Usage
Budesonide + Formoterol + Glycopyrrolate is prescribed for the maintenance treatment of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema, in adults. It is not indicated for the relief of acute bronchospasm or for the treatment of asthma. This combination belongs to the pharmacological class of inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting beta2-adrenergic agonists (LABA). It works by reducing inflammation (budesonide), relaxing airway smooth muscle (formoterol), and blocking bronchoconstricting signals (glycopyrrolate), thereby improving airflow and reducing COPD exacerbations.
Alternate Names
This triple therapy is often referred to by its brand name, Breztri Aerosphere. There is currently no generic version available in most regions. In some regions, the brand name Trixeo Aerosphere or Riltrava Aerosphere are used.
How It Works
Pharmacodynamics: Budesonide exerts its anti-inflammatory effects by binding to glucocorticoid receptors in the airways, reducing inflammatory cell activity and cytokine production. Formoterol, a LABA, relaxes bronchial smooth muscle by stimulating beta2-adrenergic receptors. Glycopyrrolate, a LAMA, blocks the action of acetylcholine at muscarinic receptors, thereby inhibiting bronchoconstriction.
Pharmacokinetics: All three components are administered via inhalation. Budesonide is systemically absorbed, extensively metabolized by CYP3A4 enzymes in the liver, and primarily excreted in the urine and feces. Formoterol undergoes some metabolism and is primarily eliminated via renal excretion. Glycopyrrolate exhibits low systemic absorption with predominantly renal excretion.
Dosage
Standard Dosage
Adults:
The standard dosage is two inhalations twice daily (morning and evening). Each inhalation of Breztri Aerosphere delivers 160 mcg of budesonide, 4.8 mcg of formoterol fumarate, and 9 mcg of glycopyrrolate. Do not exceed the maximum dose of two inhalations twice daily. Rinse your mouth with water after each use without swallowing.
Children:
This medication is not recommended for use in children under 18 years of age as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: No dosage adjustment is generally required.
- Patients with Renal Impairment: Caution is advised in patients with severe renal impairment or end-stage renal disease. While no specific dose adjustment is recommended, use should be considered only if the benefit outweighs the risk. Close monitoring is advised.
- Patients with Hepatic Dysfunction: Close monitoring is recommended for patients with severe hepatic impairment as both budesonide and formoterol are primarily metabolized by the liver, and increased systemic exposure may occur.
- Patients with Comorbid Conditions: Caution should be exercised in patients with diabetes, cardiovascular disease, narrow-angle glaucoma, urinary retention, osteoporosis, hyperthyroidism, hypokalemia, and those prone to seizures. Close monitoring is advisable, especially for blood glucose levels in patients with diabetes.
Clinical Use Cases
This medication is not indicated for:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Its usage is specifically for the maintenance treatment of COPD and should not be used as a rescue medication for acute exacerbations.
Dosage Adjustments
Dosage adjustments may be necessary based on individual patient factors such as renal or hepatic impairment and response to therapy. Closely monitor patients for adverse effects and therapeutic response.
Side Effects
Common Side Effects
- Upper respiratory tract infections (including common cold, nasopharyngitis, influenza)
- Oral candidiasis (thrush)
- Headache
- Back pain
- Muscle spasms
- Cough
- Hoarseness
- Nausea, vomiting, diarrhea
- Urinary tract infection
Rare but Serious Side Effects
- Pneumonia
- Hypersensitivity reactions (including angioedema, urticaria, rash, and bronchospasm)
- Hyperglycemia
- Hypokalemia
- Cardiovascular effects (e.g., palpitations, tachycardia, arrhythmias)
- Worsening of glaucoma
- Adrenal suppression (with prolonged use)
Long-Term Effects
- Osteoporosis (with prolonged use)
- Cataracts
- Increased risk of infections
Adverse Drug Reactions (ADR)
Severe allergic reactions, paradoxical bronchospasm, significant cardiovascular effects (arrhythmias, QT prolongation), and severe hypokalemia require immediate medical attention.
Contraindications
- Hypersensitivity to budesonide, formoterol, glycopyrrolate, or any of the excipients.
- Primary treatment of acute bronchospasm or status asthmaticus.
- Asthma (not indicated for the treatment of Asthma).
Drug Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir): may increase budesonide exposure and risk of systemic side effects.
