Fluticasone Furoate + Glycopyrronium + Vilanterol

Usage

• Medical Conditions: This triple therapy is prescribed for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). It is also indicated for the maintenance treatment of asthma in patients aged 18 years and older. It is not for the relief of acute bronchospasms.
• Pharmacological Classification: This is a combination product containing:
  • Fluticasone furoate: Inhaled corticosteroid (ICS)
  • Glycopyrronium: Long-acting muscarinic antagonist (LAMA)
  • Vilanterol: Long-acting beta2-agonist (LABA)
• Mechanism of Action: This combination medication works by reducing inflammation, relaxing airway muscles, and improving airflow to the lungs. Fluticasone furoate reduces inflammation in the airways, glycopyrronium blocks the bronchoconstricting effects of acetylcholine, and vilanterol stimulates beta2-adrenergic receptors, leading to bronchodilation.

Alternate Names

• There is no single alternate generic name for this specific combination. The individual components may be referred to by their respective generic names.
• Brand Name: Trelegy Ellipta

How It Works

• Pharmacodynamics: Fluticasone furoate exerts its anti-inflammatory effect by binding to glucocorticoid receptors in the airways, reducing the production of inflammatory mediators. Glycopyrronium acts as a competitive antagonist at muscarinic M3 receptors, leading to bronchodilation. Vilanterol stimulates beta2-adrenergic receptors, resulting in relaxation of airway smooth muscle and bronchodilation.
• Pharmacokinetics:
  • Absorption: Each drug component is absorbed through the lungs.
  • Metabolism: Fluticasone furoate is primarily metabolized by CYP3A4. Glycopyrronium and vilanterol are also metabolized, although to a lesser extent.
  • Elimination: The drugs and their metabolites are primarily eliminated through feces and, to a lesser extent, urine.
• Mode of Action: The combined action of these drugs provides synergistic bronchodilation and anti-inflammatory effects.

Dosage

Standard Dosage

Adults:

• One inhalation (containing fluticasone furoate 100 mcg/glycopyrronium 62.5 mcg/vilanterol 25 mcg or fluticasone furoate 200 mcg/glycopyrronium 62.5 mcg/vilanterol 25 mcg) once daily. The 100 mcg strength is indicated for COPD and the 200 mcg strength is typically used for those with more severe asthma. Do not exceed one inhalation per day.

Children:

• Not recommended for use in children under 18 years of age.

Special Cases:

• Elderly Patients: No dosage adjustment is necessary.
• Patients with Renal Impairment: No dosage adjustment is necessary.
• Patients with Hepatic Dysfunction: No dose adjustment is necessary for mild to moderate impairment. Use with caution in patients with severe hepatic impairment.
• Patients with Comorbid Conditions: Monitor patients with cardiovascular disease, diabetes, hyperthyroidism, or a history of seizures.

Clinical Use Cases

• Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, Emergency Situations: This medication is not indicated for acute management in these settings. It is intended for long-term maintenance therapy of COPD and asthma.

Dosage Adjustments

• Dose adjustments are not typically required based on age, renal function, or mild to moderate hepatic impairment. For patients with severe hepatic impairment, use with caution. For those with poorly controlled asthma, dosage may be increased from 100 mcg to 200 mcg once daily.

Side Effects

Common Side Effects

• Headache, nasopharyngitis, upper respiratory tract infection, back pain, oropharyngeal pain, sinusitis, pneumonia, cough, dry/irritated throat, hoarseness.

Rare but Serious Side Effects

• Paradoxical bronchospasm, hypersensitivity reactions (including urticaria, angioedema, and anaphylaxis), QT prolongation, hyperglycemia, pneumonia, adrenal suppression, immunosuppression, osteoporosis, glaucoma, cataracts.

Long-Term Effects

• With prolonged use, potential risks include decreased bone mineral density, growth retardation in children (though this formulation isn’t recommended for children), and adrenal suppression.

