Interactions of capmatinib with other drugs

Capmatinib as a targetedMET inhibitor, when used to treat patients with non-small cell lung cancer with MET exon 14 skipping mutations, the possible interactions between it and other drugs are an important clinical issue that cannot be ignored. Drug interactions may not only change the efficacy of capmatinib, but may also aggravate toxic reactions, so a comprehensive drug history evaluation is required before use.

Capmatinib is mainly metabolized by CYP3A4 enzyme and is also a substrate of P-glycoprotein, so there is a significant interaction with inhibitors or inducers of CYP3A4. For example, when combined with strong CYP3A4 inhibitors such as ketoconazole and clarithromycin, the plasma concentration of capmatinib may increase, increasing the risk of adverse reactions, such as abnormal liver function, fatigue, vomiting, etc. On the contrary, if it is used together with enzyme inducers such as rifampicin and phenytoin, the concentration of capmatinib may decrease and the efficacy will be reduced. Therefore, coadministration of such drugs should be avoided or dosage monitoring required.

In addition, capmatinib may affect the metabolism of other drugs itself, especially by inhibitingOCT2 and MATE1 transporters, which may enhance the accumulation of drugs such as methotrexate, gefitinib, ranitidine and other drugs in the body, so be wary of increased drug toxicity.

In the context of anti-cancer combination therapy, if immune checkpoint inhibitors, platinum-based chemotherapy drugs or other targeted drugs need to be used simultaneously, drug interaction effects and the risk of toxicity must be assessed. Although there are no large head-to-head studies, conservative adjustment of capmatinib dose in combination regimens and close monitoring of liver and kidney function, electrolytes, and blood cell counts are recommended.

In terms of diet, although capmatinib can be taken with meals, you should avoid ingesting grapefruit and its products at the same time, because the ingredients in such foods can inhibitCYP3A4 activity and further interfere with the metabolism of capmatinib.

Reference materials:https://www.drugs.com/mtm/capmatinib.html