Usage
Glycopyrronium + Vilanterol is prescribed for the long-term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. It is not indicated for the relief of acute bronchospasm or the treatment of asthma.
This fixed-dose combination medication belongs to the bronchodilator class and comprises a long-acting muscarinic antagonist (LAMA), Glycopyrronium, and a long-acting beta2-adrenergic agonist (LABA), Vilanterol.
Glycopyrronium blocks the action of acetylcholine at M3 muscarinic receptors in the lungs, leading to bronchodilation. Vilanterol stimulates beta2-adrenergic receptors, resulting in relaxation of airway smooth muscle and bronchodilation. The combined action of these two components provides synergistic bronchodilation.
Alternate Names
While “Glycopyrronium + Vilanterol” represents the generic name, this combination is marketed under the brand name Bevespi Aerosphere. Formoterol is an alternate name for Vilanterol.
How It Works
Pharmacodynamics: Glycopyrronium, as a LAMA, competitively inhibits the binding of acetylcholine to M3 muscarinic receptors in bronchial smooth muscle, reducing bronchoconstriction. Vilanterol, as a LABA, stimulates beta2-adrenergic receptors, activating adenylate cyclase and increasing intracellular cyclic AMP levels. This leads to relaxation of bronchial smooth muscle and bronchodilation. The combination produces synergistic bronchodilation.
Pharmacokinetics:
- Glycopyrronium: Following inhalation, approximately 40% of the dose is systemically absorbed. Peak plasma concentrations are achieved rapidly (around 5 minutes). It is predominantly eliminated renally, primarily in its unchanged form.
- Vilanterol: After inhalation, it exhibits high plasma clearance. It is extensively metabolized by CYP3A4 enzymes in the liver.
Mode of Action: The two components act on distinct pathways to achieve bronchodilation. Glycopyrronium acts through receptor antagonism, while Vilanterol acts through receptor agonism.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Glycopyrronium binds to and blocks M3 muscarinic receptors. Vilanterol binds to and activates beta2-adrenergic receptors. Vilanterol is metabolized by CYP3A4 enzymes.
Elimination Pathways: Glycopyrronium is primarily eliminated by renal excretion. Vilanterol is primarily eliminated by hepatic metabolism through CYP3A4 enzymes.
Dosage
Standard Dosage
Adults:
The standard dose of Glycopyrronium + Vilanterol (Bevespi Aerosphere) is two inhalations (puffs) in the morning and two inhalations in the evening, administered via the Aerosphere inhaler. Each puff contains 9 mcg of glycopyrronium and 4.8 mcg of formoterol.
Children:
Use is not recommended in pediatric patients.
Special Cases:
- Elderly Patients: No dose adjustment is necessary.
- Patients with Renal Impairment: No dose adjustment is necessary for mild to moderate impairment. For severe renal impairment (creatinine clearance ≤ 30 mL/min) or end-stage renal disease requiring dialysis, use only if the expected benefit outweighs the potential risk. Close monitoring is recommended.
- Patients with Hepatic Dysfunction: Since formoterol is primarily cleared by hepatic metabolism, impairment may lead to accumulation. Close monitoring is recommended.
- Patients with Comorbid Conditions: Careful consideration should be given to patients with cardiovascular disease, diabetes, narrow-angle glaucoma, urinary retention, or prostatic hyperplasia.
Clinical Use Cases
Glycopyrronium + Vilanterol is not indicated for acute situations such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is specifically for the maintenance treatment of COPD. A short-acting bronchodilator should be used for acute exacerbations.
Dosage Adjustments
Dose adjustments may be needed based on individual patient response and tolerability. Close monitoring of patients with renal or hepatic impairment is essential.
Side Effects
Common Side Effects:
- Headache
- Nasopharyngitis (common cold)
- Upper respiratory tract infection
- Back Pain
- Pneumonia
- Urinary tract infection
Rare but Serious Side Effects:
- Paradoxical bronchospasm
- Worsening of asthma symptoms (if misused for asthma)
- Cardiovascular effects (e.g., palpitations, tachycardia, QT prolongation)
- Angioedema, hypersensitivity
- Hyperglycemia
- Hypokalemia
- Urinary retention
- Narrow-angle glaucoma
Long-Term Effects:
Long-term effects are primarily related to the potential for cardiovascular complications, worsening of pre-existing conditions like glaucoma and urinary retention, and potential impact on bone mineral density with inhaled corticosteroids.
