Coadministration has not been studied. Fostamatinib is metabolised in the gut by alkaline phosphatase to the major active metabolite, R406, which is then metabolised by CYP3A4 and UGT1A9. Coadministration of ketoconazole, a strong CYP3A4 inhibitor (200 mg twice daily for 3.5 days) with fostamatinib (80 mg single dose; 0.53 times the 150 mg dose) increased R406 AUC and Cmax by 102% and 37%. Increased R406 exposure may increase the risk of adverse reactions (i.e., diarrhoea, hypertension, hepatotoxicity and neutropenia). Consider a two-fold reduction in fostamatinib dose frequency (i.e., from 150 mg twice daily to 150 mg once daily or 100 mg twice daily to 100 mg once daily) when coadministered with nirmatrelvir/ritonavir. Resume fostamatinib dose that was used prior to nirmatrelvir/ritonavir 3 days after completing nirmatrelvir/ritonavir treatment given that CYP3A4 inhibition by ritonavir takes several days to resolve. If significant toxicity occurs, consider interruption of fostamatinib with reintroduction 3 days after completing nirmatrelvir/ritonavir treatment.