Objective: This open-label, two-period, crossover study was conducted to evaluate the effect of a single 150 mg dose of fluconazole on the pharmacokinetics of ethinyl estradiol in healthy female subjects.
Study design: Ten subjects regularly taking Ortho-Novum 7/7/7 (Ortho Pharmaceutical, Raritan, N.J.) and 10 subjects regularly taking Triphasil (Wyeth-Ayerst Laboratories, Philadelphia), which contain ethinyl estradiol 35 microg and 30 microg during days 1 to 6, respectively, were randomly assigned to receive a single 150 mg dose of fluconazole 2 hours before the oral contraceptive, on pill day 6 of one of two menstrual cycles. Ethinyl estradiol serum concentrations were measured at baseline and up to 24 hours after oral contraceptive intake. No fluconazole was administered during the other menstrual cycle, which served as the control.
Results: Mean serum concentrations of ethinyl estradiol were increased after fluconazole administration in both oral contraceptive groups. Maximum observed serum concentration and area under the concentration-time curve values were significantly (p < 0.05) greater during the fluconazole regimens (vs regimens without fluconazole) for both oral contraceptive groups and for combined values of the two oral contraceptive groups. The mean time to reach the maximum concentration was not altered by concomitant fluconazole administration.
Conclusions: These findings suggest that there is a potential for a clinically significant interaction between coadministration of fluconazole and ethinyl estradiol in oral contraceptives.
PIP: The effect of a single dose of the imidazole antifungal agent fluconazole on circulating ethinyl estradiol levels in oral contraceptive (OC) users was investigated in an open-label, two-period, crossover study. 10 regular users of Ortho-Novum 7/7/7 and 10 women regularly taking Triphasil were randomly assigned to receive 150 mg of fluconazole 2 hours before OC ingestion on pill day 6 of one of two menstrual cycles. Mean serum concentrations of ethinyl estradiol were increased after fluconazole administration in both OC groups. Maximum observed serum concentration and area under the concentration time curve values were significantly greater during the fluconazole cycle for both OC groups and for the combined values of the two groups (p 0.05). The mean time to reach the maximum concentration was not altered by concomitant fluconazole administration. Mean serum ethinyl estradiol concentrations were greater at all time points in Ortho-Novum 7/7/7 users than Triphasil users. These findings suggest there is potential for a clinically significant drug interaction between co-administration of fluconazole and ethinyl estradiol. The most likely site of this drug interaction is the hepatic cytochrome P450 enzyme system. Since a single dose of 150 mg of fluconazole is standard treatment for common vaginal yeast infections, such concomitant therapy is likely in OC users at some point and its implications should be considered by prescribing clinicians.