Drug Interactions between ivosidenib and sofosbuvir / velpatasvir / voxilaprevir

MONITOR: Coadministration with ivosidenib may increase plasma concentrations of drugs that are substrates of P-glycoprotein (P-gp) and/or organic anion transporter 3 (OAT3). Based on in vitro studies, ivosidenib may decrease clearance via inhibition of P-gp and OAT3, resulting in increased plasma concentrations of agents that are substrates of these transporters. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Caution is advised if ivosidenib is used concomitantly with substrates of P-gp and/or OAT3. If coadministration is required, clinical and laboratory monitoring may be appropriate whenever ivosidenib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.

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.

MONITOR: Coadministration with ivosidenib may decrease plasma concentrations of drugs that are substrates of CYP450 2B6, 2C8, and/or 2C9. Based on in vitro studies, ivosidenib may increase clearance via induction of CYP450 2B6, 2C8, and 2C9, resulting in increased plasma concentrations of agents that are metabolized by these enzymes. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Caution is advised if ivosidenib is used concomitantly with substrates of CYP450 2B6, 2C8, and/or 2C9, particularly sensitive substrates or those with a narrow therapeutic range. If coadministration is required, clinical and laboratory monitoring may be appropriate whenever ivosidenib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.