Effects of the Japanese Kampo Medicines Rikkunshito, Shakuyakukanzoto and Goreisan on Lenvatinib Plasma Concentrations in Japanese Patients with Thyroid Cancer

BackgroundKampo medicines are often used in Japan as therapy for the side effects induced by oral kinase inhibitors. However, the pharmacokinetic interactions between Kampo medicines and oral kinase inhibitors such as lenvatinib have not been studied.ObjectiveWe investigated the effects of Kampo medicines (rikkunshito, shakuyakukanzoto and goreisan) on the steady-state plasma trough concentration (C0) of lenvatinib in patients with thyroid cancer.MethodsThirty-nine patients receiving lenvatinib therapy at Ito Hospital between May 2015 and December 2019 were enrolled. The mean C0 of lenvatinib with Kampo medicine, at the same dose as before initiating Kampo medicines, was used.ResultsAfter the repeated administration of rikkunshito (n = 21), shakuyakukanzoto (n = 10) or goreisan (n = 8), the mean C0 of lenvatinib and the laboratory test values of patients did not change significantly. In contrast to rikkunshito, which alleviates emesis by enhancing gastric emptying, the C0 values of lenvatinib with a proton pump inhibitor (PPI) (n = 16) or histamine H2 receptor antagonist (H2RA) (n = 4) were significantly lower than the C0 values without a PPI or H2RA (P = 0.007). The mean (range) change rate of the C0 of lenvatinib with a PPI or H2RA versus without a PPI or H2RA was 88.6% (69.9-115%), and was significantly greater than the change rate for rikkunshito (P = 0.029). There was no significant difference between the C0 of lenvatinib with a prokinetic agent (n = 7) versus without a prokinetic agent (P = 0.365).ConclusionsAlthough these Kampo medicines are reported to inhibit drug-metabolizing enzymes and drug transporters, the risk of drug interactions for patients receiving lenvatinib therapy is low. Patients should feel confident that they can receive Kampo medicines as supportive care for lenvatinib therapy without a risk of drug interactions that could affect treatment efficacy.