Results
Over the five-year period, seven cases fulfilled the inclusion criteria. The median age was 7.3 years (range 4.2-16.6) and 6/7 were male (Table 1). Four had a hematological malignancy, two had a primary immunodeficiency and five were hematopoietic stem cell transplant recipients (HSCT) (Table 1). The most common azole switch was voriconazole to fluconazole (3/7), followed by fluconazole to voriconazole (2/7). One child each switched from voriconazole to itraconazole, and posaconazole to fluconazole.
Of the seven cases, five had Grade 3 liver injury and two had Grade 2 liver injury. All children had an elevated Gamma-glutamyl Transferase (GGT) level (Grade 2 to 3) and three had Grade 2 Alanine Aminotransferase (ALT) abnormalities (Table 1; Figure 1). These LFT abnormalities were deemed as ‘possibly’ in four cases, and ‘probably’ in three cases to be related to the first azole antifungal as per the Naranjo criteria 6. All had improvement in their LFT abnormalities after the switch to an alternative azole antifungal, however, in only two patients, did the LFTs normalise by the end of treatment (Case 3 and 4, Table 1). The most common concomitant medications include acetaminophen in all cases, penicillin/beta-lactamase inhibitors in 5 cases, antiemetics in 4 cases and chemotherapeutics in 3 cases (Table 1).