Pharmacokinetic Interactions Between Elbasvir/Grazoprevir and Immunosuppressant Drugs in Healthy Volunteers

Elbasvir (EBR)/grazoprevir (GZR) may be coadministered with immunosuppressant drugs in posttransplant people who are infected with hepatitis C virus. The aim of the present study was to assess the safety and pharmacokinetic interactions between EBR and GZR and single doses of cyclosporine, tacrolimus, mycophenolate mofetil (MMF), and prednisone. This was a 4-part, open-label study in 58 healthy volunteers. Participants received single doses of cyclosporine 400mg, tacrolimus 2mg, MMF 1 g, or prednisone 40mg alone or in the presence of once-daily EBR 50mg/GZR 200mg. Multiple oral doses of EBR + GZR had no significant effect on cyclosporine. However, in the presence of cyclosporine, the 24-hour area under the concentration-time curve of GZR was increased by approximately 15-fold (geometric mean ratio [90%CI] 15.21 [12.83; 18.04]); the concentration of EBR was increased approximately 2-fold in the presence of cyclosporine. Coadministration of EBR/GZR and tacrolimus did not affect the pharmacokinetics of EBR or GZR, but resulted in an increase in tacrolimus AUC (geometric mean ratio [90%CI] 1.43 [1.24; 1.64]). There were no clinically relevant interactions between EBR/GZR and either MMF or prednisone. Data from the present study indicate that EBR/GZR may be coadministered in people receiving tacrolimus, MMF, and prednisolone. EBR/GZR is contraindicated in people receiving cyclosporine because the significantly higher concentrations of GZR may increase the risk of transaminase elevations.