Article date: April 2008
By: Emma Andrews, Bharat D. Damle, Annie Fang, Grover Foster, Penelope Crownover, Robert LaBadie, Paul Glue, in Volume 65, Issue 4, pages 531-539
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
AIM
To assess the two‐way pharmacokinetic interaction between voriconazole and Ortho‐Novum® 1/35, an oral contraceptive containing norethindrone 1 mg and ethinyl oestradiol 35 μg.
METHODS
In this open‐label, three‐period, fixed‐sequence study, 16 healthy females received voriconazole (400 mg q12 h, day 1; 200 mg q12 h, days 2–4) (period 1), oral contraceptive (q24 h, days 12–32) (period 2), and combination voriconazole (400 mg q12 h, day 57; 200 mg q12 h, days 58–60) and oral contraceptive (q24 h, days 40–60) (period 3).
RESULTS
Voriconazole geometric mean AUCτ and Cmax increased 46% (12 682–18 495 ng h ml−1; 90% confidence interval [CI] 32, 61) and 14% (2485–2840 ng ml−1; 90% CI 3, 27), respectively, when co‐administered with oral contraceptive vs. voriconazole alone. Ethinyl oestradiol geometric mean AUCτ and Cmax increased 61% (1031–1657 ng h ml−1; 90% CI 50, 72) and 36% (119–161 ng ml−1; 90% CI 28, 45), respectively, and norethindrone geometric mean AUCτ and Cmax increased 53% (116–177 ng h ml−1; 90% CI 44, 64) and 15% (18–20 ng ml−1; 90% CI 3, 28), respectively, during voriconazole co‐administration vs. oral contraceptive alone. Neither ethinyl oestradiol nor norethindrone levels were reduced in subjects following voriconazole co‐administration. Adverse events (AEs) were generally mild, occurring less in subjects receiving voriconazole alone (36 events) vs. oral contraceptive alone (88 events) or combination treatment (68 events); four subjects experienced a severe AE.
CONCLUSIONS
Co‐administration of voriconazole and oral contraceptive increased systemic exposures of all analytes relative to respective monotherapy. Although generally safe and well tolerated, it is recommended that patients receiving co‐administered voriconazole and oral contraceptive be monitored for development of AEs commonly associated with these medications.
DOI: 10.1111/j.1365-2125.2007.03084.x
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