- Beta-blockers: may antagonize the bronchodilating effects of formoterol.
- Other long-acting beta2-agonists: may increase the risk of adverse effects.
- Anticholinergics (e.g., tiotropium): may enhance anticholinergic effects.
- Diuretics: may potentiate hypokalemia caused by formoterol.
- Tricyclic antidepressants (TCAs), Monoamine oxidase inhibitors (MAOIs): may potentiate cardiovascular effects.
- Medications that prolong the QT interval: additive risk of arrhythmias.
Pregnancy and Breastfeeding
- Pregnancy: Limited data available. Use only if the potential benefit to the mother outweighs the potential risk to the fetus. Inhaled budesonide has not been associated with an increased risk of teratogenicity.
- Breastfeeding: Budesonide is excreted in breast milk, but its effects on nursing infants are unknown. It is unknown whether glycopyrrolate or formoterol are excreted in human milk. Exercise caution and weigh the risks and benefits.
Drug Profile Summary
- Mechanism of Action: Anti-inflammatory (budesonide), bronchodilating (formoterol), and anticholinergic (glycopyrrolate) effects.
- Side Effects: Common: oral candidiasis, upper respiratory tract infections, headache, back pain. Serious: pneumonia, hypersensitivity reactions, hyperglycemia, hypokalemia, cardiovascular effects.
- Contraindications: Hypersensitivity, primary treatment of acute bronchospasm or status asthmaticus, Asthma.
- Drug Interactions: CYP3A4 inhibitors, beta-blockers, other LABAs, anticholinergics, diuretics, TCAs, MAOIs.
- Pregnancy & Breastfeeding: Limited data; use with caution.
- Dosage: 2 inhalations twice daily.
- Monitoring Parameters: Pulmonary function tests (FEV1), blood glucose levels (especially in diabetic patients), serum potassium, signs and symptoms of COPD exacerbation, ophthalmological assessments (in patients with glaucoma).
Popular Combinations
Budesonide + Formoterol + Glycopyrrolate is itself a combination product. It is generally not combined with other inhaled corticosteroids, LABAs, or LAMAs. However, short-acting beta2-agonists (SABAs) like albuterol can be used as rescue medication for acute exacerbations.
Precautions
- General Precautions: Assess for hypersensitivity, underlying medical conditions (especially cardiovascular, renal, hepatic, or ophthalmological conditions), and concomitant medications before initiating therapy. Monitor for adverse effects and therapeutic response.
- Specific Populations: See above under “Dosage - Special Cases”.
- Lifestyle Considerations: Smoking cessation is crucial for managing COPD. Patients should be advised on proper inhaler technique.
FAQs (Frequently Asked Questions)
A: The recommended dosage is two inhalations twice daily, administered morning and evening.
Q2: Can this medication be used to treat asthma?
A: No, this medication is not indicated for the treatment of asthma.
Q3: Can this medication be used as a rescue inhaler?
A: No, this medication is for maintenance treatment of COPD and not for acute symptom relief. Patients should use a short-acting beta2-agonist (SABA) like albuterol as a rescue inhaler.
Q4: What are the common side effects?
A: Common side effects include oral candidiasis (thrush), upper respiratory tract infections, headache, back pain, and muscle spasms.
Q5: What are the serious side effects?
A: Serious side effects may include pneumonia, hypersensitivity reactions, hyperglycemia, hypokalemia, and cardiovascular effects.
Q6: What are the contraindications?
A: Contraindications include hypersensitivity to any of the components, primary treatment of acute bronchospasm, and Asthma.
Q7: What are the important drug interactions?
A: Important drug interactions include strong CYP3A4 inhibitors, beta-blockers, other LABAs, anticholinergics, diuretics, TCAs, and MAOIs.
Q8: Can this medication be used during pregnancy or breastfeeding?
A: Limited data are available regarding use during pregnancy and breastfeeding. Use with caution and only if the potential benefit outweighs the potential risk.
Q9: How should this medication be administered?
A: Administer two inhalations twice daily via oral inhalation, using proper inhaler technique. Rinse the mouth with water after each use without swallowing.
Q10: What monitoring parameters are important?
A: Monitor pulmonary function, blood glucose levels (in patients with diabetes), potassium levels, signs of COPD exacerbations, and (if applicable) ophthalmological assessments.
