When 240 mg of neratinib was given

When 240 mg of neratinib was given with the CYP3A4 inducer rifampin, neratinib Cmax and AUC were significantly decreased to 24% and 13% respectively of those values when neratinib administrated alone. The ratios of active metabolites M6 and M7 were also reduced to 50-63% based on the AUC values. By converting to molar concentration based AUCs and combining relative activities of HER2 inhibition for neratinib and each active metabolites, there is ~74% reduction of the combined activity exposures when given with the CYP3A4 inducer rifampin (Table 8 below). Thus, the concomitant use of neratinib with strong or moderate CYP3A inducers should be avoided.