Relvar Ellipta Drug Interactions

Clinically significant drug interactions mediated by fluticasone furoate/vilanterol at clinical doses are considered unlikely due to the low plasma concentrations achieved after inhaled dosing.
Interaction with beta-blockers: Beta₂-adrenergic blockers may weaken or antagonise the effect of beta₂-adrenergic agonists. Concurrent use of both non-selective and selective beta₂-adrenergic blockers should be avoided unless there are compelling reasons for their use.
Interaction with CYP3A4 inhibitors: Fluticasone furoate and vilanterol are both rapidly cleared by extensive first pass metabolism mediated by the liver enzyme CYP3A4.
Caution is advised when co-administering with strong CYP 3A4 inhibitors (e.g. ketoconazole, ritonavir) as there is potential for increased systemic exposure to both fluticasone furoate and vilanterol, and concomitant use should be avoided. A repeat dose CYP3A4 drug interaction study was performed in healthy subjects with the fluticasone furoate/vilanterol combination (200/25 micrograms) and the strong CYP3A4 inhibitor ketoconazole (400 mg). Co-administration increased mean fluticasone furoate AUC_(0-24) and C_max by 36% and 33%, respectively. The increase in fluticasone furoate exposure was associated with a 27% reduction in 0-24 hours weighted mean serum cortisol. Co-administration increased mean vilanterol AUC_(0-t) and C_max 65% and 22%, respectively. The increase in vilanterol exposure was not associated with an increase in beta₂-agonist related systemic effects on heart rate, blood potassium or QTcF interval.
Interaction with P-glycoprotein inhibitors: Fluticasone furoate and vilanterol are both substrates of P-glycoprotein (P-gp). A clinical pharmacology study in healthy subjects with co-administered vilanterol and the potent P-gp and moderate CYP3A4 inhibitor verapamil did not show any significant effect on the pharmacokinetics of vilanterol. Clinical pharmacology studies with a specific P-gp inhibitor and fluticasone furoate have not been conducted.
Sympathomimetic medicinal products: Concomitant administration of other sympathomimetic medicinal products (alone or as part of combination therapy) may potentiate the adverse reactions of fluticasone furoate/vilanterol. Relvar Ellipta should not be used in conjunction with other long-acting beta₂-adrenergic agonists or medicinal products containing long-acting beta₂-adrenergic agonists.
Paediatric population: Interaction studies have only been performed in adults.