Ethinylestradiol Fluconazole

The effect of fluconazole 150 mg on circulating ethinylestradiol concentrations has been studied on day 6 of one of two cycles in women taking oral contraceptives (343). The serum concentrations of ethinylestradiol (Cmax and AUC) were significantly increased by fluconazole, but tmax was not affected. These findings suggest that there is a potential for a clinically significant interaction between fluconazole and ethinylestradiol, by inhibition of estrogen metabolism. 

Since oral contraceptive users sometimes need to be treated for vaginal candidiasis, the question arises which of the available treatments can be used without risk of impairing contraception. In a crossover placebo-con-trolled study, fluconazole 300 mg weekly for two cycles has been studied in 21 healthy women using Ortho-Novum 7/7/7 as a contraceptive (344). Fluconazole in this dose, which is twice that ordinarily recommended, produced small but statistically significant increases in the AUCo-24 for both ethinylestradiol (mean 24% increase) and norethindrone (mean 13%). The Cmax of ethinylestradiol was slightly, but just significantly, higher... 

In another study, fluconazole reduced the systemic availability of ethinylestradiol in an oral contraceptive, but there was no information about the doses used (75). 

In an open, crossover study in 10 young healthy subjects, fluconazole 150 mg increased the serum concentrations of ethinylestradiol 30-35 pg/day (103). 

The potential pharmacokinetic interaction between fluconazole 300 mg once weekly and an oral contraceptive containing ethinylestradiol and norethindrone (Ortho Novum 7/7/7 Ortho-McNeil Pharmaceutical Inc, Raritan, NJ) has been studied in a placebo-controlled, double-blind, randomized, two-way, crossover study in 26 healthy women aged 18-36 years (104). During the first cycle they took the oral contraceptive only. During the second cycle they were assigned randomly to oral contraceptive -1- fluconazole or oral contraceptive + placebo. In the third cycle they... 

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