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FK 506/fluconazole interaction enhances FK 506 nephrotoxicity
Diabete & Metabolisme
|January 1, 1994
Summary
Drug interactions between fluconazole and FK 506 can increase FK 506 levels, potentially causing kidney injury in transplant patients. Careful monitoring and dose adjustments are crucial when these medications are used together.
Area of Science:
- Pharmacology
- Nephrology
- Transplantation
Background:
- Liver transplant recipients often require immunosuppressants like FK 506 (tacrolimus).
- Diabetic patients may develop opportunistic infections, such as fungal infections, requiring antifungal treatment.
- FK 506 is metabolized by the cytochrome P450 enzyme system.
Observation:
- A diabetic liver transplant recipient on FK 506 developed severe digestive moniliasis.
- Treatment with fluconazole, an imidazole antifungal, led to a rapid increase in serum creatinine.
- FK 506 plasma concentrations (AUC and trough levels) were significantly elevated during co-administration with fluconazole.
Findings:
- Imidazole antifungals, like fluconazole, inhibit cytochrome P450 enzymes.
- This inhibition reduces the catabolism of FK 506, leading to higher drug levels.
- The observed rise in creatinine was attributed to FK 506 toxicity, resolving upon drug cessation.
Implications:
- Concomitant use of imidazole antifungals and FK 506 necessitates meticulous monitoring of FK 506 trough levels.
- Dosage adjustments of FK 506 are mandatory to prevent toxicity when these agents are co-administered.
- This interaction principle also applies to cyclosporine A in diabetic patients receiving cyclosporine.