r administration by 4 hours. 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.
Aprepitant, Fosaprepitant: Use caution when administering velpatasvir with aprepitant. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a substrate of CYP3A4. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and weak inducer. Plasma concentrations of another CYP3A4 substrate, midazolam, increased from 1.25-fold to 3.3-fold after administration of a 3 to 5-day oral aprepitant regimen; midazolam concentrations were subsequently decreased by 19% and 4% on days 8 and 15, respectively. However, as a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, IV fosaprepitant (single dose) is rapidly converted to aprepitant and shares some of the same drug interactions but it only weakly inhibits CYP3A4 for a duration of 2 days, increasing the midazolam AUC by approximately 1.8-fold on day 1 with no effect by day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. There is no evidence of CYP3A4 induction with fosaprepitant.
Armodafinil: Avoid coadministration of velpatasvir with armodafinil. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; armodafinil is an in vitro inducer of CYP3A4.
Aspirin, ASA; 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.
Atazanavir: Use caution when administering velpatasvir with atazanavir. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2C8 and CYP3A4 substrate; atazanavir is a potent inhibitor of CYP3A4 and a weak inhibitor of CYP2C8.
Atazanavir; Cobicistat: Caution is warranted when cobicistat is administered with sofosbuvir as there is a potential for elevated concentrations of sofosbuvir. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the transporters P-glycoprotein and breast cancer resistance protein (BCRP). Sofosbuvir is a substrate of P-gp and BCRP. According to the manufacturer, no dosage adjustments are required when sofosbuvir is administered concurrently with P-gp or BCRP inhibitors. Use caution when administering velpatasvir with atazanavir. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2C8 and CYP3A4 substrate; atazanavir is a potent inhibitor of CYP3A4 and a weak inhibitor o |
