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.