Evaluation of interaction between fluconazole and an oral contraceptive inhealthy women

OBJECTIVE: To evaluate the potential pharmacokinetic interaction between 2 x 150 mg fluconazole administered once weekly and an oral contraceptive (OC ) containing ethinyl estradiol and norethindrone. METHODS: A placebo-controlled, double-masked, randomized, two-way crossover study was used to investigate the pharmacokinetic interaction between 300 mg fluconazole once weekly and the OC Ortho Novum 7/7/7 (Ortho-McNeil Pharm aceutical, Inc., Raritan, NJ) in 26 healthy women, 18-36 years old. In the first cycle (28 days), subjects received OC only. In the second cycle, subj ects were assigned randomly to receive OC-fluconazole or OC-placebo. In the third cycle, subjects were crossed over to the opposite treatment. RESULTS: Data for 21 subjects who completed the study were included in the pharmacokinetic analysis; data for all 26 subjects were included in the saf ety analysis (26 OC only; 24 OC-fluconazole; 23 OC-placebo). Treatment with OC-fluconazole resulted in small but statistically significant increases i n 0-24 hour area under the plasma concentration-time curve (AUC(0-24)) for both ethinyl estradiol (mean 24%, 95% confidence interval [CI] 18%, 31%) an d norethindrone (mean 13%, 95% CI 8%, 18%) as compared with treatment with OC-placebo. Ethinyl estradiol maximum plasma concentration (C-max) was slig htly (mean 8%, 95% CI 2%,15%) though statistically significantly higher for OC-fluconazole treatment as compared with OC-placebo treatment. Norethindr one C-max was not different (95% CI - 6%, 11%) between the two treatment gr oups. No adverse events related to treatment were seen in the fluconazole t reatment group. CONCLUSION: The concomitant administration of 300 mg fluconazole once weekl y, twice the recommended dose for vaginal candidiasis, to women using OCs r esults in a slight increase in OC concentrations. Therefore, it appears tha t there is no threat of contraceptive failure because of concomitant flucon azole administration. (C) 2001 by the American College of Obstetricians and Gynecologists.