Drug Interaction Report

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the systemic exposure to vilanterol following oral inhalation, as it is primarily metabolized by the isoenzyme. The interaction has been studied with fluticasone-vilanterol and ketoconazole. When fluticasone-vilanterol (200 mcg-25 mcg once daily for 7 days) was coadministered with ketoconazole (400 once daily for 11 days) in healthy subjects, fluticasone and vilanterol systemic exposure (AUC) were 36% and 65% higher, respectively, compared to coadministration with placebo. The increase in fluticasone exposure was associated with a 27% reduction in 24-hour weighted mean serum cortisol, whereas the increase in vilanterol exposure was not associated with an increase in beta-2 adrenergic systemic effects on heart rate or blood potassium.

MANAGEMENT: Due to the risk of cardiovascular adverse effects such as increases in pulse rate and blood pressure and ECG changes such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression, caution is recommended when medications containing vilanterol are coadministered with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics. An increased risk of systemic corticosteroid effects should also be considered when fluticasone-vilanterol is used.

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.