Usage
- This triple therapy is prescribed for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults. It is not indicated for the relief of acute bronchospasm or for the treatment of asthma.
- Pharmacological Classification: This combination drug includes a corticosteroid (fluticasone), a long-acting β2-adrenergic agonist (formoterol), and a long-acting muscarinic antagonist (glycopyrrolate). It can be classified as an inhaled corticosteroid/long-acting beta-agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) combination.
- Mechanism of Action: Fluticasone reduces airway inflammation, formoterol relaxes and widens the airways, and glycopyrrolate further enhances bronchodilation by blocking muscarinic receptors, ultimately improving airflow and reducing COPD symptoms.
Alternate Names
- While the generic name is Fluticasone Propionate + Formoterol + Glycopyrrolate, there may be regional variations.
- Brand Names: There are several brand names for this combination product and/or the related double combinations marketed in some parts of the world, depending on dosages and device. Examples include Trelegy Ellipta, Airz FF and others (not an exclusive list).
How It Works
- Pharmacodynamics: Fluticasone, a corticosteroid, binds to glucocorticoid receptors in the lungs, reducing inflammation by suppressing the release of inflammatory mediators and inhibiting inflammatory cell activation. Formoterol, a LABA, stimulates β2-adrenergic receptors, leading to bronchodilation through relaxation of airway smooth muscle. Glycopyrrolate, a LAMA, blocks muscarinic receptors, particularly M3 receptors in the airways, causing bronchodilation and also reducing mucus secretion.
- Pharmacokinetics: The combination is administered via inhalation. Fluticasone is systemically absorbed through the lungs, but due to extensive first-pass metabolism, oral bioavailability is low. Formoterol is also absorbed from the lungs but has a longer duration of action than short-acting β2-agonists. Glycopyrrolate demonstrates low systemic absorption after inhalation and therefore negligible systemic anticholinergic effects.
- Mode of Action: At the molecular level, fluticasone modulates gene transcription, suppressing inflammatory pathways. Formoterol activates adenylate cyclase, increasing intracellular cyclic AMP, leading to smooth muscle relaxation. Glycopyrrolate competitively inhibits acetylcholine binding to muscarinic receptors, preventing bronchoconstriction and mucus secretion.
- Elimination: Fluticasone is primarily metabolized by CYP3A4 enzymes and excreted in the feces. Formoterol is mainly metabolized by direct glucuronidation and excreted primarily in the urine. Glycopyrrolate is also primarily excreted unchanged in the urine.
Dosage
Standard Dosage
Adults:
- The standard dosage of Trelegy Ellipta is one inhalation (fluticasone propionate 100 mcg/formoterol fumarate dihydrate 6 mcg/glycopyrronium bromide 25 mcg) twice daily, administered as two inhalations in the morning and two inhalations in the evening. Dosages of other brands/generics may vary; refer to each brand’s information.
Children:
- This combination is not recommended for children below 18 years of age.
Special Cases:
- Elderly Patients: No dosage adjustment is typically required in elderly patients.
- Patients with Renal Impairment: No dosage adjustment is typically necessary.
- Patients with Hepatic Dysfunction: Caution is recommended, but specific dosage adjustments may not be required.
- Patients with Comorbid Conditions: Patients with cardiovascular disease, diabetes, glaucoma, cataracts, osteoporosis, or thyroid disorders should be monitored closely, and dosage adjustments may be necessary. Patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction should also be monitored.
Clinical Use Cases
- This medication is intended for long-term maintenance therapy of COPD. It is not indicated for use in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Dosage adjustments may be necessary based on individual patient response and tolerability.
Side Effects
Common Side Effects
- Headache, sore throat, stuffy nose, throat irritation, cough, chest tightness, dry mouth, constipation, upper respiratory tract infection, oral candidiasis (thrush).
Rare but Serious Side Effects
- Paradoxical bronchospasm, allergic reactions (including rash, hives, angioedema), cardiovascular events (e.g., palpitations, tachycardia), pneumonia, decreased bone mineral density, eye problems (glaucoma, cataracts), adrenal insufficiency, urinary retention, hypokalemia, hyperglycemia, seizures.
Long-Term Effects
- Prolonged use may lead to osteoporosis, adrenal suppression, growth retardation in children (although not indicated for children below 18), glaucoma, cataracts, increased risk of infections.
