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Low-dose fluconazole therapy potentiates the hypoprothrombinemic response of warfarin sodium
L L Crussell-Porter1, J P Rindone, M A Ford
1Pharmacy Service, Veterans Affairs Medical Center, Mountain Home, Tenn.
Background:
Fluconazole has been reported to interact with many medications. This study examined the effect of low-dose fluconazole therapy on the hypoprothrombinemic response of warfarin sodium in patients.
Methods:
Patients receiving low-intensity anticoagulation therapy with warfarin were recruited. All patients were taking stable doses of warfarin and had two baseline prothrombin times (PTs) within 10% of each other. Each patient received 100 mg of fluconazole daily for 7 days. Prothrombin times were measured on days 2, 5, and 8 during fluconazole administration.
Results:
All patients had a progressive increase in PTs. Mean (+/- SD) of PTs increased from 15.8 +/- 1 seconds before the administration of fluconazole to 18.9 +/- 1.9 seconds on day 5 and 21.9 +/- 2.2 seconds on day 8. Fluconazole therapy was stopped early in the three patients due to high PTs. The largest change in PT was 9.7 seconds. No bleeding was noted during the study.
Conclusion:
Fluconazole predictably potentiates the hypoprothrombinemic response of warfarin. Prothrombin times must be monitored when fluconazole is administered to patients taking warfarin.
Insights
Low-dose fluconazole significantly increases warfarin
Area of Science:
- Pharmacology
- Drug Interactions
- Clinical Pharmacy
Background:
- Fluconazole is known to interact with various medications.
- Limited data exists on fluconazole's effect on warfarin's hypoprothrombinemic response.
Purpose of the Study:
- To investigate the impact of low-dose fluconazole on warfarin's hypoprothrombinemic effect.
- To assess the clinical significance of this drug interaction.
Main Methods:
- Prospective study involving patients on stable warfarin therapy.
- Administration of 100 mg fluconazole daily for 7 days.
- Monitoring of prothrombin times (PTs) on days 2, 5, and 8.
Main Results:
- A progressive increase in PTs was observed in all patients.
- Mean PT increased from 15.8 to 21.9 seconds by day 8.
- Three patients discontinued fluconazole due to elevated PTs; no bleeding occurred.
Conclusions:
- Fluconazole predictably potentiates warfarin's hypoprothrombinemic effect.
- Close prothrombin time monitoring is essential when co-administering fluconazole and warfarin.