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Rifampin-fluconazole interaction in critically ill patients
D P Nicolau1, H M Crowe, C H Nightingale
1Division of Infectious Disease, Hartford Hospital, CT 06102, USA.
The Annals of Pharmacotherapy
|October 1, 1995
Summary
Rifampin significantly reduces fluconazole levels in critically ill patients, lowering the area under the curve by 52%. This interaction necessitates close patient monitoring to prevent treatment failure when coadministering these drugs.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Fluconazole is a widely used antifungal agent with a favorable safety profile and few known drug interactions.
- Coadministration of fluconazole with rifampin is sometimes clinically necessary.
- Previous studies in healthy volunteers indicated a 23% reduction in fluconazole's area under the concentration-time curve (AUC) when given with rifampin.
Observation:
- This study investigated the pharmacokinetics of fluconazole in 5 critically ill patients, including 2 who received concurrent rifampin therapy.
- Patient 1 received rifampin for 9 days alongside fluconazole for suspected fungal superinfection.
- Patient 2 received intravenous rifampin and fluconazole for pneumonia and ventilatory insufficiency.
Findings:
- Concurrent administration of rifampin resulted in a statistically significant 52% reduction in fluconazole's AUC.
- Total body clearance of fluconazole was 93% higher in patients treated with rifampin.
- This observed interaction is more pronounced than previously reported in healthy volunteers.
Implications:
- The substantial decrease in fluconazole serum concentrations due to rifampin coadministration may compromise treatment efficacy.
- Clinicians should closely monitor patient response when fluconazole and rifampin must be administered together.
- These findings highlight the importance of considering drug-drug interactions in critically ill patients to optimize therapeutic outcomes.