Fluticasone Reverses Oxymetazoline-induced Tachyphylaxis of Response and Rebound Congestion

RATIONALE: Chronic use of intranasal decongestants, such as oxymetazoline, leads to tachyphylaxis of response and rebound congestion, caused by alpha-adrenoceptor mediated down-regulation and desensitization of response. OBJECTIVES: We evaluated if tachyphylaxis can be reversed by intranasal fluticasone propionate, and the relative alpha(1)- and alpha(2)-adrenoceptor components of tachyphylaxis using the alpha(1)-antagonist prazosin. METHODS: In a randomized, double-blind, placebo-controlled, crossover design, 19 healthy subjects received intranasal oxymetazoline, 200 microg three times a day for 14 days, followed by the addition of fluticasone, 200 microg twice a day for a further 3 days. At Days 1, 14, and 17, participants received a single dose of oral prazosin, 1 mg, 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 versus Day 1, inspiratory flow decreased (mean difference, 95% confidence interval) (-47.9 L x min(-1); -63.9 to -31.9; P < 0.001) and the DRC shifted downward (24.8 L x min(-1); 20.3-29.3; P < 0.001). On Day 17 versus Day 14, after fluticasone, inspiratory flow increased (45 L x min(-1); 30-61; P < 0.001) and the DRC shifted upward (26.2 L x min(-1); 21.7-30.7; P < 0.001). On Day 1, prazosin reduced inspiratory flow (-52.6 L x min(-1); -19.2 to -86) compared with baseline. This effect was abolished on Day 14 (7.9 L x in(-1); -41.3 to 25.5). CONCLUSIONS: Oxymetazoline-induced tachyphylaxis and rebound congestion are 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 trial registered with www.clinicaltrials.gov (NCT 00487032).