Coadministration has not been studied. Apixaban is a substrate of P-gp and is metabolized by CYP3A4. Concentrations of apixaban are expected to increase due to CYP3A4 and P-gp inhibition by ritonavir. The product labels for apixaban do not recommend the concomitant use with strong dual CYP3A4 and P-gp inhibitors, although the US label for apixaban gives the option to use apixaban at a reduced dose (i.e., 2.5 mg) if needed. Of interest, no adverse outcomes were reported in six HIV infected patients treated with a reduced dose of apixaban (2.5 mg twice daily) while on ritonavir boosted regimens suggesting that a reduced dose of apixaban could be used with nirmatrelvir/ritonavir. If nirmatrelvir/ritonavir treatment is needed, consider adjusting apixaban dosage according to risk, indication and current dose. For treatment of atrial fibrillation with standard apixaban dose (i.e., 5 mg twice daily), reduce apixaban to 2.5 mg twice daily. For treatment of atrial fibrillation with low dose apixaban (i.e., 2.5 mg twice daily), continue low dose on a case-by-case basis. For patients at high risk of venous/arterial thromboembolism (VTE/ATE), consider switching from apixaban to low molecular weight heparin (LMWH); patients with a lower risk of VTE/ATE could be switched to aspirin on a case-by-case basis. The usual apixaban treatment should be resumed 3 days after the last dose of nirmatrelvir/ritonavir.