lorlatinib + itraconazole

Lorlatinib + itraconazole refers to the co-administration of lorlatinib, a third-generation oral small molecule inhibitor of anaplastic lymphoma kinase (ALK) and ROS1 used in ALK-positive metastatic non-small cell lung cancer (NSCLC), and itraconazole, an oral triazole antifungal agent used for various systemic and superficial fungal infections. Lorlatinib acts as a highly selective inhibitor targeting ALK and ROS1 tyrosine kinases, leading to inhibition of tumor cell proliferation in ALK-rearranged and ROS1-rearranged NSCLC. Itraconazole inhibits fungal ergosterol synthesis via potent inhibition of lanosterol 14α-demethylase (CYP51). The combination is not an approved therapy but is relevant for drug-drug interaction considerations: itraconazole, a strong CYP3A inhibitor, significantly increases lorlatinib exposure, which necessitates dose adjustments if combined.