Drug Interactions between echinacea and sofosbuvir / velpatasvir / voxilaprevir

MONITOR: Coadministration with echinacea may alter the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 3A4. Echinacea appears to inhibit intestinal CYP450 3A4, which would lead to an increase in oral midazolam (a sensitive 3A4 substrate) bioavailability; however, plasma levels of midazolam following oral administration do not appear to be affected by echinacea. In contrast, it appears that echinacea may also induce hepatic CYP450 3A4; thereby increasing the hepatic clearance of drugs that are substrates of CYP450 3A4. According to reports, echinacea may increase the hepatic clearance of intravenous (IV) midazolam by 34% and decrease the area under the concentration-time curve (AUC) and half-life of IV midazolam by 20% and 42%, respectively.

MANAGEMENT: In general, patients should be advised to consult their healthcare provider before using any herbal or alternative medicines. If echinacea is prescribed with a drug that is a CYP450 3A4 substrate, the possibility of an altered (increased or decreased) therapeutic response should be considered. Patients should be monitored more closely following the addition or withdrawal of echinacea and the dosage of the CYP450 3A4 substrate adjusted as necessary.

MONITOR: Coadministration with inhibitors of organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations of voxilaprevir, which is a substrate of the hepatic uptake transporters. When a single 100 mg dose of voxilaprevir was administered with a single 600 mg dose of the potent OATP 1B1/1B3 inhibitor cyclosporine (n=24), mean voxilaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 19.0- and 9.4-fold, respectively. Inhibition of P-glycoprotein (P-gp)- and breast cancer resistance protein (BCRP)-mediated intestinal transport and CYP450 3A4-mediated metabolism of voxilaprevir may also contribute to the overall interaction with cyclosporine. The safety of such high levels of voxilaprevir has not been established.

MANAGEMENT: Caution and monitoring are advised when voxilaprevir is used with OATP 1B1 or 1B3 inhibitors.