Fostamatinib is a prodrug rapidly cleaved by alkaline phosphatase in the intestine to its active moiety R406. R406 has a high protein binding ratio and is mainly metabolized by cytochrome P450 3A4 and UGT1A9 in the liver and excreted into feces.

R406 is a substrate of P-glycoprotein, whereas fostamatinib and R406 inhibit breast cancer resistance protein with high intestinal concentration/IC50 values. Great attention should be paid to the drug–drug interactions with the substrates of these transporters, especially statins.

Fostamatinib dosage can be increased during treatment. Whereas a R406 exposure-dependent increase in efficacy was not clear; a significant correlation between systemic exposure and adverse events such as hypertension has been reported. During the dose escalation, careful management is required to avoid toxicity-related treatment discontinuation.