Antifungal Use and Therapeutic Monitoring of Plasma Concentrations of Itraconazole in Heart and Lung Transplantation Patients

Abstract

The prophylactic use of itraconazole has dramatically reduced the incidence of fungal infections in patients after solid-organ transplantation. To further reduce this incidence, it has been suggested that plasma concentrations of itraconazole be monitored and maintained above a putative minimum target concentration of 500 ng/mL. A retrospective audit was undertaken of patients who had had a heart or lung transplant over a 14-month period (between January 1, 2010 and March 31, 2011). The itraconazole prophylaxis regimen (dose, time of last dose, time of blood collection) and plasma concentrations were recorded together with the use of concomitant antacid medication. Details of breakthrough fungal infections were documented. Eighty-four heart or lung organ transplantations were undertaken in the study period; 57 were treated prophylactically with itraconazole. Plasma concentrations of itraconazole were monitored in 56% (n = 32) of these cases. Considerable interpatient (range, 50-2000 ng/mL) and intrapatient variability in plasma concentrations was observed. The putative target was not achieved consistently in the majority of cases. All patients were taking a proton pump inhibitor. Six of the cohort developed an invasive fungal infection. None of the 3 patients for whom plasma concentrations were monitored was above the target concentration. Further clinical studies, involving monitoring of the active metabolite and attention to the importance of the stereoisomers of itraconazole, may give better insight into the appropriateness of the currently suggested minimum target concentration, whose validity remains uncertain. Formulations with improved absorption characteristics could reduce the variability of absorption with the goal of further reducing the incidence of infrequent, but life-threatening, invasive fungal infections.