Coadministration has not been studied Neratinib is metabolised mainly by CYP3A4 and to a lesser extent by flavin-containing monooxygenase (FMO). Concentrations are expected to increase significantly due to strong inhibition of CYP3A4 by nirmatrelvir/ritonavir. Ketoconazole (a strong CYP3A4 inhibitor) increased neratinib AUC by 4.8-fold. Coadministration is contraindicated in the product labels for nirmatrelvir/ritonavir due to serious and/or life-threatening potential reactions including hepatotoxicity. The decision to pause neratinib should be made in conjunction with the patient’s oncologist. If it is decided to pause neratinib, start nirmatrelvir/ritonavir treatment 24 hours after the last neratinib dose due to the long elimination half-life of neratinib. Restart neratinib 3 days after completing nirmatrelvir/ritonavir treatment given that CYP3A4 inhibition by ritonavir takes several days to resolve.