Itraconazole prophylaxis in lung transplant recipients receiving tacrolimus (FK 506): efficacy and drug interaction.
BACKGROUND
Itraconazole is often given for fungal prophylaxis to lung transplant recipients after transplantation. The aim of this study was to determine the extent of interaction between tacrolimus and itraconazole in lung transplant recipients and the efficacy of itraconazole prophylaxis.


METHODS
The study group included 40 lung transplant recipients followed for at least 12 months. All received prophylactic itraconazole, 200 mg twice a day, for the first 6 months after transplantation. Tacrolimus levels and dosage requirements were compared during and after itraconazole therapy. Rejection rate, fungal infection rate, and renal function were assessed. The mean cost per daily treatment of the itraconazole/tacrolimus combination and tacrolimus alone was calculated.


RESULTS
The mean tacrolimus dose during itraconazole treatment was 3.26 +/- 2.1 mg/day compared with 5.74 +/- 2.9 mg/day after itraconazole was stopped (p < 0.0001) for a mean total daily dose elevation of tacrolimus of 76%. When the cost of itraconazole was taken into account, the average total daily cost of the combined treatment was US5.86 dollars less than the treatment with tacrolimus alone. No differences in the rejection or fungal infection rate, or in renal toxicity, were observed between the periods with and without itraconazole treatment, although less positive fungal isolates were identified during itraconazole therapy.


CONCLUSIONS
Prophylaxis therapy with itraconazole is highly effective. Itraconazole reduces the dose of tacrolimus and therefore lowers the cost of therapy without causing an increase in rejection rate and with renal function preservation.
Shitrit
David
D
Pulmonary Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
Ollech
Jacob E
JE
Ollech
Ayelet
A
Bakal
Ilana
I
Saute
Milton
M
Sahar
Gideon
G
Kramer
Mordechai R
MR
D000935:Antifungal Agents / Q000191:economics / Q000627:therapeutic use*; D016527:Drug Costs; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017964:Itraconazole / Q000191:economics / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D016040:Lung Transplantation; D009181:Mycoses / Q000517:prevention & control*; D011183:Postoperative Complications / Q000517:prevention & control; D016559:Tacrolimus / Q000008:administration & dosage / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D017964:Itraconazole; D016559:Tacrolimus