Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein may increase the systemic exposure to indacaterol following oral inhalation, as it is a substrate of both the isoenzyme and efflux transporter. When a single 300 mcg dose of indacaterol inhalation powder was administered in combination with the potent dual CYP450 3A4/P-glycoprotein inhibitor, ketoconazole (200 mcg twice daily for 7 days), indacaterol peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3- and 1.9-fold, respectively. These changes probably reflect the impact of maximal combined inhibition. Similarly, verapamil 80 mg three times a day for 4 days increased indacaterol Cmax by 1.5-fold and AUC by 2-fold, while erythromycin 400 mg four times a day for 7 days increased indacaterol Cmax by 1.2-fold and AUC by 1.4-fold. Ritonavir 300 mg twice daily for 7.5 days had no effect on the Cmax of indacaterol, but increased its AUC by 1.7-fold. Indacaterol oral inhalation powder has been evaluated in clinical trials for up to one year at doses up to 600 mcg. No dosage adjustment is necessary at the 75 mcg dose when used with CYP450 3A4 and P-glycoprotein inhibitors.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.