Coadministration with nirmatrelvir/ritonavir has not been studied. Ribociclib is metabolised by CYP3A4. Coadministration of ritonavir (100 mg twice daily for 14 days) and ribociclib (400 mg single dose) increased ribociclib AUC and Cmax by 221% and 67% in healthy subjects. Coadministration with strong CYP3A4 inhibitors (such as nirmatrelvir/ritonavir) is not recommended. The decision to pause or dose-adjust ribociclib should be made in conjunction with the patient’s oncologist. If it is decided to pause ribociclib, start nirmatrelvir/ritonavir 24 hours after the last dose of ribociclib due to the long elimination half-life of ribociclib. Restart ribociclib 3 days after completing nirmatrelvir/ritonavir treatment given that CYP3A4 inhibition by ritonavir takes several days to resolve. Alternatively, if coadministration is necessary, consider reducing ribociclib dose to 400 mg once daily (in patients on 600 mg ribociclib) or to 200 mg (in patients who had their dose reduced to 400 mg) or interrupt ribociclib (in patients who have had their dose reduced to 200 mg) with close monitoring for toxicity.