Clinically relevant bidirectional drug-drug interaction between midostaurin and voriconazole.
Details
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_9BC838D4B328
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Clinically relevant bidirectional drug-drug interaction between midostaurin and voriconazole.
Journal
British journal of clinical pharmacology
ISSN
1365-2125 (Electronic)
ISSN-L
0306-5251
Publication state
Published
Issued date
07/2023
Peer-reviewed
Oui
Volume
89
Number
7
Pages
2304-2308
Language
english
Notes
Publication types: Case Reports
Publication Status: ppublish
Publication Status: ppublish
Abstract
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-drug 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-year-old 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 (C <sub>trough</sub> 10.3 mg L <sup>-1</sup> , target C <sub>trough</sub> 1-5 mg L <sup>-1</sup> ). Neurotoxicity was considered to be related to voriconazole overexposure. The concentration of midostaurin was concomitantly six-fold 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-drug interactions between midostaurin and azole antifungals. Close clinical and therapeutic drug monitoring is advised in such cases.
Keywords
Female, Humans, Middle Aged, Voriconazole/adverse effects, Voriconazole/pharmacokinetics, Antifungal Agents/adverse effects, Drug Interactions, Leukemia, Myeloid, Acute/drug therapy, Hallucinations, acute myeloid leukaemia, cytochrome, drug-drug interaction, midostaurin, voriconazole
Pubmed
Web of science
Open Access
Yes
Create date
17/04/2023 13:11
Last modification date
06/08/2024 7:02