*Purpose: We hypothesized that crushed posaconazole delayed release (POSA DR) tablets can reach therapeutic levels in lung transplant recipients who are at risk for invasive aspergillus and are unable to swallow due to intubation or dysphagia.

*Methods: This was a retrospective study including adult lung transplant recipients, transplanted at the University of California, San Francisco between January 2018 and October 2021, who received 300mg of crushed POSA DR tablets compared to a cohort who received 300mg of intact tablets for at least 5 days with troughs drawn on day 5 or later. POSA liquid solution was not used due to its erratic absorption. Critical illness, diarrhea, and breakthrough aspergillus were assessed. Chi-square tests were used for statistical analysis. Therapeutic levels were defined as POSA levels ≥0.7 mg/L for prophylaxis and ≥1.5 mg/L for treatment.

*Results: 8 subjects received crushed POSA and were compared to 33 controls. Overall, 50% of crushed subjects were therapeutic compared to 87.9% in the intact group (p=0.02). The median initial trough was 0.55 mg/L (0.2-3.4) for crushed and 1.1 mg/L (0.4-2.4) for intact. A subset analysis compared those with troughs at 5-7 days and 8-14 days. At 5-7 days, 33.3% of crushed subjects were at goal compared to 87.5% in the intact group (n= 6 and 8, respectively) (p=0.04). At 8-14 days, 100% of crushed subjects were at goal, while 88% were in the intact group (n=2 and 25, respectively) (p=0.6). Notably, a majority of subjects not at goal had diarrhea, 62.5%. All troughs were drawn appropriately. None of the crushed subjects had breakthrough aspergillus after three months.

*Conclusions: This study showed that crushed POSA is a viable option, with a few considerations. The crushed group took longer to reach therapeutic levels than the intact group, however all crushed subjects in the 8-14 day cohort reached goal. Given the critical nature of this population, the delay in reaching therapeutic levels could increase the risk of breakthrough fungal infections and a POSA loading dose should be considered. In addition, diarrhea appeared to be a significant factor in achieving therapeutic troughs and IV may be preferred while diarrhea persists. Limitations include this is a small, retrospective study with minimal serial trough levels. Future directions include loading at initiation and switching to IV in patients with diarrhea.

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