ABSTRACT
Introduction
Invasive fungal infections (IFIs) are associated with a high morbidity and mortality and their incidence is rising. Posaconazole is a triazole antifungal drug that has an important place in the prophylaxis and salvage treatment of these infections.
Areas covered
This review focuses on the efficacy, safety, pharmacokinetics, pharmacodynamics, and drug-drug interactions of posaconazole. Literature search was conducted in PubMed.
Expert opinion
Posaconazole has a broad antifungal spectrum for both yeasts and molds, with a manageable safety profile. Its efficacy for IFIs is shown in both prophylaxis and salvage treatment. This drug is available as a suspension, tablet, and solution for intravenous administration. The suspension is associated with an erratic absorption, but this is (largely) overcome with the new formulations. Posaconazole is a CYP3A4 inhibitor and substrate for UGT1A4 and P-gp so drug–drug interactions can occur. The exposure in certain subgroups needs to be studied further and the place of routine therapeutic drug monitoring is still to be established.
Article Highlights
Posaconazole is a triazole antifungal drug used for prophylaxis and salvage treatment of invasive fungal infections.
This drug is available as a suspension, tablet and solution for intravenous administration.
The suspension is associated with an erratic absorption, but this is (largely) overcome with the new formulations.
Drug-drug interactions with posaconazole can occur since it is a CYP3A4 inhibitor and substrate for UGT1A4 and P-gp.
A relationship between posaconazole exposure and treatment outcome has been shown and lower limit targets for efficacy were determined. No clear correlation between posaconazole exposure and toxicity has been detected.
Posaconazole is generally well tolerated. Frequent adverse events are gastro-intestinal and hepatic AEs, rash and pyrexia.
Declaration of interest
R. Van Daele has received travel support from Pflzer, lnc. and Gilead Sciences. I. Spriet has served as a consultant to and has received unrestricted travel and research grants from Gilead Sciences, Merck Sharpe and Dohme Corp., and Pfizer, mc and Cidara. All contracts were through and invoiced by UZ and KU Leuven. J. Maertens has served as consultant to Gilead, MSD, Pfizer, Astellas, Basilea, F2G, Cidara, Amplyx, Scynexis, Vical, Bio-Rad, Fujisawa Healthcare lnc., Zeneus (Cephalon), Viropharma, Boehringer-Ingelheim, Amgen, Celgene and Shire/Takeda; has received speakers’ fees from Gilead, MSD, Pfizer, Basilea, Bio-Rad, Fujisawa l-Iealthcare, Astellas Pharma and Zeneus (Cephalon); and has received research funding from Bio-Rad, MSD, Gilead and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.