Pharmacological management of antifungal agents in pulmonary aspergillosis: an updated review

ABSTRACT

Introduction

Aspergillus may cause different types of lung infections: invasive, chronic pulmonary or allergic bronchopulmonary aspergillosis. Pharmacological management with antifungals poses as a challenge. Patients diagnosed with pulmonary aspergillosis are complex, as well as the problems associated with antifungal agents.

Areas covered

This article reviews the pharmacology of antifungal agents in development and currently used to treat pulmonary aspergillosis, including the mechanisms of action, pharmacokinetics, pharmacodynamics, dosing, therapeutic drug monitoring and safety. Recommendations to manage situations that arise in daily clinical practice are provided. A literature search of PubMed was conducted on November 15^th, 2020 and updated on March 30^th, 2021.

Expert opinion

Recent and relevant developments in the treatment of pulmonary aspergillosis have taken place. Novel antifungals with new mechanisms of action that extend antifungal spectrum and improve pharmacokinetic-related aspects, drug-drug interactions and safety are under current study. For those antifungals already marketed, new data related to pharmacokinetics, pharmacodynamics, dose adjustments in special situations, therapeutic drug monitoring and safety are available. To maximize efficacy and reduce the risk of associated toxicities, it is essential to choose the most appropriate antifungal; optimize its dose, interval, route of administration and length of treatment; and prevent side effects.

KEYWORDS:

• Allergic bronchopulmonary aspergillosis
• antifungals
• Aspergillus
• chronic pulmonary aspergillosis
• invasive aspergillosis
• isavuconazole
• liposomal amphotericin B
• pharmacology
• posaconazole
• voriconazole

Acknowledgments

Authors would like to thank María Pilar Navarrete Rouco and José Navarrete Rouco for their thoughtful revision of the manuscript. We would also like to thank Anthony Armenta for providing medical editing assistance for the article at hand.

Article highlights

• Patients with different forms of pulmonary aspergillosis present with special characteristics (advanced age, immunosuppression, organ impairment, hypoalbuminemia, underweight/obesity, polypharmacy, drug-drug interactions or intolerance).

• Available antifungal agents pose several limitations, rendering pharmacological management a challenge.

• Novel antifungals are under development. These drugs provide new mechanisms of action, broaden the spectrum, including azole-resistant strains and cryptic species, and improve pharmacokinetic-related aspects, drug-drug interaction profiles and safety of available agents.

• Data on the pharmacokinetics (including drug-drug interactions), pharmacodynamics, dosing, therapeutic drug monitoring and safety are up to date on current agents available, including management recommendations for situations that arise in daily clinical practice.

Declaration of interest

The authors have no 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.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was not funded.