Vilanterol trifenatate

This product is a compound preparation, and its active ingredients are fluticasone furoate, umeclidinium bromide and vilanterol triphenylacetate. Active ingredient: Fluticasone furoate Chemical name: (6,11,16,17)-6,9-difluoro-17-{[(fluoromethyl)thio]carbonyl}-11-hydroxy-16-methyl-3-oxoandrosta-1,4-diethylenetriamine-17-furoic acid methyl ester Chemical structure: Molecular formula: C27H29F3O6S Molecular weight: 538.58 Active ingredient: umeclidinium bromide Chemical name: 1-[2-(benzyloxy)ethyl]-4-(hydroxydiphenylmethyl)-1-nitrogen cation bicyclo[2.2.2]bromooctane Chemical structure: Molecular formula: C29H34NO2·Br Molecular weight: 508.5 Active ingredient: Vilanterol triphenylacetate Chemical name: Triphenylacetic acid-4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol Chemical structure: Molecular formula: C24H33Cl2NO5·C20H16O2 Molecular weight: 774.8 Excipients: lactose (C12H22O11·H2O), magnesium stearate.

Due to the low plasma concentrations achieved after inhaled administration, clinically significant drug interactions mediated by FF/UMEC/VI are not expected to occur at clinical doses. Interactions with Beta-Blockers Beta-2 adrenergic blockers may attenuate or antagonize the effects of beta-2 adrenergic agonists (e.g., VI). If a beta-blocker is necessary, a cardioselective beta-blocker should be considered, but concomitant use of non-selective and selective beta-blockers should be used with caution. Interactions with CYP3A4 Inhibitors Both FF and VI are rapidly cleared by extensive first-pass metabolism mediated by the CYP3A4 enzyme. Caution should be exercised when coadministering with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, cobicistat-containing products) as systemic exposure of FF and VI may be increased, leading to an increased potential for adverse reactions. Coadministration should be avoided unless the benefit outweighs the increased risk of adverse reactions from systemic corticosteroids, in which case patients should be monitored for systemic corticosteroid adverse reactions. A repeat-dose study was conducted in healthy subjects with FF/VI (200 μg/25 μg) and ketoconazole (400 mg; a strong CYP3A4 inhibitor). Coadministration increased the mean 0-24 hour area under the plasma concentration-time curve (AUC(0-24)) and peak plasma concentration (Cmax) of FF by 36% and 33%, respectively. Increased FF exposure decreased 0-24 hour weighted mean serum cortisol by 27%. Coadministration increased the mean AUC(0-t) and Cmax of VI by 65% and 22%, respectively. Increased VI exposure did not result in β2-agonist-related systemic effects on heart rate or potassium. Interactions with CYP2D6 Inhibitors/CYP2D6 PolymorphismsUMEC is a substrate of cytochrome P4502D6 (CYP2D6). The steady-state pharmacokinetics of UMEC were evaluated in healthy volunteers lacking CYP2D6 (poor metabolizers). At doses 8 times the therapeutic dose, no effects on UMECAUC or Cmax were observed. At dose increases up to 16-fold, an approximately 1.3-fold increase in UMECAUC was observed with no effect on UMECCmax. Based on the magnitude of these changes, no clinically relevant drug interactions are expected to occur when FF/UMEC/VI is co-administered with CYF2D6 inhibitors in patients with genetic defects in CYP2D6 activity (poor metabolizers) (see [Pharmacokinetics]). Interactions with P-glycoprotein inhibitors FF, UMEC, and VI are substrates of the P-glycoprotein transporter (P-gp). The effects of the moderate P-gp inhibitor verapamil (240 mg once daily) on the steady-state pharmacokinetics of UMEC and VI were evaluated in healthy volunteers. No effects of verapamil on UMEC and VICmax were observed. An approximately 1.4-fold increase in UMECAUC was observed with no effect on VIAUC. Based on the magnitude of these changes, no clinically relevant drug interactions are expected to occur when FF/UMEC/VI is co-administered with P-gp inhibitors. Clinical pharmacology studies of specific P-gp inhibitor interactions with FF have not been conducted. Other Long-Acting Antimuscarinics and Long-Acting β2-Adrenergic Agonists Coadministration of vilanterol with other long-acting muscarinic antagonists (LAMAs) or long-acting β2-adrenergic agonists (LABAs) has not been studied and is not recommended because of the potential for enhanced adverse reactions (see Adverse Reactions and Overdosage). Similar to interactions with monoamine oxidase inhibitors and tricyclic antidepressants and other β2-agonists, vilanterol should be used with extreme caution in patients receiving monoamine oxidase inhibitors, tricyclic antidepressants, or medications known to prolong the QTc interval and within 2 weeks of discontinuation of such medications because such medications may enhance the cardiovascular effects of adrenergic agonists. Medications known to prolong the QTc interval increase the risk of ventricular arrhythmias. Additive effects may occur when anticholinergics are coadministered with anticholinergics. Therefore, the concomitant use of this product with other drugs containing anticholinergic agents should be avoided to avoid increased anticholinergic adverse reactions (see [Precautions]). Hypokalemia: Concomitant hypokalemia treatment with methylxanthine derivatives, steroids, or non-potassium-sparing diuretics may enhance the hypokalemic effect of β2-adrenergic agonists, so caution should be exercised (see [Precautions]).

