C300 - Challenges with Voriconazole Prophylaxis for Lung Transplant Recipients

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Author Block: N. Pettit, E. Bell, D. Friedman, L. Potter, University of Chicago Medicine, Chicago, IL
*Purpose: Antifungal prophylaxis following lung transplant is recommended in the post-transplant period for up to 6 months for those where universal prophylaxis is employed. In March 2025, our transplant center changed our preferred regimen from itraconazole x6 months with amphotericin nebulization x1 month to voriconazole x6 months with amphotericin nebulization x1 month. We sought to describe challenges encountered in the first 7 months of this protocol change.
*Methods: A list of all lung and heart/lung transplant recipients was reviewed. Only patients that received voriconazole prophylaxis were included. Patients received a dosage of 200 mg every 12 hours initially with serum concentration monitoring to obtain a goal trough of 1.5 to 5.0 mcg/mL. We evaluated the following information: Number of patients transitioned to alternative antifungal prophylaxis from voriconazole, the reason for changing from voriconazole prophylaxis, alternative antifungal transitioned to, number of dosage adjustments needed to be within the goal range, and the voriconazole dosage needed to be within goal. Our CMV prophylaxis strategy is ganciclovir or valganciclovir, transitioned to letermovir after 2 weeks or at time of discharge. Letermovir is known to reduce voriconazole levels likely through CYP induction.
*Results: Eighteen patients received voriconazole prophylaxis following lung transplant. Eight (44%) of these patients were changed to other antifungal agents. Reasons for change and alternative agents are summarized in Table 1. For patients that remained on voriconazole to reach the goal trough concentration, the average number of dose adjustments was 1 (range: 0-4), and the average total daily dose to achieve a level within goal range was 550 mg.
*Conclusions: Forty-four percent of patients initiated on voriconazole prophylaxis were transitioned to an alternative antifungal due to toxicities (neurologic, hepatic, Qtc prolongation) and a potential drug-interaction. Not all reported toxicities used as a reason to change were clearly due to voriconazole, but generally presented reasonable scenarios in which a change in antifungal was warranted. Continued monitoring of toxicities and challenges with voriconazole prophylaxis at our medical center will be needed to determine if a reassessment of our antifungal prophylaxis protocol is required.

Reasons for antifungal change and alternative agents selected

Reason for change	Alternative antifungal	Voriconazole dose and day from voriconazole start	Level at time of change (mcg/mL)	Assessment of reason for change
Hallucinations (flashing lights)	Posaconazole	200 mg q12 hours; Day 14	3.6	Likely voriconazole
Drug-interaction with amiodarone	Isavuconazole	200 mg q12 hours; Day 112	6.0	Not absolute contraindication could have continued with monitoring per hospital protocol
Increased LFTs (2 cases)	Case 1: Isavuconazole Case 2: Posaconazole	Case 1: 200 mg q12 hours; Day 63 Case 2: 200 mg q12 hours; Day 85	Case 1: 1.1 Case 2: 1.2	Case 1: Unclear if voriconazole, LFTs continued to increase post-DC and remain elevated Case 2: Likely voriconazole
Confusion, somnolence, tremors/muscle spasms	Posaconazole	500 mg q12 hours; Day 66	0.2	Likely voriconazole
QTc prolongation	Isavuconazole	200 mg q12 hours; Day 105	1.5	Unclear if voriconazole alone causing this, Qtc remains prolonged off voriconazole
Possible periostitis	Isavuconazole	200 mg q12 hours; Day 16	1.2	Unlikely voriconazole, rare adverse event, usually occurs with prolonged use. Based on difficult to control post-op pain.
Hallucinations	Posaconazole	200 mg q12 hours; Day 14	0.7	Likely voriconazole