imatinib + methotrexate

Combination of **imatinib**, a small molecule tyrosine kinase inhibitor that targets BCR-ABL and other kinases, and **methotrexate**, a folate antimetabolite and antineoplastic agent that inhibits dihydrofolate reductase. This combination is primarily used in the treatment of **Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)** as part of multi-agent chemotherapy regimens. Imatinib inhibits BCR-ABL tyrosine kinase, thereby blocking proliferation of leukemic cells, while methotrexate impairs DNA synthesis and cell replication. Combination therapy carries an increased risk of delayed methotrexate clearance and acute kidney injury, possibly due to pharmacokinetic interactions involving transporter proteins such as OATP1A2 and OATP1B3, and possibly ABC transporters. This combination necessitates careful monitoring and may require adjusted supportive therapy (e.g., enhanced hydration, leucovorin rescue)[1][6][7].