In an otherwise healthy adult with persistent asthma and no inhaled corticosteroid hypersensitivity, is once‑daily fluticasone propionate 200 µg as effective as twice‑daily 100 µg for asthma control?

Fluticasone Propionate: Once-Daily vs Twice-Daily Dosing

For fluticasone propionate 200 mcg total daily dose in adults with persistent asthma, twice-daily dosing (100 mcg BID) is superior to once-daily dosing (200 mcg QD) and should be the preferred regimen.

Evidence Against Once-Daily Dosing

The most comprehensive analysis directly addressing this question found that once-daily fluticasone propionate dosing at 200 mcg was statistically indistinguishable from placebo in multiple randomized controlled trials 1. This FDA review of six clinical trials demonstrated that:

• Twice-daily dosing was numerically superior to once-daily dosing at the same nominal dose across all comparative studies for the primary endpoint of change in pre-dose FEV₁ 1
• In five of six trials, once-daily FP showed no statistical superiority over placebo 1
• The single trial showing benefit for once-daily dosing (at 500 mcg) demonstrated only half the effect size compared to twice-daily administration 1

Direct Head-to-Head Comparison

A specific study comparing FP 100 mcg BID versus FP 200 mcg QD in both bronchodilator-only patients and inhaled corticosteroid-dependent patients revealed critical differences 2:

In patients previously on inhaled corticosteroids:

• FP 100 mcg BID increased FEV₁ by 0.27 L from baseline 2
• FP 200 mcg QD increased FEV₁ by only 0.11 L 2
• FP 100 mcg BID improved morning peak flow by 18 L/min versus a decrease of 3 L/min with once-daily dosing 2
• Withdrawal rates due to inadequate asthma control were 18% with BID dosing versus 32% with QD dosing 2

In bronchodilator-only patients:

• Both regimens showed more comparable efficacy, though BID remained numerically superior (0.49 L vs 0.37 L FEV₁ improvement) 2

Clinical Algorithm for Dosing Decision

Use twice-daily fluticasone propionate 100 mcg BID rather than 200 mcg QD because:

• Superior pulmonary function improvements with more consistent drug levels throughout the 24-hour period 2, 1
• Lower treatment failure rates and better asthma stability, particularly in patients stepping down from higher ICS doses 2
• No safety advantage demonstrated with once-daily dosing to justify the reduced efficacy 1
• No adherence benefit observed with once-daily versus twice-daily administration 1

Important Caveats

The evidence comparing fluticasone furoate (FF) once-daily to fluticasone propionate twice-daily is not applicable here, as these are different corticosteroid molecules with different pharmacokinetic profiles 3, 4. Fluticasone furoate was specifically designed for once-daily dosing with a 24-hour duration of action, whereas fluticasone propionate has a shorter duration requiring twice-daily administration for optimal effect 4.

The FDA specifically did not approve once-daily dosing for fluticasone propionate 100-200 mcg based on this evidence 1.