Single-dose fluconazole for vulvovaginal candidiasis: impact on prothrombin time in women taking warfarin.

Abstract

To estimate the effect of a single oral 150-mg dose of fluconazole on the prothrombin time of women on long-term warfarin therapy.
Women on warfarin therapy for 6 months or more with no change in dose within 4 weeks of the study, and a prothrombin time (PT) with an International Normalized Ratio (INR) between 2 and 3 were invited to participate. Two consecutive baseline PTs were obtained (days -1 and 0), and women were given 150 mg of fluconazole. Prothrombin times were measured on days 2, 5, and 8 of the study. The change in PT was calculated from the difference between the baseline PT on day 0 and the PT during the study period. To detect a 10% difference in a PT (approximately 2.1 seconds) of a patient with an INR of 2.0, at P < .05 and a power of 90%, 5 subjects are required.
Six women participated. The mean (+/- standard deviation) PT for day 0 was 27.7 +/- 4.1 seconds or INR 2.6 +/- 0.4. The PT increased 11% at day 2, 34% at day 5, and 2% at day 8; these differences were not statistically significant. However, one half of the women had either a clinically relevant increase of the INR greater than 4, or bleeding that required their dosage of warfarin to be decreased.
A single 150-mg oral dose of fluconazole may increase the PT to a clinically relevant level in a woman on chronic warfarin therapy. Clinicians should monitor the PT carefully after a single dose of fluconazole.
II-2.