and BCRP. Olaparib is an in vitro P-gp and BCRP inhibitor, although the clinical relevance is unknown. The FDA-labeling of sofosbuvir suggests that inhibitors of P-gp and BCRP may be coadministered with sofosbuvir. In clinical trials, no clinically significant interaction was noted when sofosbuvir was administered with darunavir/ritonavir (P-gp inhibitors) or cyclosporine (a P-gp and BCRP inhibitor). Use caution if coadministration of olaparib with velpatasvir is necessary, due to the risk of increased olaparib-related adverse reactions and altered exposure of velpatasvir. Olaparib is a CYP2B6 inducer in vitro, and velpatasvir is a CYP2B6 substrate. Concomitant use may result in decreased velpatasvir exposure. Additionally, velpatasvir is a P-glycoprotein (P-gp) substrate / inhibitor and BCRP substrate. Olaparib is also an in vitro P-gp substrate / inhibitor and a BCRP inhibitor, although the clinical relevance of these findings is unknown.
Ombitasvir; Paritaprevir; 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. Concurrent administration of sofosbuvir with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of sofosbuvir. Ritonavir is an inhibitor of the breast cancer resistance protein (BCRP); dasabuvir and paritaprevir are substrates/inhibitors of BCRP, while sofosbuvir is a BCRP substrate. Caution and close monitoring are advised if these drugs are administered together.
Omeprazole: Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Omeprazole; Sodium Bicarbonate: Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of vel |