This product is a compound preparation, and its active ingredients are umeclidinium bromide and vilanterol triphenylacetate. Active ingredient: umeclidinium bromide Chemical name: 1-[2-(benzyloxy)ethyl]-4-(hydroxydiphenylmethyl)-1-nitrogen cation bicyclo[2.2.2]bromooctane Molecular formula: C29H34NO2·Br Molecular weight: 508.5 Active ingredient: vilanterol triphenylacetate Chemical name: triphenylacetic acid-4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol Molecular formula: C24H33Cl2NO5·C20H16O2 Molecular weight: 774.8 Excipients: lactose (C12H22O11·H2O), magnesium stearate.

β-adrenergic receptor blockers Medicinal products containing β-adrenergic receptor blockers may reduce or antagonize the effects of β2-adrenergic receptor agonists (e.g., vilanterol). Concomitant use of non-selective or selective β-adrenergic receptor blockers should be avoided unless there is a strong rationale for co-administration. Based on metabolic and transporter interactions Vilanterol is a substrate of cytochrome P4503A4 (CYP3A4). Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir, telithromycin) may inhibit the metabolism of vilanterol and increase its systemic exposure. Co-administration of ketoconazole (400 mg) in healthy subjects increased the mean AUC(0-t) and Cmax of vilanterol by 65% and 22%, respectively. The increase in vilanterol exposure was not associated with increases in systemic effects on heart rate, serum potassium, or QT interval (corrected by Fridericia's method) associated with β-adrenergic receptor agonists. Caution should be exercised when umeclidinium/vilanterol is coadministered with ketoconazole or other known strong CYP3A4 inhibitors due to the potential for increased systemic exposure of vilanterol, which may increase the potential for adverse reactions. Verapamil, a moderate CYP3A4 inhibitor, did not significantly affect the pharmacokinetics of vilanterol. Umeclidinium is a substrate for cytochrome P4502D6 (CYP2D6). The steady-state pharmacokinetics of umeclidinium were evaluated in healthy subjects deficient in CYP2D6 (poor metabolizers). At the 4-fold dose level, no effect on the AUC or Cmax of umeclidinium was observed. At the 8-fold dose level, an approximately 1.3-fold increase in the AUC of umeclidinium was observed with no effect on the Cmax of umeclidinium. Based on the magnitude of these data, no clinically relevant drug interactions are expected when umeclidinium/vilanterol is coadministered with CYP2D6 inhibitors or when umeclidinium/vilanterol is administered to patients genetically deficient in CYP2D6 activity (poor metabolizers). Both umeclidinium and vilanterol are substrates of the P-glycoprotein transporter (P-gp). The effect of the moderate P-gp inhibitor verapamil (240 mg once daily) on the steady-state pharmacokinetics of umeclidinium and vilanterol was evaluated in healthy subjects. No effect of verapamil on the Cmax of umeclidinium or vilanterol was observed. An approximately 1.4-fold increase in the AUC of umeclidinium was observed, with no effect on the AUC of vilanterol. Based on the magnitude of these data, no clinically relevant drug interactions are expected when umeclidinium/vilanterol is coadministered with P-gp inhibitors. Other antimuscarinic or sympathomimetic drugs have not been studied and coadministration of umeclidinium/vilanterol with other long-acting muscarinic antagonists, long-acting β2-adrenergic agonists, or formulations containing one of these agents is not recommended due to the potential for increased adverse reactions known to occur with inhaled muscarinic receptor antagonists or β2-adrenergic receptor agonists (see [Precautions] and [Overdosage]). Hypokalemia Co-administration of methylxanthine derivatives, steroids, or non-potassium sparing diuretics to treat hypokalemia may enhance the potential hypokalemic effects of β2-adrenergic receptor agonists and should be used with caution (see [Precautions]). Other therapeutic drugs for COPD Although formal in vivo drug interaction studies have not been conducted, umeclidinium/vilanterol has been used in combination with other COPD drugs (including short-acting sympathomimetic bronchodilators) and inhaled corticosteroids without clinical evidence of drug interactions.