies were presented in detail to the EMA and found to be insufficient to warrant a warning notice in the prescribing information regarding a five-day pause (8). In the European Summary of Product Characteristics (SPC), therefore, the word "immediately" has simply been deleted (8), such that it now says that "if a women wishes to start or continue using hormonal contraception, she can do so after using ELLAONE" (9) - a formulation which in our opinion is not only insufficient but also thoroughly misleading, -Ed.