Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with seasonal allergic rhinitis

      This paper is only available as a PDF. To read, Please Download here.


      Azelastine nasal spray and oral cetirizine are selective histamine H1-receptor antagonists that are approved in the United States for the treatment of seasonal allergic rhinitis (SAR).


      The objective of the present study was to compare the efficacy and tolerability of azelastine nasal spray administered at the recommended dosage of 2 sprays per nostril twice daily with those of cetirizine in the treatment of moderate to severe SAR.


      This multicenter, randomized, double-blind, parallel-group, 2-week comparative study was conducted during the 2004 fall allergy season in patients with moderate to severe SAR. After a 1-week placebo lead-in period, patients were randomized to receive azelastine nasal spray 2 sprays per nostril twice daily plus placebo tablets or cetirizine 10-mg tablets once daily plus a placebo saline nasal spray for the 2-week double-blind treatment period. The primary efficacy variables were (1) change from baseline to day 14 in the 12-hour reflective total nasal symptom score (TNSS), which combines scores for rhinorrhea, sneezing, itchy nose, and nasal congestion, and (2) onset of action, based on the instantaneous TNSS over 4 hours after the first dose of study drug. During the double-blind treatment period, patients recorded their symptom scores on diary cards twice daily (morning and evening). Patients aged ≥18 years also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at baseline and on day 14.


      Three hundred seven patients were randomized to treatment, and 299 completed 2 weeks of study treatment. The age of the population ranged from 12 to 74 years (mean, 35 years), 62.9% were female, and 69.6% were white. Over 2 weeks of treatment, both groups had significant improvements in the TNSS compared with baseline (P < 0.001). The overall change in TNSS was significantly greater with azelastine nasal spray compared with cetirizine (29.3% vs 23.0% improvement, respectively; P = 0.015). In terms of onset of action, azelastine nasal spray significantly improved the instantaneous TNSS compared with cetirizine at 60 and 240 minutes after the initial dose (both, P = 0.040). Scores on each domain of the RQLQ were significantly improved in both groups compared with baseline (P < 0.001); the overall RQLQ score was significantly improved with azelastine nasal spray compared with cetirizine (P = 0.049). Both treatments were well tolerated.


