The effect of ethinylestradiol-containing contraceptives on the serum concentration of olanzapine and N-desmethyl olanzapine

center dot Olanzapine is metabolized via CYP1A2, which is inhibited by ethinylestradiol-containing contraceptives (ECC). WHAT THIS PAPER ADDS center dot A lower serum concentration of the metabolite N-desmethyl olanzapine during co-administration of ECC confirms a CYP1A2-inhibitory action of ethinyl estradiol. center dot The CYP1A2-inhibitory action of ethinylestradiol does not provide a clinically relevant change in serum concentrations of unmetabolized olanzapine. center dot Concurrent use of ECC is not expected to increase the side effect risk of olanzapine AIM To investigate the potential interaction between olanzapine, a CYP1A2 substrate, and ethinylestradiol-containing contraceptives (ECC). METHODS The study was carried out at a routine therapeutic drug monitoring service. To identify patients who were co-administered ECC or other contraceptives, a questionnaire was sent to the physician who ordered serum monitoring of olanzapine for women aged 18-40 years during an 18 month period. The physicians were asked to provide information about contraceptive use and smoking habits. When questionnaires were returned by the physicians, the respective serum concentration data were included in the analysis. Patients were stratified into users of ECC, progestogen-based contraceptives (PBC) or no contraceptives. Dose-adjusted serum concentrations of olanzapine and the metabolite N-desmethyl olanzapine were compared between the subgroups. RESULTS A total of 149 patients were included in the study (10 ECC users and 10 PBC users). In users of ECC, we found no differences in serum concentrations of olanzapine, but significantly lower concentrations of the CYP1A2-mediated metabolite N-desmethyl olanzapine compared with users of PBC (P = 0.019) and non-contraceptive users (P = 0.012). CONCLUSION The present study confirms that ECC exhibit CYP1A2-inhibitory properties in terms of significantly lower exposure of N-desmethyl olanzapine. However, the inhibition does not provide clinically relevant changes in serum concentrations of olanzapine.