Abstract
Mold-active azole antifungals are commonly prescribed for the prevention of invasive fungal infections in lung transplant recipients. Each agent exhibits a unique pharmacologic profile, an understanding of which is crucial for therapy selection and optimization. This article reviews pharmacologic considerations for three frequently-used azole antifungals in lung transplant recipients: voriconazole, posaconazole, and isavuconazole. Focus is drawn to analysis of drug-interactions, adverse drug reactions, pharmacokinetic considerations, and the role of therapeutic drug monitoring with special emphasis on data from the post-lung transplant population.
Highlights
The focus of this review is on pharmacologic considerations with the use of moldactive azole antifungals voriconazole, posaconazole, and isavuconazole in lung transplant recipients, given their frequency of use in this population and often extended durations
While simvastatin and atorvastatin area under the curve (AUC) increase >100% when co-administered with some azoles, empirical dose reductions of 50% with subsequent monitoring is recommended by some authors to be safe
In a study examining reasons for discontinuation of prophylactic azoles in lung transplant recipients, 54.5% of voriconazole exposure episodes resulted in early therapy discontinuation due to side effects, with LFT abnormalities listed as the cause of discontinuation in 18.1% of cases [35]
Summary
Lung transplant recipients are at substantial risk for developing invasive fungal infections (IFIs), with a reported cumulative incidence of 8.6% in the first year after transplantation. (44%), in particular Aspergillus fumigatus, and other molds (19.8%) cause the majority of IFIs in lung transplant recipients [1]. Guidelines recommend an extended duration of prophylaxis (3–6 months) when it is employed [4,5,6], and in patients who do develop invasive mold infection (IMI), therapy duration can range from 6 weeks to lifelong [5]. The focus of this review is on pharmacologic considerations with the use of moldactive azole antifungals voriconazole, posaconazole, and isavuconazole in lung transplant recipients, given their frequency of use in this population and often extended durations. Development of azole resistance in Aspergillus in lung transplant recipients is uncommon. Areas addressed include drug–drug interactions, short- and long- term toxicities, and the role of therapeutic drug monitoring
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