Drug Interactions between abrocitinib and sofosbuvir / velpatasvir / voxilaprevir

MONITOR: Coadministration with abrocitinib may increase the plasma concentrations of drugs that are substrates of P-glycoprotein (P-gp), an efflux transporter inhibited in vitro by abrocitinib. Concomitant administration of dabigatran etexilate, a P-gp substrate, and abrocitinib (200 mg single dose) increased the dabigatran peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 40% and 53%, respectively. The effect of abrocitinib on pharmacokinetics of other P-gp substrates has not been evaluated.

MANAGEMENT: Caution is advised if abrocitinib is coadministered with P-gp substrates, particularly sensitive substrates or those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever abrocitinib is added to or withdrawn from therapy.

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.