milademetan + posaconazole

Milademetan + posaconazole is a co-administration of the investigational MDM2 inhibitor milademetan and the antifungal agent posaconazole. Milademetan is an oral small molecule that inhibits murine double minute 2 (MDM2), thereby reactivating p53 tumor suppressor pathways, and is being developed primarily for advanced solid tumors and hematological malignancies, including liposarcoma and acute myeloid leukemia. Posaconazole is an oral triazole antifungal agent that inhibits fungal lanosterol 14α-demethylase, thus impairing ergosterol synthesis and disrupting fungal cell membrane formation. This combination is not a branded combination product but reflects clinical scenarios where milademetan is co-administered with posaconazole, particularly relevant due to strong CYP3A4 inhibition by posaconazole, which dramatically increases milademetan exposure (AUC increased by ~2.5-fold). Close monitoring, dose modifications, and safety precautions are necessary in this combination due to the significant pharmacokinetic interaction[1].