Adverse Drug Reactions (ADR)

• Any signs of hypersensitivity require immediate intervention. Paradoxical bronchospasm, severe cardiovascular events, and serious infections should be addressed urgently.

Contraindications

• Hypersensitivity to any of the components, including milk proteins. It should not be used in patients with a primary diagnosis of status asthmaticus or other acute, severe exacerbations of COPD or asthma.

Drug Interactions

• Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) may increase fluticasone systemic exposure.
• Beta-blockers (e.g., propranolol) may antagonize the bronchodilatory effects of vilanterol.
• Anticholinergics (e.g., ipratropium) may have additive effects with glycopyrronium.
• Other long-acting beta2-agonists should be avoided.
• Monitor potassium levels when used with diuretics like hydrochlorothiazide.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: While there is no established FDA pregnancy category for this specific combination product, it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have shown teratogenic effects with individual components.
• Breastfeeding: It is unknown if the components are excreted in breast milk. Consult with a physician to weigh risks and benefits.

Drug Profile Summary

• Mechanism of Action: Combined anti-inflammatory (ICS), bronchodilator (LAMA), and bronchodilator (LABA) action.
• Side Effects: Common: Headache, nasopharyngitis, URI. Serious: Paradoxical bronchospasm, angioedema, QT prolongation, hyperglycemia.
• Contraindications: Hypersensitivity, acute asthma exacerbations, severe milk protein allergy.
• Drug Interactions: Strong CYP3A4 inhibitors, beta-blockers, anticholinergics, other LABAs.
• Pregnancy & Breastfeeding: Use with caution in pregnancy only if benefits outweigh risks; unknown if excreted in breast milk.
• Dosage: 1 inhalation once daily; not for use in children under 18.
• Monitoring Parameters: Lung function, blood glucose, potassium levels, eye exams (for long-term use), bone density (for long-term use), signs of adrenal insufficiency (with long-term use).

Popular Combinations

• This medication is itself a combination product and not typically combined with other long-term maintenance medications for asthma or COPD. Short-acting beta2-agonists (SABAs) like albuterol may be used as needed for acute symptom relief.

Precautions

• General Precautions: Assess for hypersensitivity, underlying medical conditions (cardiovascular disease, diabetes, hyperthyroidism, glaucoma, osteoporosis), and potential drug interactions.
• Specific Populations: Use cautiously in pregnancy and during breastfeeding. Not recommended for children.
• Lifestyle Considerations: Advise patients on proper inhaler technique.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Fluticasone Furoate + Glycopyrronium + Vilanterol?

A: One inhalation once daily, either 100mcg/62.5mcg/25mcg for COPD or 200mcg/62.5mcg/25mcg for asthma. Do not exceed this dose.

Q2: Can this medication be used for acute asthma attacks?

A: No, it is not a rescue inhaler.

Q3: What are the common side effects?

A: Headache, nasopharyngitis, upper respiratory infections.

Q4: Are there any serious drug interactions?

A: Yes, with strong CYP3A4 inhibitors (like ketoconazole), beta-blockers, and other LABAs.

Q5: Can it be used in pregnant or breastfeeding women?

A: Only if absolutely necessary and the potential benefit outweighs the risk. It’s unknown if the components pass into breast milk.

Q6: Is it safe for children?

A: No, it’s not recommended for those under 18.

Q7: What should I monitor in patients taking this medication long-term?

A: Lung function, bone density, eye health, and adrenal function, as well as blood glucose and potassium levels.

Q8: What should a patient do if they miss a dose?

A: Inhale the missed dose as soon as remembered, unless it is close to the time for the next dose. Do not double the dose.

Q9: Can a patient use other inhalers with this medication?

A: Avoid other LABAs. Short-acting beta-agonists (SABAs) can be used as needed for acute symptom relief. Consult a physician about concomitant use of other inhaled medications.