sulting in adverse events. Both velpatasvir and ranolazine are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). Ranolazine is also a weak in vitro inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Regorafenib: Use caution if coadministration of regorafenib with sofosbuvir is necessary, and monitor for an increase in sofosbuvir-related adverse reactions. Sofosbuvir is a BCRP substrate, and regorafenib is a BCRP inhibitor. Administration of regorafenib for 14 days prior to a single dose of rosuvastatin, another BCRP substrate, increased the mean AUC and Cmax of rosuvastatin by 3.8-fold and a 4.6-fold, respectively. Concomitant use may increase exposure to sofosbuvir. Use caution when administering velpatasvir with regorafenib. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of BCRP; regorafenib is a BCRP inhibitor. Administration of regorafenib for 14 days prior to a single dose of rosuvastatin, another BCRP substrate, increased the mean AUC and Cmax of rosuvastatin by 3.8-fold and a 4.6-fold, respectively; regorafenib-mediated BCRP inhibition may also increase exposure to velpatasvir. Velpatasvir is also a CYP2B6 substrate and regorafenib inhibits CYP2D6 in vitro, which may further increase exposure to velpatasvir.
Rifabutin: Avoid coadministration of sofosbuvir with rifabutin. Taking these drugs together may decrease sofosbuvir plasma concentration, potentially resulting in loss of antiviral efficacy. Avoid coadministration of velpatasvir with inducers of CYP3A4, such as rifabutin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate.
Rifampin: Avoid coadministration of sofosbuvir, a P-glycoprotein (P-gp) substrate, with inducers of P-gp, such as rifampin. Taking these drugs together may significantly decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the sofosbuvir Cmax and AUC to 23% and 28% of normal concentrations, respectively. Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp), CYP3A4, CYP2B6, and CYP2C8, such as rifampin. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In a single-dose study, coadministration reduced the velpatasvir Cmax and AUC to 29% and 18% or normal concentrations, respectively. Velpatasvir is a substrate of P-gp, CYP3A4, CYP2B6, and CYP2C8.
Rifapentine: Avoid coadministration of sofosbuvir with rifapentine. Taking these drugs together may decrease sofosbuvir plasma concentration, potentially resulting in loss of antiviral efficacy. Avoid coadministration of velpatasvir with inducers of CYP3A4 and CYP2C8, such as rifapentine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 and CYP2C8 substrate.
Rifaximin: Although the clinical significance of this interaction is unknown, concurrent use of rifaximin with velpatasvir may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. Rifaximin is a substrate |