      In this 2-week study in patients with moderate to severe SAR, azelastine nasal spray was well tolerated and produced significantly greater improvements in TNSS and total RQLQ score compared with cetirizine.
      To read this article in full you will need to make a payment
      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Casale TB
        The interaction of azelastine with human lung histamine H1, beta, and muscarinic receptor-binding sites.
        J Allergy Clin Immunol. 1989; 83: 771-776
        • Shin MH
        • Baroody F
        • Proud D
        • et al.
        The effect of azelastine on the early allergic response.
        Clin Exp Allergy. 1992; 22: 289-295
        • Shinoda M
        • Watanabe N
        • Suko T
        • et al.
        Effects of anti-allergic drugs on substance P (SP) and vasoactive intestinal peptide (VIP) in nasal secretions.
        Am J Rhinol. 1997; 11: 237-241
        • Ito H
        • Nakamura Y
        • Takagi S
        • Sakai K
        Effects of azelastine on the level of serum interleukin-4 and soluble CD23 antigen in the treatment of nasal allergy.
        Arzneimittelforschung. 1998; 48: 1143-1147
        • Ciprandi G
        • Pronzato C
        • Passalacqua G
        • et al.
        Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: An antiallergic activity.
        J Allergy Clin Immunol. 1996; 98 ([published correction appears in J Allergy Clin Immunol. 1997;100:146]): 1088-1096
        • Wasserman SI
        Histamine and the preclinical pharmacology of cetirizine.
        Ann Allergy. 1987; 59 (Suppl): S1-S3
        • Cheria-Sammari S
        • Aloui R
        • Gormand F
        • et al.
        Leukotriene B4 production by blood neutrophils in allergic rhinitis—effects of cetirizine.
        Clin Exp Allergy. 1995; 25: 729-736
        • Charlesworth EN
        • Kagey-Sobotka A
        • Norman PS
        • Lichtenstein LM
        Effect of cetirizine on mast cell-mediator release and cellular traffic during the cutaneous late-phase reaction.
        J Allergy Clin Immunol. 1989; 83: 905-912
        • Ciprandi G
        • Buscaglia S
        • Pesce G
        • et al.
        Cetirizine reduces inflammatory cell recruitment and ICAM-1 (or CD54) expression on conjunctival epithelium in both early- and late-phase reactions after allergen-specific challenge.
        J Allergy Clin Immunol. 1995; 95: 612-621
        • Day JH
        • Briscoe M
        • Widlitz MD
        Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: Effects after controlled ragweed pollen challenge in an environmental exposure unit.
        J Allergy Clin Immunol. 1998; 101: 638-645
        • Day JH
        • Briscoe M
        • Rafeiro E
        • et al.
        Comparative onset of action and symptom relief with cetirizine, loratadine, or placebo in an environmental exposure unit in subjects with seasonal allergic rhinitis: Confirmation of a test system.
        Ann Allergy Asthma Immunol. 2001; 87: 474-481
        • Meltzer EO
        • Weiler JM
        • Widlitz MD
        Comparative outdoor study of the efficacy, onset and duration of action, and safety of cetirizine, loratadine, and placebo for seasonal allergic rhinitis.
        J Allergy Clin Immunol. 1996; 97: 617-626
        • Howarth PH
        • Stern MA
        • Roi L
        • et al.
        Double-blind, placebo-controlled study comparing the efficacy and safety of fexofenadine hydrochloride (120 and 180 mg once daily) and cetirizine in seasonal allergic rhinitis.
        J Allergy Clin Immunol. 1999; 104: 927-933
        • Hampel F
        • Ratner P
        • Mansfield L
        • et al.
        Fexofenadine hydrochloride, 180 mg, exhibits equivalent efficacy to cetirizine, 10 mg, with less drowsiness in patients with moderate-to-severe seasonal allergic rhinitis.
        Ann Allergy Asthma Immunol. 2003; 91: 354-361
        • Day JH
        • Briscoe MP
        • Rafeiro E
        • et al.
        Randomized double-blind comparison of cetirizine and fexofenadine after pollen challenge in the environmental exposure unit: Duration of effect in subjects with seasonal allergic rhinitis.
        in: Allergy Asthma Proc. 25. 2004: 59-68
        • Newson-Smith G
        • Powell M
        • Baehre M
        • et al.
        A placebo controlled study comparing the efficacy of intranasal azelastine and beclomethasone in the treatment of seasonal allergic rhinitis.
        Eur Arch Otorhinolaryngol. 1997; 254: 236-241
        • Charpin D
        • Godard P
        • Garay RP
        • et al.
        A multicenter clinical study of the efficacy and tolerability of azelastine nasal spray in the treatment of seasonal allergic rhinitis: A comparison with oral cetirizine.
        Eur Arch Otorhinolaryngol. 1995; 252: 455-458
        • Berger WE
        • White MV
        Efficacy of azelastine nasal spray in patients with an unsatisfactory response to loratadine.
        Ann Allergy Asthma Immunol. 2003; 91 (for the Rhinitis Study Group): 205-211
        • LaForce CF
        • Corren J
        • Wheeler WJ
        • Berger WE
        Efficacy of azelastine nasal spray in seasonal allergic rhinitis patients who remain symptomatic after treatment with fexofenadine.
        Ann Allergy Asthma Immunol. 2004; 93 (for the Rhinitis Study Group): 154-159
      1. Draft Guidance for Industry on Allergic Rhinitis: Clinical Development Programs for Drug Products. US Dept of Health and Human Services, Food and Drug Administration, Rockville, Md2000
        • Juniper EF
        • Guyatt GH
        • Andersson B
        • Ferrie PJ
        Comparison of powder and aerosolized budesonide in perennial rhinitis: Validation of Rhinitis Quality of Life Questionnaire.
        Ann Allergy. 1993; 70: 225-230
        • Corren J
        • Sacks H
        • Nayak A
        Efficacy of azelastine nasal spray, cetirizine tablets, fluticasone nasal spray, and placebo in patients with seasonal allergic rhinitis.
        Ann Allergy Asthma Immunol. 2005; 94 (Abstract): 197
        • Dykewicz MS
        • Fineman S
        • Skoner DP
        • et al.
        Diagnosis and management of rhinitis: Complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology.
        Ann Allergy Asthma Immunol. 1998; 81 (for the American Academy of Allergy, Asthma and Immunology): 478-518
        • Horak F
        • Stubner P
        • Zieglmayer R
        • et al.
        Controlled comparison of the efficacy and safety of cetirizine 10 mg o.d. and fexofenadine 120 mg o.d. in reducing symptoms of seasonal allergic rhinitis.
        Int Arch Allergy Immunol. 2001; 125: 73-79
        • Meltzer EO
        • Weiler JM
        • Dockhorn RJ
        • et al.
        Azelastine nasal spray in the management of seasonal allergic rhinitis.
        Ann Allergy. 1994; 72: 354-359
        • Weiler JM
        • Meltzer EO
        • Benson PM
        • et al.
        A dose-ranging study of the efficacy and safety of azelastine nasal spray in the treatment of seasonal allergic rhinitis with an acute model.
        J Allergy Clin Immunol. 1994; 94: 972-980
        • Juniper EF
        Measuring health-related quality of life in rhinitis.
        J Allergy Clin Immunol. 1997; 99: S742-S749
        • Georgitis JW
        Nasal hyperthemia and simple irrigation for perennial rhinitis. Changes in inflammatory mediators.
        Chest. 1994; 106: 1487-1492
        • Tomooka LT
        • Murphy C
        • Davidson IM
        Clinical study and literature review of nasal irrigation.
        Laryngoscope. 2000; 110: 1189-1193