What are the side effects of Breztri (budesonide, glycopyrrolate, and formoterol)?

Side Effects of Breztri (Budesonide/Glycopyrrolate/Formoterol)

Breztri causes both local oropharyngeal effects and systemic adverse reactions, with the most common being oral thrush, voice changes, throat irritation, and cough from the inhaled corticosteroid component, while serious concerns include pneumonia risk in COPD patients and potential adrenal suppression at higher doses. 1

Common Local Side Effects

The inhaled corticosteroid (budesonide) component produces predictable local effects:

• Oral thrush (candidiasis) is a frequent local side effect that can be minimized by rinsing the mouth after each inhalation 1
• Dysphonia (voice changes) and pharyngeal irritation occur commonly with the budesonide component 1
• Throat irritation is reported as a common local adverse reaction 1
• Cough can occur upon administration of the inhaled corticosteroid 1

Common Systemic Side Effects

The budesonide component can produce systemic effects, particularly with long-term use:

• Adrenal suppression can occur at higher doses of inhaled corticosteroids, especially when combined with CYP3A4 inhibitors like ritonavir or ketoconazole 1
• Growth suppression in children has been observed, though this effect may be transient 1
• Skin thinning and easy bruising can develop with long-term use at higher doses 1
• Bone effects, including potential risk of osteoporosis, occur with prolonged use at higher doses 1

Serious Adverse Reactions

Pneumonia risk is significantly elevated in COPD patients using inhaled corticosteroid-containing regimens like Breztri. 1 This represents one of the most clinically important adverse effects to monitor.

• Cushing syndrome and secondary adrenal insufficiency have been reported, particularly when Breztri is used concurrently with potent CYP3A4 inhibitors 1

Beta-Agonist and Anticholinergic Effects

From the formoterol (LABA) component:

• Tachycardia (rapid heart rate) can occur 2
• Skeletal muscle tremor is a known beta-agonist effect 2
• Hypokalemia (low potassium) may develop 2

Risk Factors That Increase Adverse Effects

• Drug interactions with CYP3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, clarithromycin) can dramatically increase systemic budesonide concentrations and risk of systemic corticosteroid effects 1

Strategies to Minimize Side Effects

Proper inhaler technique with mouth rinsing after each use is the single most effective strategy to reduce local side effects. 1

• Use a spacer or valved holding chamber with the MDI to minimize oropharyngeal deposition and local side effects 1
• Rinse mouth thoroughly after inhalation to decrease oral candidiasis and throat irritation 1
• Dose optimization using the lowest effective dose to maintain COPD control minimizes systemic adverse effects 1
• Regular monitoring for systemic effects is recommended in patients on long-term triple therapy, including periodic assessment for adrenal function, bone density, and growth in children 1

Special Population Considerations

• COPD patients have an increased risk of pneumonia compared to patients using long-acting beta-agonists alone, requiring vigilance for respiratory infections 1
• Pediatric patients require special monitoring for growth suppression, though budesonide is the only inhaled corticosteroid with FDA approval for children under 4 years of age 1

Critical Safety Caveat

The mortality benefit observed with Breztri in the ETHOS trial (51% reduction in all-cause mortality compared to glycopyrrolate/formoterol) 3 must be weighed against the pneumonia risk, particularly in patients with severe COPD and frequent exacerbations. Close monitoring for respiratory infections is essential during treatment.