midostaurin + itraconazole

This is a **combination of midostaurin and itraconazole**, two small-molecule pharmaceuticals occasionally coadministered in clinical practice, especially in patients with acute myeloid leukemia (AML) and systemic mastocytosis to treat cancer and prevent fungal infections, respectively. - **Midostaurin** is a multi-kinase inhibitor targeting FLT3 and other tyrosine kinases, indicated for FLT3-mutated AML and advanced systemic mastocytosis. It works by inhibiting kinase-mediated signaling, which is crucial for cancer cell proliferation and survival. - **Itraconazole** is a triazole antifungal agent that inhibits fungal cytochrome P450-dependent enzyme 14α-demethylase, blocking ergosterol synthesis and thus the integrity of the fungal cell membrane. Importantly, itraconazole is a strong inhibitor of CYP3A4, the main enzyme that metabolizes midostaurin. Coadministration significantly increases midostaurin exposure, which raises the potential for increased toxicity; thus, this combination is clinically significant due to pharmacokinetic drug-drug interaction concerns. Product labeling generally recommends avoiding this combination or close monitoring for toxicity if used. There is no approved fixed-dose combination product; this refers to coadministration of the separately marketed drugs[1][3][4].