lorlatinib + modafinil

This is a **combination of lorlatinib**, a third-generation anaplastic lymphoma kinase (ALK) and ROS1 tyrosine kinase inhibitor, and **modafinil**, a moderate cytochrome P450 (CYP) 3A inducer primarily used for sleep-wake disorders. Lorlatinib is metabolized by CYP3A and is indicated for advanced ALK-positive non-small cell lung cancer. Co-administration with modafinil, a moderate CYP3A inducer, reduces lorlatinib exposure (AUC and Cmax decreased by approximately 23% and 22%, respectively) but does not result in clinically meaningful hepatotoxicity or safety concerns based on phase I studies in healthy participants. The combined use is generally well tolerated in healthy adults, with adverse effects related mainly to modafinil, and no significant changes in liver function tests during combination administration. This combination is not an approved therapy for any indication but has been evaluated to assess pharmacokinetics and safety interactions between the two drugs[1][2][3][4].