Viltica-U

Chronic Obstructive Pulmonary Disease (COPD):

• Indicated for the long-term, once-daily maintenance treatment of airflow obstruction in patients with moderate to very severe COPD.
• Reduces exacerbations in patients with a history of COPD exacerbations despite dual therapy with ICS/LABA or LAMA/LABA.

Asthma (Adults):

• Indicated as a once-daily maintenance treatment in adults (≥18 years) with asthma not adequately controlled with inhaled corticosteroid and long-acting beta2-agonist combination therapy.

Clinically Accepted (Off-label) Use:

• Asthma-COPD Overlap (ACO): In select adult patients with overlapping features of asthma and COPD, when triple therapy is justified by disease severity and exacerbation history.

Dosage Form:

• Inhalation powder via Ellipta inhaler.

Usual Adult Dose (COPD and Asthma):

• One inhalation once daily, containing:
• Umeclidinium Bromide 62.5 mcg
• Vilanterol Trifenatate 25 mcg
• Fluticasone Furoate 100 mcg or 200 mcg
• Administer at the same time each day, with or without food.

Pediatric Use:

• Not indicated in patients under 18 years.

Geriatric Use:

• No dosage adjustment required. Clinical studies show similar safety and efficacy in elderly patients.

Renal Impairment:

• No dosage adjustment needed.

Hepatic Impairment:

• Mild to moderate: No adjustment required.
• Severe: Use with caution due to limited data.

Important Administration Instructions:

• For oral inhalation only.
• Do not shake the inhaler.
• Rinse mouth with water (without swallowing) after each dose to reduce the risk of oropharyngeal candidiasis.
• Do not use more than one inhalation in 24 hours.

This is a triple-combination inhaler comprising:

• Umeclidinium Bromide: A LAMA that blocks muscarinic (M3) receptors in airway smooth muscle, preventing acetylcholine-induced bronchoconstriction.
• Vilanterol Trifenatate: A LABA that activates β2-adrenergic receptors, relaxing bronchial smooth muscle through increased cyclic AMP.
• Fluticasone Furoate: An ICS that binds to glucocorticoid receptors, suppressing inflammatory gene expression and reducing airway inflammation.

The combination offers bronchodilation from two different mechanisms (LAMA + LABA) and inflammation control from the corticosteroid component, improving lung function and preventing exacerbations.

Absorption:

• Rapid systemic absorption after inhalation.
• Time to peak plasma concentration:
• Umeclidinium: ~5–15 minutes
• Vilanterol: ~10 minutes
• Fluticasone Furoate: ~30 minutes

Bioavailability (oral inhalation):

• Fluticasone Furoate: ~15%
• Vilanterol: ~27%
• Umeclidinium: ~13%

Distribution:

• High volume of distribution, indicating extensive tissue penetration.
• Fluticasone: ~661 L
• Vilanterol: ~165 L
• Umeclidinium: ~86 L

Metabolism:

• Fluticasone Furoate: Mainly by CYP3A4 to inactive metabolites.
• Vilanterol: By CYP3A4 and further glucuronidation.
• Umeclidinium: By CYP2D6 and ester hydrolysis.

Elimination Half-Life:

• Fluticasone: ~24 hours
• Vilanterol: ~21 hours
• Umeclidinium: ~11 hours

Excretion:

• Primarily fecal; <2% renal excretion for all components.

Pregnancy:

• Use only if clearly needed. Limited human data; animal studies show potential adverse effects at high doses.
• Benefits must outweigh risks in pregnant women.

Lactation:

• Unknown if excreted in human milk.
• The potential for systemic corticosteroid or beta-agonist exposure in infants should be considered.
• Use caution; consider risk-benefit analysis.

Fertility:

• No human data. Animal studies did not indicate harmful effects on fertility.

• Primary Class: Triple combination inhalation therapy
• Components:
• LAMA: Umeclidinium
• LABA: Vilanterol
• ICS: Fluticasone Furoate
• Use: Maintenance treatment for COPD and moderate-to-severe asthma

• Hypersensitivity to any of the components or excipients (including lactose or milk proteins)
• Primary treatment of acute bronchospasm
• Status asthmaticus
• Co-administration with other LABA or LAMA agents

• Not for acute symptom relief.
• Asthma-related deaths: LABA monotherapy risk eliminated by combining with ICS.
• Paradoxical bronchospasm: Discontinue immediately if it occurs.
• Increased pneumonia risk in COPD patients, especially the elderly.
• Systemic corticosteroid effects: Adrenal suppression, decreased bone density, and immunosuppression with high doses.
• Cardiovascular risks: Use cautiously in patients with arrhythmia, ischemic heart disease, or hypertension.
• Narrow-angle glaucoma and urinary retention: May worsen these conditions; use with caution.

Common Side Effects:

• Headache
• Cough
• Nasopharyngitis
• Upper respiratory tract infection
• Oropharyngeal candidiasis
• Dysphonia
• Dry mouth

Serious Side Effects:

• Pneumonia (especially in COPD)
• Paradoxical bronchospasm
• Hypokalemia
• QT prolongation
• Hypersensitivity reactions (rash, angioedema, anaphylaxis)
• Adrenal suppression with long-term high-dose use

Long-term ICS risks:

• Osteoporosis
• Cataracts
• Growth suppression (theoretical in younger populations)

• CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): May increase systemic exposure to fluticasone and vilanterol → higher risk of systemic corticosteroid effects and QT prolongation.
• Beta-blockers: May antagonize the effect of vilanterol → bronchospasm risk.
• MAO inhibitors & tricyclic antidepressants: May enhance cardiovascular effects of vilanterol.
• Diuretics (non-K+ sparing): Enhanced risk of hypokalemia.

Recommendation:

• Avoid co-administration with other LABAs, LAMAs, or corticosteroids unless clinically necessary.

• GOLD 2024 (COPD): Recommends triple therapy (ICS + LABA + LAMA) for patients with frequent exacerbations or elevated eosinophil counts despite dual therapy.
• GINA 2024 (Asthma): Triple therapy endorsed in adults with moderate to severe asthma not controlled with ICS/LABA alone.
• FDA (latest labeling): Highlights pneumonia risk in COPD, especially with ICS-containing inhalers; advises appropriate monitoring.

• Temperature: Store below 25°C (77°F).
• Moisture: Keep in original blister until use.
• Handling:
• Keep inhaler dry and tightly closed when not in use.
• Do not wash or immerse inhaler in water.
• In-use shelf life:
• Discard 6 weeks after opening or when dose counter reads “0.”
• Do not freeze or refrigerate.