Adverse Drug Reactions (ADR)
- Angioedema, severe bronchospasm, anaphylaxis, severe cardiovascular events (e.g., arrhythmias), symptomatic hypokalemia.
Contraindications
- Hypersensitivity to fluticasone, formoterol, glycopyrrolate, or any component of the formulation.
- Primary treatment of status asthmaticus or other acute exacerbations of COPD.
- Severe allergy to milk proteins (some formulations contain lactose).
Drug Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): May increase fluticasone exposure.
- Beta-blockers (e.g., propranolol, metoprolol): May antagonize the bronchodilating effects of formoterol.
- Diuretics (e.g., furosemide, hydrochlorothiazide): May cause additive hypokalemia.
- MAOIs and TCAs (e.g., phenelzine, amitriptyline): May potentiate cardiovascular effects.
- Bronchodilators (salbutamol, aminophylline, theophylline), other steroids (budesonide, prednisone, mometasone, beclometasone), some heart medications (sotalol, digoxin, disopyramide, procainamide, quinidine), some antibiotics (telithromycin, furazolidone, clarithromycin).
- Other COPD medications (e.g., tiotropium, umeclidinium, vilanterol).
Pregnancy and Breastfeeding
- Safety during pregnancy and breastfeeding has not been established. Use only if the potential benefit outweighs the potential risk to the fetus or infant.
Drug Profile Summary
- Mechanism of Action: Anti-inflammatory (fluticasone), bronchodilating (formoterol and glycopyrrolate).
- Side Effects: Headache, sore throat, cough, dry mouth, thrush, paradoxical bronchospasm, allergic reactions, hypokalemia, hyperglycemia.
- Contraindications: Hypersensitivity, acute asthma/COPD exacerbations, milk protein allergy.
- Drug Interactions: CYP3A4 inhibitors, beta-blockers, diuretics, MAOIs, TCAs.
- Pregnancy & Breastfeeding: Not established; use with caution.
- Dosage: One inhalation twice daily.
- Monitoring Parameters: Lung function (FEV1), blood glucose, potassium levels, symptoms of COPD, adverse effects.
Popular Combinations
- While this triple combination itself is a popular combination, the individual components are often used in other combination products. Examples include:
- Fluticasone/salmeterol
- Budesonide/formoterol
- Umeclidinium/vilanterol
Precautions
- Evaluate for hypersensitivity, glaucoma, cardiovascular disease, diabetes, osteoporosis, thyroid disorders, hepatic or renal impairment prior to initiating treatment.
FAQs (Frequently Asked Questions)
A: The typical dosage for Trelegy Ellipta is one inhalation twice daily. Other brands may have varying dosages - refer to each product’s information.
Q2: Can this medication be used for acute COPD exacerbations?
A: No, this medication is not indicated for the relief of acute bronchospasm. A short-acting bronchodilator (e.g., albuterol) should be used for acute symptom relief.
Q3: What are the most common side effects?
A: Common side effects include headache, sore throat, cough, dry mouth, and thrush.
Q4: Are there any serious drug interactions to be aware of?
A: Yes, significant interactions can occur with strong CYP3A4 inhibitors, beta-blockers, diuretics, MAOIs, and TCAs.
Q5: Can this medication be used in patients with asthma?
A: No, this medication is not indicated for the treatment of asthma. Other ICS/LABA combinations are available for asthma management.
Q6: What should I monitor in patients taking this medication?
A: Monitor lung function (FEV1), blood glucose levels, potassium levels, symptoms of COPD, and any adverse effects.
Q7: What are the contraindications to using this medication?
A: Contraindications include hypersensitivity to any of the components, primary treatment of acute asthma/COPD exacerbations, and severe milk protein allergy.
Q8: Can this combination be used in pregnant or breastfeeding women?
A: Safety in pregnancy and lactation is not established. Use only if the potential benefit clearly outweighs the potential risk to the fetus or nursing infant.
Q9: What is the mechanism of action of each component of this medication?
A: Fluticasone: Reduces airway inflammation; Formoterol: Relaxes and widens airways; Glycopyrrolate: Enhances bronchodilation and reduces mucus secretions.
Q10: How is this medication administered?
A: It is administered via oral inhalation using a specific inhaler device.
