Fluticasone Reverses Oxymetazoline Induced Tachyphylaxis of Response and Rebound Congestion

American Journal of Respiratory and Critical Care Medicine (Mar 2010)
Clearie K, Khan F, Lipworth B, Vaidyanathan S, Williamson P

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RATIONALE: Chronic use of intranasal decongestants like oxymetazoline leads to tachyphylaxis of response and rebound congestion, due to alpha-adrenoceptor mediated down-regulation and desensitization of response OBJECTIVES: We evaluated if tachyphylaxis can be reversed by intranasal fluticasone propionate, as well as the relative alpha1-/alpha2-adrenoceptor components of tachyphylaxis using the alpha1-antagonist prazosin. METHODS: In a randomized, double-blind, placebo-controlled, crossover design, 19 healthy subjects received intranasal oxymetazoline 200Amicrog tid for 14 days, followed by addition of fluticasone 200Amicrog bid for a further 3 days. At day 1, 14 and 17, participants received a single dose of oral prazosin 1mg or placebo with measurements made before and 2 hours later.
MEASUREMENTS AND MAIN RESULTS: Outcomes evaluated were peak nasal inspiratory flow, nasal resistance, blood flow and oxymetazoline dose-response curve (DRC). On day 14 vs. day 1, inspiratory flow decreased (mean difference, 95% CI) (â 47.9 L.min(-1);, â63.9 to â31.9, P<.001), the DRC shifted downward (24.8 L.min-1, 20.3 to 29.3, P<.001). On day 17 vs. day 14, after fluticasone, inspiratory flow increased (45.0 L.min(-1), 30.0 to 61.0, P<.001), the DRC shifted upward (26.2 L.min(-1), 21.7 to 30.7, P<.001). On day 1, prazosin reduced inspiratory flow (â52.6 L.min(-1), â19.2 to â86.0) compared to baseline. This effect was abolished on day 14 (7.9 L.min-1, â41.3 to 25.5).
CONCLUSIONS: Oxymetazoline induced tachyphylaxis and rebound congestion is reversed by intranasal fluticasone. Further studies are indicated to evaluate if combination nasal sprays of decongestant and corticosteroid are an effective strategy to obviate tachyphylaxis and rebound in rhinitis. Clinical trials registration information available at www.clinicaltrials.gov, i.d. #NCT00487032.