Usage
- Medical Conditions: Formoterol + Glycopyrrolate 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 for the treatment of asthma.
- Pharmacological Classification: This drug is a combination of two bronchodilators:
- Formoterol: Long-acting beta2-adrenergic agonist (LABA)
- Glycopyrrolate: Long-acting muscarinic antagonist (LAMA)
- Mechanism of Action: Formoterol relaxes the smooth muscle in the airways, leading to bronchodilation. Glycopyrrolate blocks the bronchoconstricting effect of acetylcholine on airway smooth muscle, further enhancing bronchodilation.
Alternate Names
- International/Regional Variations: Glycopyrronium/formoterol fumarate
- Brand Names: Bevespi Aerosphere
How It Works
- Pharmacodynamics: Formoterol, a LABA, stimulates beta2-adrenergic receptors in the lungs, activating adenylate cyclase and increasing intracellular cyclic adenosine monophosphate (cAMP). This leads to smooth muscle relaxation and bronchodilation. Glycopyrrolate, a LAMA, competitively inhibits the action of acetylcholine at muscarinic M3 receptors on airway smooth muscle, preventing bronchoconstriction.
- Pharmacokinetics: Both drugs are administered via inhalation. Formoterol is rapidly absorbed, metabolized primarily in the liver by CYP2D6 and CYP2C19, and excreted mainly in the urine. Glycopyrrolate exhibits slower absorption, limited systemic availability due to low oral bioavailability, and is excreted primarily unchanged in the urine.
- Mode of Action: Formoterol acts by stimulating beta2-adrenergic receptors, while Glycopyrrolate acts by blocking muscarinic M3 receptors.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Formoterol binds to beta2-adrenergic receptors, while Glycopyrrolate binds to and blocks muscarinic M3 receptors. Formoterol is metabolized by CYP2D6 and CYP2C19 enzymes.
- Elimination Pathways: Formoterol is eliminated through hepatic metabolism (CYP2D6, CYP2C19) and renal excretion. Glycopyrrolate is eliminated primarily through renal excretion.
Dosage
Standard Dosage
Children: Use is not recommended.
Special Cases:
- Elderly Patients: No specific dose adjustment is required based solely on age. Monitor for potential adverse effects.
- Patients with Renal Impairment: Use with caution in severe renal impairment (CrCl ≤30 mL/min/1.73 m²) or end-stage renal disease.
- Patients with Hepatic Dysfunction: Use with caution as formoterol is metabolized in the liver. Monitor closely for adverse events.
- Patients with Comorbid Conditions: Assess patient-specific factors and adjust the dose as needed.
Clinical Use Cases
This medication is intended for maintenance treatment of COPD. It is not indicated for:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
- Dose modifications may be required based on patient’s renal/hepatic function, other medical conditions, and concomitant medications.
Side Effects
Common Side Effects:
- Dry mouth
- Upper respiratory tract infection
- Headache
- Back pain
Rare but Serious Side Effects:
- Paradoxical bronchospasm
- Worsening of COPD
- Cardiovascular effects (e.g., increased heart rate, palpitations)
- Urinary retention
Long-Term Effects:
- Potential for reduced lung function decline. Closely monitor patients for changes in respiratory status.
- Osteoporosis with long-term inhaled corticosteroid use (if part of a combination product with a corticosteroid like budesonide). Formoterol/glycopyrrolate combination products do not contain corticosteroids.
Adverse Drug Reactions (ADR):
- Angioedema
- Hypersensitivity reactions
Contraindications
- Hypersensitivity to formoterol, glycopyrrolate, or any of the excipients.
Drug Interactions
- Beta-blockers: May antagonize the bronchodilatory effects of formoterol.
- Other anticholinergic drugs: May increase the risk of anticholinergic adverse effects.
- Diuretics: May enhance hypokalemia associated with beta-agonists.
- Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants: May potentiate the cardiovascular effects of formoterol.
- QT prolonging drugs: May increase the risk of QT interval prolongation with formoterol.
Pregnancy and Breastfeeding
- Pregnancy: No adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: It is unknown whether glycopyrrolate or formoterol are excreted in human milk. Exercise caution when administering to nursing women.
Drug Profile Summary
- Mechanism of Action: Bronchodilation via LABA and LAMA mechanisms.
- Side Effects: Dry mouth, upper respiratory infection, headache, back pain, paradoxical bronchospasm, cardiovascular effects.
- Contraindications: Hypersensitivity.
- Drug Interactions: Beta-blockers, other anticholinergics, diuretics, MAOIs, tricyclic antidepressants, QT prolonging drugs.
- Pregnancy & Breastfeeding: Use with caution if potential benefit outweighs risk.
- Dosage: Two inhalations twice daily.
- Monitoring Parameters: Pulmonary function tests (e.g., FEV1), heart rate, blood pressure, symptoms of COPD exacerbation.
Popular Combinations
Formoterol and glycopyrrolate are sometimes combined with inhaled corticosteroids (ICS) such as budesonide (e.g., Breztri Aerosphere) for patients whose COPD is not adequately controlled with two bronchodilators.
Precautions
- Assess for underlying cardiovascular disease and other medical conditions.
- Patients with narrow-angle glaucoma, prostatic hyperplasia, or bladder-neck obstruction should use with caution.
- Monitor for paradoxical bronchospasm.
FAQs (Frequently Asked Questions)
A: Two inhalations (9 mcg glycopyrrolate/4.8 mcg formoterol per inhalation) twice daily (morning and evening).
Q2: Can this medication be used for asthma?
A: No, formoterol + glycopyrrolate is not indicated for the treatment of asthma.
Q3: What are the most common side effects?
A: Dry mouth, upper respiratory tract infection, headache, and back pain.
Q4: Are there any serious side effects I should be aware of?
A: Yes, rare but serious side effects can include paradoxical bronchospasm, worsening of COPD, cardiovascular effects, and urinary retention.
Q5: What are the contraindications for this medication?
A: Known hypersensitivity to formoterol, glycopyrrolate, or any components of the formulation.
Q6: Can this drug be used in patients with renal impairment?
A: Use with caution in patients with severe renal impairment. Closely monitor these patients.
Q7: How should this drug be administered?
A: Via oral inhalation using the metered-dose inhaler. Rinse your mouth after use without swallowing.
Q8: What should I do if a patient experiences paradoxical bronchospasm?
A: Discontinue the medication immediately and provide alternative bronchodilator therapy.
Q9: Is there a specific dosage adjustment for elderly patients?
A: No specific dosage adjustment is recommended based solely on age, but elderly patients should be monitored closely for potential adverse effects.
A: Yes, clinically significant interactions can occur with beta-blockers, other anticholinergics, diuretics, MAOIs, tricyclic antidepressants, and drugs that prolong the QT interval.
