dasatinib + ketoconazole

Dasatinib is an orally available small molecule tyrosine kinase inhibitor primarily used for the treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). It inhibits multiple kinases, including BCR-ABL, SRC family kinases, c-KIT, EPHA2, and PDGFRβ. Ketoconazole is a broad-spectrum antifungal agent that acts by inhibiting fungal ergosterol synthesis via inhibition of cytochrome P450 14α-demethylase. When coadministered, ketoconazole—a potent CYP3A4 inhibitor—markedly increases dasatinib plasma concentrations by inhibiting its metabolism. This combination can increase the risk of adverse effects such as QT prolongation and pleural effusion; therefore, concurrent use should be avoided or closely monitored with dose adjustments if necessary[3][4][5].