Coadministration with has not been studied. Trazodone is primarily metabolized by CYP3A4. Nirmatrelvir/ritonavir could potentially increase trazodone concentrations. The combination should be used with caution and a lower dose of trazodone should be considered. In healthy volunteers, ritonavir (200 mg twice daily) increased trazodone concentrations by more than two-fold leading to nausea, syncope and hypotension. Caution is also needed as trazodone has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. After stopping nirmatrelvir/ritonavir, the CYP3A4 inhibitory effect of nirmatrelvir/ritonavir is predicted to mostly disappear after 3 days.