Orelabrutinib + Itraconazole

Orelabrutinib is a small molecule Bruton’s tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. It works by selectively and irreversibly inhibiting BTK, a key enzyme in the B-cell receptor signaling pathway that is critical for the survival and proliferation of malignant B cells. Itraconazole is a triazole antifungal agent used to treat various serious fungal infections such as aspergillosis, blastomycosis, histoplasmosis, and onychomycosis. It acts by inhibiting fungal cytochrome P450-dependent enzyme lanosterol 14α-demethylase (CYP51A1), thereby disrupting ergosterol synthesis and compromising fungal cell membrane integrity[3][5][7]. Itraconazole also inhibits drug transporters such as P-glycoprotein and breast cancer resistance protein (BCRP)[8]. The combination of orelabrutinib with itraconazole may be considered in clinical settings where both antifungal prophylaxis/treatment and BTK inhibition are required.