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Drug Interaction Voriconazole-Ibrutinib — SCE Infectious Diseases MCQ

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HardFungal InfectionsDrug Interaction Voriconazole-IbrutinibSCE Infectious Diseases

A 60-year-old man with a recent diagnosis of CLL on Ibrutinib develops invasive pulmonary aspergillosis. His haematologist asks about the drug interaction between Voriconazole and Ibrutinib. What is the clinical significance?

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Correct answer: E — Voriconazole inhibits CYP3A4, dramatically increasing Ibrutinib levels and toxicity risk (bleeding, arrhythmia); dose reduction or alternative antifungal required

Voriconazole is a potent CYP3A4 inhibitor. Ibrutinib is primarily metabolised by CYP3A4. Co-administration increases Ibrutinib AUC by up to 24-fold, dramatically increasing the risk of toxicity: bleeding (Ibrutinib inhibits platelet function), atrial fibrillation, and other adverse effects. Options include: using an alternative antifungal with less CYP3A4 inhibition (Isavuconazole is preferred — less CYP3A4 inhibition), or significantly reducing the Ibrutinib dose with close monitoring. Posaconazole has a similar interaction profile.

Reference: BNF 2024 – Ibrutinib interactions; BSAC 2024 – Antifungal guidelines