Introduction
Breyna is a combination inhalation aerosol containing budesonide (an inhaled corticosteroid) and formoterol (a long-acting beta2-adrenergic agonist). It is approved for the maintenance treatment of asthma and prevention of bronchospasm in patients with chronic obstructive pulmonary disease (COPD). This fixed-dose combination provides both anti-inflammatory and bronchodilator effects in a single delivery device.
Mechanism of Action
Budesonide: A synthetic corticosteroid that exerts potent anti-inflammatory effects by inhibiting multiple inflammatory cells and decreasing the production of inflammatory mediators. It reduces airway hyperresponsiveness, mucus production, and mucosal edema. Formoterol: A long-acting beta2-adrenergic agonist that stimulates intracellular adenyl cyclase, increasing cyclic adenosine monophosphate (cAMP) production. This results in relaxation of bronchial smooth muscle and inhibition of immediate hypersensitivity mediator release from mast cells.The combination provides complementary mechanisms addressing both inflammation and bronchoconstriction in obstructive airway diseases.
Indications
- Asthma: Maintenance treatment of asthma in patients 12 years and older
- COPD: Maintenance treatment of airflow obstruction and reducing exacerbations in patients with COPD
- Exercise-induced bronchoconstriction: Prevention in patients 12 years and older (not for acute relief)
Dosage and Administration
Asthma:- Adults and adolescents (12+ years): 2 inhalations twice daily (morning and evening)
- Maximum dose: 4 inhalations twice daily
- Adults: 2 inhalations twice daily
- Shake well before each inhalation
- Prime before first use or if not used for more than 7 days
- Rinse mouth after inhalation to reduce risk of oropharyngeal candidiasis
- Not for acute bronchospasm relief
- Hepatic impairment: Use with caution
- Renal impairment: No dosage adjustment required
- Elderly: No dosage adjustment required
- Pediatrics: Not recommended for children under 12 years
Pharmacokinetics
Absorption:- Budesonide: Systemic bioavailability approximately 39% of delivered dose
- Formoterol: Rapid absorption with peak plasma concentrations within 10-30 minutes
- Budesonide: Volume of distribution ~3 L/kg, 88-90% protein bound
- Formoterol: Volume of distribution ~4 L/kg, 50-65% protein bound
- Budesonide: Extensive first-pass metabolism via CYP3A4
- Formoterol: Hepatic metabolism via glucuronidation and O-demethylation
- Budesonide: Terminal half-life 2-3 hours, excreted primarily in urine and feces
- Formoterol: Terminal half-life 10-14 hours, excreted primarily in urine
Contraindications
- Hypersensitivity to budesonide, formoterol, or any component
- Primary treatment of status asthmaticus or other acute episodes of asthma or COPD
- Significant hypersensitivity to milk proteins
Warnings and Precautions
Boxed Warning: Long-acting beta2-adrenergic agonists may increase the risk of asthma-related death. Breyna should only be used for patients not adequately controlled on other asthma-controller medications. Additional Warnings:- Paradoxical bronchospasm: Discontinue immediately if occurs
- Cardiovascular effects: May cause significant cardiovascular effects including increases in pulse rate and blood pressure
- Systemic corticosteroid effects: May occur, particularly at higher doses
- Immunosuppression: Increased risk of infections
- Reduced bone mineral density: With long-term use
- Glaucoma and cataracts: Regular ophthalmological exams recommended
- Hypokalemia and hyperglycemia: May occur, monitor particularly in diabetic patients
Drug Interactions
Strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin): May increase budesonide concentrations - use with caution Beta-blockers: May antagonize bronchodilator effects - use with caution Diuretics: May potentiate hypokalemic effects MAO inhibitors and tricyclic antidepressants: May potentiate cardiovascular effects QT-prolonging drugs: Additive effects possibleAdverse Effects
Most common (>5%):- Headache
- Pharyngitis
- Upper respiratory tract infection
- Oral candidiasis
- Hoarseness
- Cough
- Tremor
- Palpitations
- Paradoxical bronchospasm
- Cardiovascular events (tachycardia, hypertension, arrhythmias)
- Pneumonia (in COPD patients)
- Adrenal suppression
- Severe hypersensitivity reactions
- Worsening of diabetes mellitus
Monitoring Parameters
Clinical monitoring:- Pulmonary function tests (FEV1, peak flow)
- Asthma/COPD symptom control
- Exacerbation frequency
- Growth velocity in pediatric patients
- Serum potassium (particularly during exacerbations)
- Blood glucose in diabetic patients
- Bone mineral density with long-term use
- Ophthalmological exams (cataracts, glaucoma)
- Signs/symptoms of infection
- Adrenal function during stress or tapering
Patient Education
Proper use:- Demonstrate correct inhalation technique
- Not for acute symptom relief - keep rescue inhaler available
- Use regularly even when asymptomatic
- Do not exceed prescribed dosage
- Rinse mouth after each use to prevent oral thrush
- Clean inhaler regularly as directed
- Prime device if not used for several days
- Keep track of number of doses used
- Worsening breathing problems
- Need for more rescue inhaler use
- Chest pain, rapid heartbeat, or tremors
- Signs of infection (fever, chills)
- Vision changes
- Store at room temperature
- Keep away from extreme heat or cold
- Do not puncture or incinerate
References
1. FDA Prescribing Information: Breyna (budesonide/formoterol fumarate) Inhalation Aerosol 2. Global Initiative for Asthma (GINA) Guidelines, 2023 3. Global Initiative for Chronic Obstructive Lung Disease (GOLD) Report, 2023 4. Nelson HS, et al. The efficacy and safety of budesonide/formoterol pressurized metered-dose inhaler in patients with asthma. Allergy Asthma Proc. 2019 5. Tashkin DP, et al. Efficacy and safety of budesonide/formoterol in one pressurized metered-dose inhaler in patients with chronic obstructive pulmonary disease. COPD. 2016 6. American Thoracic Society/European Respiratory Society guidelines on asthma management 7. Drug Interaction Facts: Facts & Comparisons