Variability in belumosudil exposure due to coadministration of voriconazole and isavuconazole in a patient with chronic graft-versus-host disease: Case report.
Mari Shimoda, Yoshito Gando, Saori Aizawa et al.
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Case in brief
A man in his 50s with steroid-refractory pulmonary chronic graft-versus-host disease after cord blood transplantation received belumosudil, increased from 200 mg once daily to 200 mg twice daily. Voriconazole was changed to isavuconazole because of elevated galactomannan levels and grade 2 hepatotoxicity. Across 28 plasma samples collected 2 hours after belumosudil dosing, median concentrations were higher during voriconazole coadministration than during isavuconazole coadministration (889.88 vs. 395.96 ng/mL; p < 0.001).
What made this case unusual
Serial within-patient measurements showed substantially different belumosudil concentrations with two azoles of differing CYP3A4 inhibition strength, providing a clinical comparison during treatment.
Diagnostic / clinical pearl
When interpreting belumosudil exposure in a patient receiving an azole, account for the antifungal’s CYP3A4 inhibition strength; this case found higher concentrations with voriconazole than with isavuconazole.
Why it matters
The report supports considering therapeutic drug monitoring and careful antifungal selection when combining belumosudil with azoles, while also accounting for absorption and hepatic function.