Coadministration has not been studied and is not recommended. Rivaroxaban is partly metabolized in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine (by P-gp and BCRP). Nirmatrelvir/ritonavir is a strong inhibitor of both CYP3A4 and P-gp and is expected to increase rivaroxaban plasma concentrations which may increase the risk of bleeding. The product labels for rivaroxaban do not recommend the concomitant use with strong CYP3A4 and P-gp inhibitors. Use an alternative COVID-19 therapy. If nirmatrelvir/ritonavir treatment is needed, pause rivaroxaban and use alternative options for anticoagulation based on the indication. For the treatment of atrial fibrillation, consider switching to edoxaban at 30 mg once daily. For patients at high risk of venous/arterial thromboembolism (VTE/ATE), consider switching to low molecular weight heparin (LMWH). For patient with a lower risk of VTE/ATE, consider switching to aspirin. The usual rivaroxaban treatment should be resumed 3 days after the last dose of nirmatrelvir/ritonavir. The decision to pause rivaroxaban and give edoxaban, LMWH or aspirin should be made on a case-by-case basis. Note: a PBPK modelling study showed that a decrease in rivaroxaban dose to 10 mg daily during nirmatrelvir/ritonavir treatment (and up to 3 days post completion of nirmatrelvir/ritonavir treatment) could maintain an acceptable systemic exposure of rivaroxaban. Importantly, the estimated risk of major bleeding for rivaroxaban 10 mg plus nirmatrelvir/ritonavir vs rivaroxaban 15-20 mg alone was similar for the general population with normal renal function (3.4% vs 3.3%) and slightly increased in the general population with moderate renal impairment (5.5% vs 4.5%) suggesting that a dosage adjustment of rivaroxaban could be acceptable in the general population. However, the estimated risk of major bleeding was further increased in the geriatric population with normal renal function (6.4% vs 4.9%) and the geriatric population with moderate renal impairment (10.5% vs 6.1%) suggesting that rivaroxaban in presence of nirmatrelvir/ritonavir should preferably be avoided in the geriatric population.