Clinical experience with itraconazole prophylaxis in paediatric liver transplant recipients: drug interaction and tolerability

Prashant Bachina1, Anil Dhawan2, Rachel Taylor2 & Anita Verma2

Author address: 

1Paediatric Liver Centre, 2Dept of Medical Microbiology, King’s College Hospital, NHS Foundation Trust, London SE5 9RS

Abstract: 

Background The reported incidence of fungal infections (FI) in liver transplant recipients (LTR) is 2-42% and aspergillosis is 1.5%-6.5% with mortality of 80%. Building works could increase the risk of Aspergillus infections. Aims To determine the extent of interaction between tacrolimus and itraconazole and its tolerability and efficacy to prevent FI including aspergillosis in PLTR. Methods 49 patients had LT and received itraconazole prophylaxis 2.5 mg/kg BD for 14 days, between 1st August 2004 and 31st December 2005 because of major building work around the paediatric liver wards. We reviewed the notes retrospectively and followed them for 100 days after LT and looked into tacrolimus levels and dosage requirements during and after itraconazole therapy. Also looked for itraconazole levels, rejection rate, liver and renal function tests, fungal infection rate and any other side effects of itraconazole. Results The median duration of itraconazole was 14 days ( range 2-62 days). The median tacrolimus level was 9.3 microgm/L while on and 6.6 mg/L while off itraconazole. Itraconazole levels were done on day 7 for 10 patients, the median level was 0.1mg/ml (range 0.00-0.24). The tacrolimus levels doubled in the patients when the itraconazole level was >0.2 mg/ml. The percentage reduction of tacrolimus dose was 45 %. while on itraconazole. The rejection rates while on itraconazole were 40%, and 60% while off itraconazole. The renal function were raised while on itraconazole There was no difference in the colonisation rate of Candida spp before and after LT, but in 3 (6.1%) patients were colonised with Aspergillus spp after LT. Itraconazole was changed to other antifungal in 8 of the 49 patients (16.3%) because of proven FI in 3 and probable FI in 5 patients. FI rate was higher 16.3% vs 10% compared to our previous group. One patient had Aspergillus infection. There was no mortality because of FI during this period. There were no other documented side effects because of itraconazole per se. Conclusions Itraconazole cannot be used safely as a prophylactic antifungal, because of poor bioavailability when given orally, difficulty in predicting tacrolimus levels while on itraconazole. Prophylaxis therapy with itraconazole is less effective to prevent FI.
2007

abstract No: 

P 039

Full conference title: 

Federation of Infection Societies
    • FIS (2007)