{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:31:34Z","timestamp":1785148294216,"version":"3.55.0"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>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\u00a0mg\/L) instead of the anticipated decrease, leading to temporary discontinuation. Therapeutic drug monitoring (TDM) guided dose adjustments until optimal levels (2\u00a0mg\/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.<\/jats:p>","DOI":"10.3389\/fphar.2025.1616061","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T07:41:26Z","timestamp":1749714086000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Unexpected voriconazole toxicity due to nirmatrelvir\/ritonavir: a case report on drug-drug interaction and the role of therapeutic drug monitoring"],"prefix":"10.3389","volume":"16","author":[{"given":"J.","family":"L\u00f3pez-Hern\u00e1ndez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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V.","family":"Gil-Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"B1","unstructured":"Paxlovid\n          \n          \n          2022"},{"key":"B2","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1097\/FPC.0000000000000276","article-title":"PharmGKB summary: voriconazole pathway, pharmacokinetics","volume":"27","author":"Barbarino","year":"2017","journal-title":"Pharmacogenet Genomics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"S1130","DOI":"10.1016\/j.farma.2023.02.003","article-title":"Paradoxical interaction between nirmatrelvir\/ritonavir and voriconazole in a patient with COVID-19","volume":"21","author":"Bayo","year":"2023","journal-title":"Farm Hosp."},{"key":"B4","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1093\/infdis\/jiad393","article-title":"Nirmatrelvir\/ritonavir use and hospitalizations or death in a previously uninfected nonhospitalized high-risk population with COVID-19: a matched cohort study","volume":"229","author":"Butt","year":"2024","journal-title":"J. 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