Efficacy of generic forms of itraconazole capsule in treating subjects with chronic pulmonary aspergillosis.

Background: Itraconazole capsules have variable and unpredictable bioavailability.
Objective: Whether the generic brands are as effective as the innovator itraconazole in treating subjects with chronic pulmonary aspergillosis (CPA) remains unclear.
Methods: In this retrospective study, we treated CPA subjects with 6-month itraconazole capsule and measured itraconazole levels at 2 weeks, 3 months and 6 months. Our primary outcome was to compare the proportion of subjects achieving therapeutic drug levels (≥0.5 mg/L) with the generic and the innovator itraconazole after 2 weeks. We performed a multivariate logistic regression analysis to ascertain whether trough itraconazole levels affected treatment outcomes. We categorised treatment response as favourable or unfavourable based on improvement (or worsening) in clinical symptoms, microbiology and imaging. We also performed morphometric analysis of different brands of itraconazole by video-dermoscopy.
Results: We included 193 (generic brands [n = 94] and innovator itraconazole [n = 99]) CPA subjects. A higher proportion of subjects achieved therapeutic levels at 2 weeks with the innovator than with the generic brands (72/99 [73%] vs. 27/94 [29%], p < .0001). The median trough level at 2 weeks was higher with the innovator than the generic brands (0.8 vs. 0 mg/L). The mean trough itraconazole levels achieved (average of three values measured over 6 months) independently predicted a favourable treatment response after adjusting for age, gender and CPA severity. On morphometric analysis, the generic brands had variable pellet numbers and sizes, and dummy pellets.
Conclusion: At 2 weeks, a significantly higher proportion of CPA subjects achieved therapeutic drug levels with the innovator than the generic itraconazole. The mean serum itraconazole levels independently predicted a favourable treatment response in CPA.
(© 2023 Wiley-VCH GmbH.)