Dose adjustments are not necessary for patients with gastrointestinal stromal tumors (GISTs) when they are given ripretinib with gastric acid reducers and strong CYP3A inhibitors, according to a study published in Clinical Pharmacology in Drug Development.

The researchers assessed the drug-drug interaction potentials of ripretinib with 3 other drugs: itraconazole, rifampin, and pantoprazole. They said that patients who are treated with strong CYP3A inhibitors like itraconazole should be monitored more frequently for adverse reactions.

“Concomitant ripretinib use with strong CYP3A inducers should be avoided,” they wrote. For specific dose recommendations with concomitant use with this type of drug, clinicians should use the approved labeling, they said.

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The open-label, fixed-sequence study included a total of 69 patients. Of these, 20 were given 50 mg of ripretinib alone or in combination with 200 mg of itraconazole once a day, 24 patients were given 100 mg of ripretinib alone or in combination with 600 mg of rifampin once a day, and 25 patients were given 50 mg of ripretinib alone or in combination with 40 mg of pantoprazole once a day.

The results of the study showed that ripretinib exposure increased when it was used together with itraconazole. Inversely, it decreased when it was used together with rifampin. Using ripretinib together with pantoprazole had no effect on its pharmacokinetics, and there were no unexpected safety signals during the study.

Ripretinib is a switch control KIT kinase inhibitor. It is approved by the US Food and Drug Administration for the treatment of adult patients with advanced GISTs who were previously treated with 3 or more kinase inhibitors.

Itraconazole is a strong CYP3A inhibitor, rifampin is a strong CYP3A inducer, and pantoprazole is a proton pump inhibitor.


Li X, Shelton MJ, Wang J, Meade J, Ruiz-Soto R. Effects of CYP3A inhibition, CYP3A induction, and gastric acid reduction on the pharmacokinetics of ripretinib, a switch control KIT tyrosine kinase inhibitor. Clin Pharmacol Drug Dev. Published online May 13, 2022. doi:10.1002/cpdd.1110