Adverse Drug Reactions (ADR):
Clinically significant ADRs primarily involve paradoxical bronchospasm, severe cardiovascular effects, and hypersensitivity reactions.
Contraindications
- Hypersensitivity to glycopyrronium, vilanterol, or any component of the formulation.
- Asthma (without concomitant inhaled corticosteroid).
Drug Interactions
- Beta-blockers: May antagonize the bronchodilatory effects of vilanterol.
- QT Prolonging Drugs: May increase the risk of QT prolongation and arrhythmias with vilanterol. Examples include certain antiarrhythmics, antibiotics, and antidepressants.
- CYP3A4 Inhibitors/Inducers: May affect the metabolism of vilanterol, necessitating dose adjustments.
- Diuretics: May exacerbate hypokalemia.
- Other LABAs or LAMAs: Concomitant use is not recommended due to the increased risk of adverse effects.
Pregnancy and Breastfeeding
Glycopyrronium + Vilanterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is unknown whether glycopyrronium or vilanterol are excreted in human milk. The decision to breastfeed during therapy should consider the potential risk to the infant.
Drug Profile Summary
- Mechanism of Action: LAMA (Glycopyrronium) and LABA (Vilanterol) combination producing synergistic bronchodilation.
- Side Effects: Common: Headache, nasopharyngitis, upper respiratory tract infection. Serious: Paradoxical bronchospasm, cardiovascular effects.
- Contraindications: Hypersensitivity, asthma (without ICS).
- Drug Interactions: Beta-blockers, QT prolonging drugs, CYP3A4 inhibitors/inducers, diuretics, other LABAs/LAMAs.
- Pregnancy & Breastfeeding: Use with caution; consider risks and benefits.
- Dosage: 2 inhalations BID (adults). Not recommended for children.
- Monitoring Parameters: Pulmonary function, cardiovascular status, serum potassium levels, blood glucose (in diabetics).
Popular Combinations
Glycopyrronium/formoterol is typically used as a standalone therapy. Triple therapy including an inhaled corticosteroid may be considered for some patients with severe COPD and frequent exacerbations.
Precautions
- General Precautions: Monitor for paradoxical bronchospasm, cardiovascular effects, and hyperglycemia. Assess renal and hepatic function.
- Specific Populations:
- Pregnant Women: Assess risk/benefit.
- Breastfeeding Mothers: Assess risk/benefit.
- Children & Elderly: Not recommended for children. Monitor elderly for adverse effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Glycopyrronium + Vilanterol?
A: Two inhalations twice daily (morning and evening) for adults. Not recommended for children.
Q2: Can this medication be used for acute exacerbations of COPD?
A: No, it’s for maintenance treatment. Use a rescue inhaler for acute symptoms.
Q3: What are the most common side effects?
A: Headache, nasopharyngitis, upper respiratory tract infection.
Q4: What are the serious side effects I should watch out for?
A: Paradoxical bronchospasm, cardiovascular effects, hyperglycemia, hypokalemia.
Q5: Can I use this with other LABAs or LAMAs?
A: No, concomitant use is not recommended due to increased risk of side effects.
Q6: What should I do if a patient experiences paradoxical bronchospasm?
A: Stop the medication immediately and consider alternative therapies.
Q7: Are there any drug interactions I should be aware of?
A: Yes, beta-blockers, QT prolonging agents, CYP3A4 inhibitors/inducers, and diuretics.
Q8: Can it be used in patients with renal or hepatic impairment?
A: Use with caution and monitor closely. Dose adjustment may be needed in severe renal impairment.
Q9: Is it safe to use during pregnancy and breastfeeding?
A: Use with caution. Weigh the benefits against potential risks to the fetus or infant. Consult with a specialist if necessary.
