Vilanterol Trifenatate

Bronchodilator; a relatively selective, long-acting β2-adrenergic agonist.1 2 3 4 5 6 16 18

Substrate of CYP3A4 and P-glycoprotein (P-gp).1 7 16

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes and/or the P-glycoprotein Transport System

Potent inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased vilanterol concentrations).1 7 16 Use caution with long-term concomitant therapy.1 16

Potent inhibitors of P-gp: Clinically important effects on pharmacokinetics unlikely.1 16

Drugs that Prolong the QT Interval

Potential pharmacologic interaction (increased risk of ventricular arrhythmias and possible potentiation of vilanterol effects on cardiovascular system).1 16 Use extreme caution during concomitant therapy or within 2 weeks of discontinuance of such agents.1 16

Specific Drugs

Absorption

Bioavailability

Rapidly absorbed following oral inhalation;15 absolute bioavailability of vilanterol in fixed combination with fluticasone is approximately 27%, principally due to absorption of drug delivered to the lungs.1

Oral bioavailability of the swallowed portion of an inhaled dose is low (<2% for vilanterol in fixed combination with fluticasone) because of extensive first-pass metabolism.1 6 7 16

Peak plasma concentrations reached within 5–15 minutes following oral inhalation.1 15 16

Steady-state concentrations achieved after 6 days of once-daily dosing of vilanterol/fluticasone fixed-combination therapy and within 14 days of once-daily dosing of vilanterol/umeclidinium fixed-combination therapy.1 16

Onset

Vilanterol/fluticasone in fixed combination: Median time to onset (defined as a 100-mL increase from baseline in FEV1) 16 minutes.1

Vilanterol/umeclidinium in fixed combination: Median time to onset 27 minutes.16

Duration

Bronchodilation generally persists for 24 hours.4 5 6

Special Populations

Vilanterol/fluticasone in fixed combination: No clinically important changes in peak concentrations or AUC of vilanterol, but increased exposure of fluticasone observed in patients with mild, moderate, or severe hepatic impairment.1 (See Hepatic Impairment under Cautions.)

Vilanterol/umeclidinium in fixed combination: No clinically important changes in peak concentrations or AUC of vilanterol or umeclidinium in patients with moderate hepatic impairment.16 (See Hepatic Impairment under Cautions.)

Distribution

Extent

Not known whether distributed into human milk.1 16

Plasma Protein Binding

Approximately 94%.1 16

Elimination

Metabolism

Extensively metabolized, mainly by CYP3A4.1 6 16

Elimination Route

Excreted mainly as metabolites in urine (70%) and feces (30%) following oral administration.1 6 16

Half-life

Effective half-life for vilanterol in fixed combination with fluticasone: 21.3 hours following oral inhalation of multiple doses in patients with COPD.1

Effective half-life of vilanterol in fixed combination with umeclidinium: 11–19 hours following oral inhalation of multiple doses in healthy individuals.16 19

Special Populations

No clinically important differences in pharmacokinetics based on age, race, or gender.1 16

Possible increased exposure in patients with severe renal impairment.1 16

• Synthetic sympathomimetic amine.1 2 3 4 5 6

• Relatively selective, long-acting β2-adrenergic agonist.1 2 3 4 5 6 16 18

• Functional selectivity of vilanterol in vitro similar to that of salmeterol; clinical importance unknown.1 5 16 18

• Increases concentrations of cyclic adenosine-3′,5′-monophosphate (cAMP), resulting in relaxation of bronchial smooth muscle.1 5 16 18

• Appears to inhibit release of mediators of immediate hypersensitivity from cells, especially mast cells.1 16 18

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.