Voriconazole to fluconazole:
Of the three cases that switched from voriconazole to fluconazole, two were changed due to suspected drug-related toxicity and the third stepped down from treatment of possible invasive fungal infection to prophylaxis (Table 1). All had Grade 3 liver injury prior to the antifungal switch with peak GGT levels, from 518 to 735 IU/L (12.9 to 18.3 times the upper limit of normal (x ULN)) and two cases had elevated ALT levels of 140 to 186 IU/L (4.1 to 5.0 x ULN). Immediately prior to triazole antifungal switch, voriconazole levels were subtherapeutic in one patient (Case 1 0.34 mg/L one week prior) and within target range in two others (Case 2 1.48 mg/L three days prior; Case 3 2.87 mg/L five days prior). However, for Case 3, LFT abnormalities developed two weeks after a supratherapeutic level, when their voriconazole trough concentration was 5.94 mg/L. Notably, Case 3’s LFT results did not improve with initial dose reduction. Although all three cases had improvement in their LFT results with the antifungal switch, one developed LFT abnormalities on day 50 coinciding with an episode of febrile neutropenia (Case 3). Case 2 was re-challenged with voriconazole 1 week later and had recurrence of their LFT abnormalities requiring a change in treatment to an alternative antifungal, micafungin.