Evaluation of the drug-drug interaction between triazole antifungals and cystic fibrosis transmembrane conductance regulator modulators in a real-life cohort

Med Mycol. 2024 Mar 7;62(3):myae020. doi: 10.1093/mmy/myae020.

Abstract

Limited data on the clinical management of drug-drug interactions between triazoles and Cystic Fibrosis transmembrane conductance regulator (CFTR) modulators are available. We retrospectively evaluated azole target attainment and dose adaptations in patients from two Dutch CF centres concomitantly receiving triazoles and CFTR modulators. In total, 21 patients with 59 triazole trough concentrations were evaluated. Subtherapeutic concentrations were frequently observed, especially for itraconazole and voriconazole. Of the investigated antifungal agents, posaconazole appears the most preferable option. Our results emphasize the importance of adequate management of this interaction and underpin the added value of therapeutic drug monitoring of triazoles in this population.

Keywords: CF; CFTR modulators; antifungal agents; pharmacology; therapeutic drug monitoring.

Plain language summary

Fungal infections are serious complications in Cystic Fibrosis (CF) patients. We evaluated patients concomitantly receiving triazoles and CF transmembrane conductance regulator modulators: subtherapeutic triazole exposure was frequently observed. Posaconazole appears the preferable antifungal agent.

MeSH terms

  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Cystic Fibrosis Transmembrane Conductance Regulator* / genetics
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / veterinary
  • Humans
  • Mutation
  • Retrospective Studies
  • Triazoles / pharmacology
  • Triazoles / therapeutic use

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Antifungal Agents
  • Triazoles