What are alternative inhaled corticosteroid/long‑acting β2‑agonist (ICS/LABA) combinations to Symbicort (budesonide + formoterol)?

Alternative ICS/LABA Combinations to Symbicort

The primary alternatives to Symbicort (budesonide/formoterol) are fluticasone/salmeterol (Advair), mometasone/formoterol (Dulera), and fluticasone/vilanterol (Breo Ellipta), with the choice depending on whether you need rapid-onset bronchodilation for rescue therapy. 1

Key Decision Point: Maintenance-Only vs. SMART Regimen

If your patient requires a SMART regimen (Single Maintenance And Reliever Therapy):

• Only formoterol-containing products can be used because formoterol has rapid onset of action (within 1 minute), while salmeterol has delayed onset 1, 2
• Mometasone/formoterol is the primary alternative that theoretically could work for SMART, though studies were performed almost exclusively with budesonide/formoterol 1
• Never use salmeterol-based combinations (fluticasone/salmeterol) for SMART regimen 1

If your patient only needs fixed-dose maintenance therapy (not SMART):

• Fluticasone/salmeterol (Advair) is well-established with extensive evidence in both asthma and COPD 1, 3
• Fluticasone/vilanterol (Breo Ellipta) offers once-daily dosing convenience 1
• Mometasone/formoterol (Dulera) provides twice-daily dosing 1
• Beclomethasone/formoterol (Foster) is available in some countries 3

Evidence Comparing Alternatives

For asthma patients aged ≥16 years:

• Budesonide/formoterol reduced hospitalizations/emergency room visits by 28% compared to fixed-dose fluticasone/salmeterol (relative rate 0.72, p=0.034) 3
• All ICS/LABA combinations provide similar improvements in lung function, asthma control days, and quality of life 3

For COPD patients:

• Current evidence suggests budesonide/formoterol may have similar or superior effects on reducing exacerbations compared to other ICS/LABA combinations 4
• Budesonide/formoterol may be associated with lower incidence of serious pneumonia events compared to other ICS/LABA combinations 4
• All ICS/LABA combinations increase pneumonia risk by approximately 4% compared to LABA monotherapy alone 1

Critical Caveats

SMART regimen considerations:

• SMART is currently off-label use in the United States despite removal of the boxed warning regarding asthma-related death 1
• SMART should not be used in children under 12 years old per NAEPP guidelines 1, 2
• Maximum total daily formoterol dose should not exceed 24 mcg (approximately 5 inhalations of 160/4.5 mcg strength) 2

Insurance and practical issues:

• If insurance covers only one canister but patient needs SMART, you could theoretically prescribe one ICS/LABA for maintenance and another formoterol-containing product as reliever, though this strategy has never been formally tested 1
• Ensure patient clearly understands which inhaler to use as reliever if using different products 1

Algorithm for Selection

1. Determine if SMART regimen is needed (moderate-to-severe asthma, steps 3-4 in patients ≥12 years) 1, 2

   • Yes → Use formoterol-containing product only: mometasone/formoterol or continue budesonide/formoterol
   • No → Any ICS/LABA acceptable: fluticasone/salmeterol, fluticasone/vilanterol, mometasone/formoterol

2. Consider dosing frequency preference:

   • Once-daily: fluticasone/vilanterol 1
   • Twice-daily: fluticasone/salmeterol, mometasone/formoterol, beclomethasone/formoterol 1, 3

3. For COPD patients with high exacerbation risk:

   • Consider LABA/LAMA over ICS/LABA as primary choice due to pneumonia risk 5
   • If ICS/LABA needed, budesonide/formoterol may have lower pneumonia risk than other combinations 4