of the drug transporters P-glycoprotein (P-gp) and organic anion transporting polypeptides OATP1B1 and OATP1B3; velpatasvir is a P-gp, OATP1B1, and OATP1B3 inhibitor. During one in vitro study, coadministration with a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
Ritonavir: Avoid coadministration of velpatasvir with ritonavir. Taking these drugs together may significantly alter the plasma concentrations of velpatasvir, and increase the concentrations of ritonavir. Velpatasvir is a CYP3A4 substrate. Ritonavir is a mixed inducer/inhibitor of CYP3A4. In addition, both ritonavir and velpatasvir are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). If these drugs are administered together, monitor for loss of antiviral efficacy and adverse effects. Caution is warranted when ritonavir is administered with sofosbuvir as there is a potential for elevated concentrations of sofosbuvir. Ritonvir is an inhibitor of the transporter P-glycoprotein (P-gp). Sofosbuvir is a substrate of P-gp. According to the manufacturer, no dosage adjustments are required when sofosbuvir is administered concurrently with P-gp inhibitors; however, if these drugs are given together, consider increased monitoring for potential adverse effects.
Rolapitant: Use caution if sofosbuvir and rolapitant are used concurrently, and monitor for sofosbuvir-related adverse effects. Sofosbuvir is a substrate of the Breast Cancer Resistance Protein (BCRP) and P-glycoprotein (P-gp), where an increase in exposure may significantly increase adverse effects; rolapitant is a BCRP and P-gp inhibitor. The Cmax and AUC of another BCRP substrate, sulfasalazine, were increased by 140% and 130%, respectively, on day 1 with rolapitant, and by 17% and 32%, respectively, on day 8 after rolapitant administration. When rolapitant was administered with digoxin, a P-gp substrate, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied. Use caution when administering velpatasvir with rolapitant. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); rolapitant is an inhibitor of both P-gp and BCRP.
Rosuvastatin: Do not exceed a rosuvastatin dose of 10 mg daily with coadministration of velpatasvir as this may significantly increase the serum concentrations of rosuvastatin, which may increase the risk of myopathy and rhabdomyolysis. Rosuvastatin is a substrate of the breast cancer resistance protein (BCRP) and OATP1B1 transporters, while velpatasvir inhibits both BCRP and OATP1B1.
Sapropterin: Caution is advised with the concomitant use of sapropterin and sofosbuvir as coadministration may result in increased systemic exposure of sofosbuvir. Sofosbuvir is a substrate for the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); in vitro data show that sapropterin may inhibit these transporters. If these drugs are used together, closely monitor for increased side effects of sofosbuvir. Caution is advised with the concomitant use of sapropterin and velpatasvir as coadministration may result in inc |
