What is a good alternative to Advair (fluticasone and salmeterol) HFA 45?

Alternative to Advair HFA 45 (Fluticasone/Salmeterol 45/21 mcg)

The best alternative to Advair HFA 45/21 mcg is budesonide/formoterol (Symbicort) 80/4.5 mcg, which provides equivalent or superior asthma control with the added advantage of being usable as both maintenance and rescue therapy. 1, 2

Primary Alternative: Budesonide/Formoterol (Symbicort)

Budesonide/formoterol is the preferred alternative because it offers several clinical advantages over fluticasone/salmeterol combinations:

• Formoterol's rapid onset of action (similar to albuterol) allows it to function as both a controller and reliever medication, unlike salmeterol which has a slower onset 1, 3
• In head-to-head trials with adults, budesonide/formoterol reduced hospitalizations/emergency room visits by 28% compared to salmeterol/fluticasone propionate (RR 0.72; 95% CI 0.53,0.98; p = 0.034) 2
• The SMART protocol (Single Maintenance and Reliever Therapy) using budesonide/formoterol is extensively validated and endorsed by the American College of Allergy, Asthma, and Immunology 1

Dosing Recommendation

• For mild-to-moderate persistent asthma: Start with budesonide/formoterol 80/4.5 mcg, 2 inhalations twice daily for maintenance, plus additional inhalations as needed for symptom relief (maximum 8 puffs/day for ages 5-11, or 10 puffs/day for ages ≥12) 1

Secondary Alternative: Fluticasone Furoate/Vilanterol (Breo Ellipta)

If once-daily dosing is preferred or adherence is a concern:

• Breo Ellipta 100/25 mcg once daily provides comparable efficacy to twice-daily ICS/LABA combinations 4, 5
• This is a newer-generation ICS/LABA with 24-hour duration of action 4
• Important caveat: Vilanterol, like salmeterol, has a slower onset and cannot be used for acute symptom relief—patients must have a separate short-acting beta-agonist (SABA) for rescue 4

Step-Therapy Alternatives Based on Asthma Severity

The American Academy of Family Physicians provides a stepwise approach 1:

For Mild Persistent Asthma (Step 2):

• Low-dose ICS monotherapy (fluticasone/Flovent, budesonide/Pulmicort, or beclomethasone/QVAR) may be sufficient 1
• Alternative: Leukotriene modifiers (montelukast/Singulair) if ICS is not tolerated, though less effective than ICS 6, 1

For Moderate Persistent Asthma (Step 3):

• Preferred: Low-dose ICS/LABA combinations (budesonide/formoterol or fluticasone/salmeterol) 1
• Alternative: Medium-dose ICS monotherapy or low-dose ICS plus leukotriene modifier 1

Critical Safety Considerations

Never use LABA monotherapy without an inhaled corticosteroid—this is associated with increased risk of asthma-related death and hospitalization 4, 5

• The Salmeterol Multicenter Asthma Research Trial (SMART) demonstrated a 4.37-fold increased risk of asthma-related death with LABA monotherapy (95% CI: 1.25,15.34) 5
• All LABA-containing products must be combined with ICS to mitigate this risk 4, 5

Common Pitfalls to Avoid

• Do not prescribe salmeterol-containing products (like Advair) for SMART protocol—salmeterol's slower onset makes it unsuitable as a rescue medication 1
• Ensure patients rinse mouth after ICS/LABA use to reduce risk of oropharyngeal candidiasis 4, 5
• Monitor for pneumonia risk in COPD patients using ICS-containing regimens, though this is less relevant for asthma patients 6
• Avoid frequent SABA use before exercise as this may mask poorly controlled persistent asthma requiring step-up therapy 1

Equivalency Considerations

When switching from Advair HFA 45/21 mcg (low dose):

• Budesonide/formoterol 80/4.5 mcg provides comparable ICS potency 2
• Fluticasone furoate/vilanterol 100/25 mcg provides slightly higher ICS exposure but once-daily convenience 4, 5
• There is no evidence of clinically significant differences between fluticasone/salmeterol and budesonide/formoterol combinations in subgroup analyses (χ² = 1.57, p = 0.21) 6