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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.
Objective:
To report the influence of rifampin coadministration on the pharmacokinetics of fluconazole in 2 critically ill patients.
Case Summaries:
The pharmacokinetics of fluconazole are reported in 5 patients in the intensive care unit (ICU), 2 of whom received rifampin and 3 who received only fluconazole. Patient 1 was a 52 year-old man with bilateral pneumonia who received rifampin for 9 days in addition to other antibiotics when fluconazole was added for suspected fungal superinfection. Patient 2, a 39-year-old man with steroid-dependent asthma was admitted to the ICU with a right middle lobe pneumonia and ventilatory insufficiency. Because of rapid clinical deterioration, intravenous rifampin 600 mg q12h and fluconazole 100 mg q24h were added to conventional antibacterial therapy. Patients 3-5 received intravenous fluconazole therapy, but were never administered rifampin prior to their antifungal therapy.
Discussion:
Fluconazole has gained wide use as an antifungal agent because of its efficacy, limited toxicity, and the paucity of reported drug interactions. In some clinical situations, however, the drug must be coadministered with rifampin. Limited data in healthy volunteers suggest that the coadministration of rifampin and fluconazole results in a 23% reduction in the fluconazole area under the concentration-time curve (AUC). In this report, we found a statistically significant lowering of the AUC (52%) and a 93% higher total body clearance of fluconazole in patients treated with rifampin.
Conclusions:
Although limited data are available describing the magnitude of the interaction between fluconazole and rifampin in patients, our data suggest a more significant interaction than previously reported. If the concurrent administration of the 2 drugs in unavoidable, the patient's clinical response to treatment should be monitored closely, as the unexpectedly large reduction in fluconazole serum concentrations may lead to poor treatment outcomes.
Insights
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.