A review of the efficacy of desloratadine, fexofenadine, and levocetirizine in the treatment of nasal congestion in patients with allergic rhinitis

  • Claus Bachert
    Address correspondence to: Claus Bachert, MD, PhD, Department of Otorhinolaryngology, University Hospital Ghent, De Pintelaan 185, BE-9000, Ghent, Belgium.
    Department of Otorhinolaryngology, University Hospital Ghent, Ghent, Belgium
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.


      Background: Nasal congestion is the most troublesome symptom of allergic rhinitis (AR). First-generation and older second-generation antihistamines, while effective against nasal itching, sneezing, and rhinorrhea, have limited efficacy in relieving nasal congestion.
      Objective: This review included nasal challenge studies and clinical trials that reported the effects on nasal congestion of the newer second-generation antihista-mines desloratadine, fexofenadine, and levocetirizine.
      Methods: MEDLINE and EMBASE were searched for nasal challenge studies and clinical trials published in English between January 1, 1991, and January 31, 2009, using the following terms, alone or in combination: antihistamines, second-generation antihistamines, allergic rhinitis, intermittent allergic rhinitis, perennial allergic rhinitis, persistent allergic rhinitis, seasonal allergic rhinitis, nasal challenge, nasal blockage, and nasal congestion. Studies that were not active or placebo controlled, that did not evaluate change in nasal congestion scores, or that focused on treatments other than desloratadine, fexofenadine, and levoce-tirizine for nasal congestion associated with AR were excluded.
      Results: Twenty-six clinical trials met the criteria for inclusion in the review. In 11 placebo-controlled trials that included objective assessment of nasal congestion, desloratadine, fexofenadine, and levocetiri-zine were associated with reductions in the severity of nasal congestion through maintenance of nasal airflow. The mean AUC for nasal airflow over 6 hours was significantly greater with desloratadine compared with placebo in 3 studies (P < 0.05); placebo-controlled trials of fexofenadine and levocetirizine had similar results. In 25 placebo- and active-controlled trials that reported subject-rated symptom scores, the 3 newer antihistamines were efficacious in the treatment of nasal congestion associated with AR. In 10 trials that reported objective and/or subjective measures, desloratadine was associated with significant improvements in nasal congestion compared with placebo (P ≤ 0.05), beginning as early as the first 2 hours after allergen challenge. Fexofenadine was associated with significantly lower nasal congestion scores compared with placebo in 4 studies (P <- 0.05); nasal congestion scores were significantly reduced with levocetirizine in 3 placebo-controlled trials (P ≤ 0.005).
      Conclusions: In the studies reviewed, desloratadine, fexofenadine, and levocetirizine were effective in relieving the nasal congestion associated with AR compared with placebo. This effect began as early as day 2 and was consistent and progressive throughout treatment. Desloratadine, fexofenadine, and levocetirizine are appropriate options for the treatment of nasal congestion in patients with AR.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Compalati E
        • Penagos M
        • Henley K
        • Canonica GW
        Allergy prevalence survey by the World Allergy Organization.
        Allergy Clin Immunol Int: J World Allergy Org. 2007; 19: 82-90
        • Sibbald B
        Epidemiology of allergic rhinitis.
        in: Burr ML Epidemiology of Clinical Allergy. Monographs in Allergy. Vol 31. Karger, Basel, Switzerland1993: 61-79
        • Juniper EF
        • Guyatt GH
        • Dolovich J
        Assessment of quality of life in adolescents with allergic rhinoconjunctivitis: Development and testing of a questionnaire for clinical trials.
        J Allergy Clin Immunol. 1994; 93: 413-423
        • Shedden A
        • Iezzoni D
        Congestion and its impact on sleep in individuals with allergic rhinitis.
        in: Presented at: 25th Congress of the European Academy of Allergology and Clinical Immunology, Vienna, AustriaJune 10–14, 2006
        • Shedden A
        Impact of nasal congestion on quality of life and work productivity in allergic rhinitis: Findings from a large online survey.
        Treat Respir Med. 2005; 4: 439-446
        • Bousquet J
        • van Cauwenberge P
        • Khaltaev N
        • the Aria Workshop Group and the World Health Organization
        Allergic rhinitis and its impact on asthma.
        J Allergy Clin Immunol. 2001; 108: S147-S334
        • Bousquet J
        • Khaltaev N
        • Cruz AA
        • et al.
        • the World Health Organization, GA(2)LEN, and AllerGen
        Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen).
        Allergy. 2008; 63: 8-160
        • Price D
        • Bond C
        • Bouchard J
        • et al.
        International Primary Care Respiratory Group (IPCRG) guidelines: Management of allergic rhinitis.
        Prim Care Respir J. 2006; 15: 58-70
        • Dykewicz MS
        • Fineman S
        • Skoner DP
        • et al.
        • the American Academy of Allergy, Asthma, and Immunology
        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: 478-518
        • Mahmoud F
        • Arifhodzic N
        • Haines D
        • Novotney L
        Levocetirizine modulates lymphocyte activation in patients with allergic rhinitis.
        J Pharmacol Sci. 2008; 108: 149-156
        • Vena GA
        • Cassano N
        • Buquicchio R
        • Ventura MT
        Anti-inflammatory effects of H1-antihistamines: Clinical and immunological relevance.
        Curr Pharm Des. 2008; 14: 2902-2911
      1. Clarinex (desloratadine) [package insert]. Schering-Plough Corporation, Kenilworth, NJ2007
      2. Allegra (fexofenadine hydrochloride) [package insert]. Sanofi-Aventis, Bridgewater, NJ2007
      3. Xyzal (levocetirizine dihydrochloride) [package insert]. UCB Pharma Inc, Smyrna, Ga2008
      4. