Usage
Fluticasone Furoate + Umeclidinium + Vilanterol is prescribed for the maintenance treatment of:
- Chronic Obstructive Pulmonary Disease (COPD) in adults. This includes chronic bronchitis and emphysema. It helps improve lung function, manage symptoms like breathlessness and cough, and reduce the frequency of exacerbations.
- Asthma in adults. It is used as a maintenance therapy to control asthma symptoms and prevent attacks when other asthma medications haven’t been sufficient, or in severe cases requiring multiple medications.
Pharmacological Classification:
This medication is a combination of three active ingredients, each belonging to a different drug class:
- Fluticasone Furoate: Inhaled Corticosteroid (ICS)
- Umeclidinium: Long-acting Muscarinic Antagonist (LAMA) or anticholinergic
- Vilanterol: Long-acting Beta2-adrenergic Agonist (LABA)
Mechanism of Action:
- Fluticasone Furoate: Reduces airway inflammation by suppressing the immune response and decreasing the production of inflammatory mediators.
- Umeclidinium: Relaxes the smooth muscles around the airways by blocking the action of acetylcholine at muscarinic receptors, leading to bronchodilation.
- Vilanterol: Relaxes airway smooth muscle by stimulating beta2-adrenergic receptors, resulting in bronchodilation and improved airflow.
Alternate Names
- International Nonproprietary Name (INN): Fluticasone furoate/umeclidinium bromide/vilanterol
- Brand Name: Trelegy Ellipta, Elebrato Ellipta
How It Works
Pharmacodynamics:
The combined effect of the three components provides additive bronchodilation and anti-inflammatory action. Fluticasone furoate reduces airway inflammation, while umeclidinium and vilanterol relax airway smooth muscle, leading to improved lung function and symptom relief in COPD and asthma patients.
Pharmacokinetics:
- Absorption: All three drugs are administered via inhalation and are systemically absorbed to varying degrees.
- Metabolism:
- Fluticasone furoate and vilanterol are primarily metabolized by CYP3A4 enzymes in the liver.
- Umeclidinium is a substrate of CYP2D6.
- Elimination: Primarily eliminated through feces and to a lesser extent in urine.
Mode of Action:
- Fluticasone Furoate: Binds to glucocorticoid receptors in the cytoplasm, modulating gene transcription and reducing the production of inflammatory mediators.
- Umeclidinium: Competitively binds to muscarinic M3 receptors on airway smooth muscle, preventing bronchoconstriction.
- Vilanterol: Selectively stimulates beta2-adrenergic receptors on airway smooth muscle, activating intracellular pathways leading to smooth muscle relaxation.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation:
- Fluticasone furoate: Glucocorticoid receptor agonist.
- Umeclidinium: Muscarinic M3 receptor antagonist.
- Vilanterol: Beta2-adrenergic receptor agonist.
Elimination Pathways:
- Primarily fecal excretion, with minor renal excretion.
- Hepatic metabolism by CYP3A4 (fluticasone furoate and vilanterol) and CYP2D6 (umeclidinium).
Dosage
Standard Dosage
Adults:
- COPD: One inhalation of Trelegy Ellipta 100/62.5/25 mcg once daily.
- Asthma: One inhalation of Trelegy Ellipta 100/62.5/25 mcg or 200/62.5/25 mcg once daily, depending on disease severity and previous asthma therapy.
Children:
Use of Fluticasone Furoate + Umeclidinium + Vilanterol is not recommended in children under 18 years of age. Safety and efficacy have not been established in this population.
Special Cases:
- Elderly Patients: No dose adjustment is generally required.
- Patients with Renal Impairment: No dose adjustment is required.
- Patients with Hepatic Dysfunction: Use with caution in moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: Monitor patients with heart problems, high blood pressure, seizures, thyroid problems, diabetes, weak bones (osteoporosis), immune system problems, eye problems (glaucoma, cataracts), prostate or bladder problems.
Clinical Use Cases
Fluticasone Furoate + Umeclidinium + Vilanterol is not indicated for:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., acute bronchospasm)
A short-acting beta2-agonist (e.g., albuterol) should be used for acute bronchospasm or exacerbations.
Dosage Adjustments
Dosage adjustments are generally not required for elderly patients or those with renal impairment. However, caution is advised in patients with moderate to severe hepatic impairment.
Side Effects
Common Side Effects:
- Nasopharyngitis
- Headache
- Upper respiratory tract infection
- Cold or flu symptoms (runny or stuffy nose, sore throat, cough)
- Nausea, vomiting, stomach pain, constipation, diarrhea
- Joint pain
- Hoarse voice
- Back pain
- Changes in taste
- Oral candidiasis (thrush)
Rare but Serious Side Effects:
- Paradoxical bronchospasm
- Pneumonia
- Hypersensitivity reactions (angioedema, urticaria)
- Hyperglycemia
- Glaucoma, cataracts
- Cardiovascular effects (tachycardia, palpitations)
- Hypokalemia
- Immunosuppression
- Osteoporosis
- Adrenal suppression
Long-Term Effects:
- Increased risk of osteoporosis with prolonged corticosteroid use.
- Increased risk of glaucoma and cataracts.
- Adrenal suppression.
- Growth suppression in children (although this medication is not recommended for children).
Adverse Drug Reactions (ADR):
- Angioedema
- Severe bronchospasm
Contraindications
- Hypersensitivity to any of the components.
- Primary treatment of acute bronchospasm.
Drug Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): Increase the risk of systemic corticosteroid side effects. Monitor closely or avoid co-administration.
- Beta-blockers: May antagonize the bronchodilating effects of vilanterol.
- Other LABAs or LAMAs: Avoid concomitant use as it may potentiate adverse reactions.
- Diuretics (especially thiazide and loop diuretics): May increase the risk of hypokalemia.
- QTc prolonging drugs: Use with caution as vilanterol may also prolong the QTc interval.
Pregnancy and Breastfeeding
- Pregnancy: Insufficient data in humans. Use only if the potential benefit outweighs the potential risk to the fetus.
- Breastfeeding: It is unknown if the components are excreted in human milk. Consider the benefits of breastfeeding along with the mother’s clinical need and potential risks to the infant.
Drug Profile Summary
- Mechanism of Action: Combination of ICS, LAMA, and LABA providing additive bronchodilation and anti-inflammatory effects.
- Side Effects: Nasopharyngitis, headache, upper respiratory tract infection, paradoxical bronchospasm, pneumonia, hypersensitivity reactions.
- Contraindications: Hypersensitivity, primary treatment of acute bronchospasm.
- Drug Interactions: Strong CYP3A4 inhibitors, beta-blockers, other LABAs/LAMAs, diuretics, QTc prolonging drugs.
- Pregnancy & Breastfeeding: Insufficient data. Use with caution.
- Dosage: One inhalation once daily (100/62.5/25 mcg or 200/62.5/25 mcg for asthma).
- Monitoring Parameters: Lung function (FEV1), symptoms, blood glucose, potassium levels, eye exams (for glaucoma/cataracts).
Popular Combinations
This medication is itself a combination product, so additional combinations with other LABAs, LAMAs, or ICSs are generally avoided due to the potential for increased adverse effects. Short-acting beta2-agonists (e.g., albuterol) can be used as needed for acute bronchospasm.
Precautions
- General Precautions: Assess for pre-existing medical conditions, including heart problems, liver problems, diabetes, glaucoma, cataracts, and osteoporosis. Monitor for adverse reactions.
- Specific Populations: Use with caution in pregnant or breastfeeding women and in patients with moderate to severe hepatic impairment. Not recommended for children.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fluticasone Furoate + Umeclidinium + Vilanterol?
A: For COPD, one inhalation of 100/62.5/25 mcg once daily. For asthma, one inhalation of either 100/62.5/25 mcg or 200/62.5/25 mcg once daily, depending on disease severity and prior treatment.
Q2: Can this medication be used to treat acute asthma attacks?
A: No, this medication is for maintenance treatment and should not be used to relieve acute bronchospasm or asthma attacks. A rescue inhaler (short-acting beta2-agonist) should be used for these situations.
Q3: What are the most common side effects?
A: The most common side effects include nasopharyngitis, headache, upper respiratory tract infections, and cold or flu symptoms.
Q4: Are there any serious drug interactions I should be aware of?
A: Yes, strong CYP3A4 inhibitors can increase the risk of systemic corticosteroid side effects. Concomitant use of other LABAs or LAMAs may potentiate adverse effects.
Q5: Can this medication be used during pregnancy or breastfeeding?
A: There is limited data on the use of this medication during pregnancy and breastfeeding. Use only if the potential benefit outweighs the risk.
Q6: What should patients with liver problems do?
A: Patients with mild to moderate hepatic impairment can generally use this medication without dose adjustments. However, those with moderate to severe impairment should use it with caution and under close monitoring.
Q7: Can patients stop taking this medication abruptly?
A: No, patients should not discontinue this medication without consulting their doctor. Symptoms may recur upon sudden discontinuation.
Q8: How does this medication compare to other COPD or asthma treatments?
A: This medication combines three different mechanisms of action, offering comprehensive management of COPD and asthma. It may be particularly beneficial for patients not adequately controlled on other therapies.
Q9: What should I monitor in patients taking this medication?
A: Monitor lung function (FEV1), symptom control, blood glucose, potassium levels, and conduct regular eye exams to check for glaucoma and cataracts.
