Drug Interactions between abametapir topical and sofosbuvir / velpatasvir / voxilaprevir

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.

GENERALLY AVOID: Based on in vitro inhibition data, a single topical application of abametapir lotion may increase plasma concentrations of drugs that are substrates of CYP450 3A4, CYP450 2B6, and CYP450 1A2 isoenzymes and increase their systemic concentrations. The proposed mechanism is high and prolonged systemic exposure to the metabolite abametapir carboxyl, which has been shown to be an in vitro inhibitor of CYP450 3A4, CYP450 2B6, and CYP450 1A2. The mean half-life of abametapir carboxyl in adults is estimated to be 71 hours or longer.

MANAGEMENT: Use of CYP450 3A4, CYP450 2B6, and CYP450 1A2 substrates should generally be avoided within 2 weeks after topical application of abametapir lotion. If this is not feasible, the manufacturer recommends avoiding use of abametapir lotion. If abametapir is used, monitor for increased toxicity of the CYP450 3A4, CYP450 2B6, and/or CYP450 1A2 substrate.