Vilanterol Trifenatate + Umeclidinium Bromide

Approved Indications:

• Chronic Obstructive Pulmonary Disease (COPD):
  Indicated for long-term, once-daily maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema.
• Maintenance Bronchodilator Therapy:
  Used to reduce exacerbations and improve lung function in moderate to very severe COPD.

Important Off-label Use:

• Though not FDA-approved for asthma, this combination may be used in select cases under specialist supervision, especially in patients with COPD-asthma overlap.

Adults (including elderly):

• Recommended Dose:
  One inhalation once daily via a dry powder inhaler (e.g., Ellipta), delivering 62.5 mcg of umeclidinium and 25 mcg of vilanterol.
• Route: Inhalation only
• Frequency: Once daily, at the same time each day
• Onset of Action: Within 5–15 minutes
• Duration of Action: Up to 24 hours

Pediatric Use:

• Not approved or recommended for children and adolescents under 18 years.

Renal Impairment:

• No dose adjustment required.

Hepatic Impairment:

• Mild to moderate: No adjustment needed.
• Severe: Use with caution; clinical data limited.

Administration Instructions:

• Do not shake the inhaler.
• Do not use more than once daily.
• Rinse mouth after inhalation to reduce the risk of oropharyngeal irritation or infection.

Vilanterol is a long-acting beta-2 adrenergic agonist (LABA) that stimulates β2-adrenergic receptors in the airway smooth muscle, leading to relaxation and bronchodilation. Umeclidinium is a long-acting muscarinic antagonist (LAMA) that blocks the action of acetylcholine on M3 receptors in bronchial smooth muscle, thereby preventing bronchoconstriction. The combination provides dual bronchodilation through complementary mechanisms, resulting in enhanced airway patency and symptom relief in COPD.

• Absorption:
  Rapidly absorbed after inhalation; peak plasma concentrations reached within 5–15 minutes.
• Bioavailability:
  Vilanterol ~27%; Umeclidinium ~13%
• Distribution:
  Vilanterol has a large volume of distribution (~165 L). Umeclidinium binds moderately to plasma proteins (~89%).
• Metabolism:
  Vilanterol is metabolized mainly by CYP3A4 and undergoes O-dealkylation. Umeclidinium is primarily metabolized by hepatic CYP2D6 and via ester hydrolysis.
• Half-life:
  Vilanterol ~21 hours; Umeclidinium ~11 hours
• Excretion:
  Vilanterol: Mainly feces (~85%), urine (~6%)
  Umeclidinium: Primarily via feces (~58%), some in urine (~22%)

• Pregnancy:
  There is no FDA-assigned pregnancy category under the current labeling system. Animal studies have shown adverse effects at high doses. Use only if the potential benefit justifies the potential risk.
• Lactation:
  Unknown whether vilanterol or umeclidinium is excreted in human milk. Use caution; consider discontinuing breastfeeding or the drug depending on the clinical importance.
• Caution is advised due to limited human data.

• Primary Class: Long-acting Bronchodilator Combination
• Subclass:
• LAMA/LABA Combination Inhaler
• Umeclidinium: Long-acting muscarinic antagonist (LAMA)
• Vilanterol: Long-acting beta-2 agonist (LABA)

• Known hypersensitivity to vilanterol, umeclidinium, or any excipients
• Severe hypersensitivity reactions including anaphylaxis, angioedema, or urticaria
• Monotherapy in asthma without inhaled corticosteroids (increased risk of asthma-related death)
• Severe milk protein allergy (product may contain lactose)

• Asthma-Related Death: LABAs should not be used without inhaled corticosteroids in asthma.
• Paradoxical Bronchospasm: Discontinue immediately if it occurs.
• Narrow-Angle Glaucoma & Urinary Retention: Use cautiously in susceptible individuals.
• Cardiovascular Effects: Use with caution in patients with cardiac arrhythmias, hypertension, or heart failure.
• Hypokalemia and Hyperglycemia: May worsen metabolic profiles, particularly in diabetics or those on corticosteroids.
• Monitoring: Assess lung function periodically. Monitor for signs of glaucoma, urinary retention, or cardiovascular events.

Common Side Effects:

• Respiratory: Cough, nasopharyngitis, upper respiratory tract infection, pharyngitis
• Gastrointestinal: Dry mouth, constipation
• Neurological: Headache, dizziness
• Musculoskeletal: Arthralgia, back pain

Serious Side Effects:

• Hypersensitivity reactions (including rash, angioedema)
• Paradoxical bronchospasm
• Atrial fibrillation or other arrhythmias
• Glaucoma exacerbation
• Urinary retention

Rare Side Effects:

• Hypokalemia
• Hyperglycemia
• Anaphylactic reactions

• Beta-blockers (especially non-selective): May reduce bronchodilator effect of vilanterol.
• CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): Increase systemic exposure to vilanterol → risk of QT prolongation or arrhythmias.
• Anticholinergics: Additive effects → risk of urinary retention or glaucoma.
• Diuretics: Increased risk of hypokalemia.
• MAOIs & Tricyclic Antidepressants: Potential for enhanced cardiovascular effects.

Enzyme Systems:

• Vilanterol: Primarily metabolized by CYP3A4
• Umeclidinium: Metabolized via CYP2D6 and ester hydrolysis

• Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024:
  Recommends LAMA/LABA combinations like umeclidinium/vilanterol as first-line maintenance therapy for Group B and Group D COPD patients.
• FDA & EMA Updates:
  No recent major label changes as of mid-2025; safety remains consistent with previous assessments. Monitoring of cardiovascular effects and hypersensitivity continues as standard.

• Temperature: Store below 25°C (77°F)
• Humidity: Store in a dry place; avoid high humidity
• Light Protection: Keep in the original packaging to protect from light
• Handling: Do not open inhaler until ready to use.
• Discarding: Discard inhaler 6 weeks after opening or when the counter reads “0,” whichever comes first.
• Do not refrigerate or freeze.