Drug Interactions between afatinib and sofosbuvir / velpatasvir / voxilaprevir

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of afatinib, which is a substrate of the efflux transporter. In study subjects, oral administration of the P-gp inhibitor ritonavir (200 mg twice daily) one hour before afatinib dosing resulted in a 48% increase in afatinib systemic exposure. There was no change in afatinib exposure when ritonavir was administered simultaneously with, or 6 hours after, the afatinib dose.

MANAGEMENT: Caution is advised if afatinib is used in combination with P-gp inhibitors. Patients should be monitored for potentially increased adverse effects such as diarrhea, which may lead to dehydration with or without renal impairment; cutaneous reactions including rash, erythema, and bullous, blistering, or exfoliating lesions; interstitial lung disease such as lung infiltration, pneumonitis, acute respiratory distress syndrome, and allergic alveolitis; hepatotoxicity, which may be life-threatening or fatal; keratitis characterized by acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, red eye, and/or ulceration; and left ventricular dysfunction. The manufacturer recommends reducing the daily dose of afatinib by 10 mg if not tolerated. The previous dose may be resumed after discontinuation of the P-gp inhibitor as tolerated.

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ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of afatinib, which is a substrate of the efflux transporter. In study subjects, oral administration of the P-gp inhibitor ritonavir (200 mg twice daily) one hour before afatinib dosing resulted in a 48% increase in afatinib systemic exposure. There was no change in afatinib exposure when ritonavir was administered simultaneously with, or 6 hours after, the afatinib dose.

MANAGEMENT: Caution is advised if afatinib is used in combination with P-gp inhibitors. Patients should be monitored for potentially increased adverse effects such as diarrhea, which may lead to dehydration with or without renal impairment; cutaneous reactions including rash, erythema, and bullous, blistering, or exfoliating lesions; interstitial lung disease such as lung infiltration, pneumonitis, acute respiratory distress syndrome, and allergic alveolitis; hepatotoxicity, which may be life-threatening or fatal; keratitis characterized by acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, red eye, and/or ulceration; and left ventricular dysfunction. The manufacturer recommends reducing the daily dose of afatinib by 10 mg if not tolerated. The previous dose may be resumed after discontinuation of the P-gp inhibitor as tolerated.

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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.

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