Summary of important mechanism-based DDI predictions and clinical observations of the 3D regimen

DDI PredictionsClinical ObservationsDDI PredictionsClinical Observations
CYP3ARitonavirRitonavir↓ 3D regimen with strong inducers↓ 3D regimen with carbamazepine
↑ Sensitive substrates↑ Paritaprevir and tacrolimus3D regimen with strong inhibitors3D regimen with ketoconazole
CYP2C8None↑ Dasabuvir with strong inhibitors↑ Dasabuvir with gemfibrozil
CYP2C19Ritonavir and dasabuvirRitonavirNone
Sensitive substratesa↓ Omeprazoleb
OATP1B1 and OATP1B3ParitaprevirParitaprevir↑ Paritaprevir with strong inhibitors↑ Paritaprevirb with atazanavir
↑ Sensitive substrates↑ Pravastatin
BCRPParitaprevirParitaprevir↑ 3D regimen with strong inhibitors↑ 3D regimenb with cyclosporine
↑ Sensitive substrates↑ Rosuvastatin
UGT1A13D regimen3D regimenNone
↑ Sensitive substrates↑ Raltegravirb
  • Upward arrows, downward arrows, and horizontal arrows indicate an increase, decrease, or no change in systemic exposure, respectively. Dashes indicate that the mechanism was not tested in dedicated clinical trials. Additional information on coadministered drugs with the 3D regimen: carbamazepine (strong CYP3A inducer), ketoconazole (strong CYP3A inhibitor), gemfibrozil (strong CYP2C8 inhibitor), atazanavir (OATP and CYP3A inhibitor), cyclosporine (OATP, P-gp, and BCRP inhibitor), pravastatin (OATP1B1 and OATP1B3 substrate), rosuvastatin (OATP and BCRP substrate), and raltegravir (UGT1A1 substrate).

  • a CYP2C19 induction was not considered in DDI predictions, due to unavailability of model parameters EC50 and Emax for ritonavir.

  • b The change in exposure is not clinically relevant (Badri et al., 2015; Khatri et al., 2016).