{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T18:08:57Z","timestamp":1767982137638,"version":"3.49.0"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:p>Midostaurin is often prescribed with azole antifungals in patients with leukaemia, either for aspergillosis prophylaxis or treatment. Midostaurin is extensively metabolized by cytochrome (CYP) 3A4. In addition, it inhibits and induces various CYPs at therapeutic concentrations. Thus, midostaurin is associated with a high potential for drug\u2010drug interactions (DDIs), both as a substrate (victim) and as a perpetrator. However, data on midostaurin as a perpetrator of DDIs are scarce, as most pharmacokinetic studies have focused on midostaurin as a victim drug. We report a clinically relevant bidirectional DDI between midostaurin and voriconazole during induction treatment. A 49\u2010year\u2010old woman with acute myeloid leukaemia developed invasive pulmonary aspergillosis after induction chemotherapy. She was treated with voriconazole at standard dosage. Six days after starting midostaurin, she developed visual hallucinations with a concurrent sharp increase in voriconazole blood concentration (<jats:italic>C<\/jats:italic><jats:sub>trough<\/jats:sub> 10.3\u2009mg\u2009L<jats:sup>\u22121<\/jats:sup>, target <jats:italic>C<\/jats:italic><jats:sub>trough<\/jats:sub> 1\u20105\u2009mg\u2009L<jats:sup>\u22121<\/jats:sup>). Neurotoxicity was considered to be related to voriconazole overexposure. The concentration of midostaurin was concomitantly six\u2010fold above the average expected level, but without safety issues. Midostaurin was stopped and the dosage of voriconazole was adjusted with therapeutic drug monitoring. The evolution was favourable, with quick resolution and no recurrence of visual hallucinations. To our knowledge, this is the first case suggesting that midostaurin and voriconazole reciprocally inhibit each other's metabolism, leading to increased exposure of both. This case highlights the knowledge gap regarding drug\u2010drug interactions between midostaurin and azole antifungals. Close clinical and therapeutic drug monitoring is advised in such cases.<\/jats:p>","DOI":"10.1111\/bcp.15743","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T05:32:35Z","timestamp":1681363955000},"page":"2304-2308","source":"Crossref","is-referenced-by-count":5,"title":["Clinically relevant bidirectional drug\u2010drug interaction between midostaurin and voriconazole"],"prefix":"10.1111","volume":"89","author":[{"given":"David","family":"Haefliger","sequence":"first","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2312-7050","authenticated-orcid":false,"given":"Catia","family":"Marzolini","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research University Hospital Basel  Basel Switzerland"},{"name":"Faculty of Medicine University of Basel  Basel Switzerland"},{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederic","family":"Lamoth","sequence":"additional","affiliation":[{"name":"Service of Infectious Diseases Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"},{"name":"Institute of Microbiology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Pabst","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital University Hospital  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Buclin","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7427-5953","authenticated-orcid":false,"given":"Francoise","family":"Livio","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Accessed March 9 2023.https:\/\/www.medicines.org.uk\/emc\/product\/9134\/smpc\/print#INDICATIONS"},{"key":"e_1_2_9_3_1","unstructured":"Food and Drug Administration. 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