CASE REPORT article
Front. Pharmacol.
Sec. Translational Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1616061
This article is part of the Research TopicManaging COVID-19 in Heart and Lung Transplant Patients: Challenges and SolutionsView all 4 articles
UNEXPECTED VORICONAZOLE TOXICITY DUE TO NIRMATRELVIR/RITONAVIR: A CASE REPORT ON DRUG-DRUG INTERACTION AND THE ROLE OF THERAPEUTIC DRUG MONITORING
Provisionally accepted
Javier López Hernández1
Ana Belén Guisado Gil1,2,3,4
Marta Mejías Trueba2,3,4,5*
Laura Herrera Hidalgo1,2,3,4Francisco Javier Reina Martínez6María Victoria Gil Navarro1,3,4- 1Department of Pharmacy, Virgen del Rocío University Hospital, Seville, Spain
- 2Department of Infectious Diseases, Microbiology and Parasitology, Virgen del Rocío University Hospital, Seville, Spain
- 3Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
- 4Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain, Seville, Spain
- 5Virgen del Rocío University Hospital, Seville, Spain
- 6Intensive Care Medicine Department, Virgen del Rocío University Hospital, Seville, Spain
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Voriconazole is a triazole antifungal used for invasive fungal infections, particularly invasive aspergillosis. Its metabolism is primarily mediated by CYP2C19, with CYP3A4 and CYP2C9 also involved. Nirmatrelvir/ritonavir, an oral antiviral for COVID-19, inhibits CYP isoforms potentially altering the metabolism of co-administered drugs. We report a case of an immunosuppressed patient with SARS-CoV-2 pneumonia and invasive aspergillosis treated with voriconazole and nirmatrelvir/ritonavir. Unexpectedly, voriconazole plasma concentrations increased significantly (7.78 mg/L) instead of the anticipated decrease, leading to temporary discontinuation. Therapeutic drug monitoring (TDM) guided dose adjustments until optimal levels (2 mg/L) were achieved. After 13 days, the patient recovered from COVID-19, with clinical improvement of aspergillosis. This case highlights the importance of pharmacokinetic monitoring and drug-drug interaction assessment in critically ill patients.
Keywords: MeSH): Voriconazole, Aspergillosis, COVID-19, drug-drug interactions, Therapeutic drug monitoring
Received: 22 Apr 2025; Accepted: 02 Jun 2025.
Copyright: © 2025 López Hernández, Guisado Gil, Mejías Trueba, Herrera Hidalgo, Reina Martínez and Gil Navarro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Marta Mejías Trueba, Virgen del Rocío University Hospital, Seville, Spain
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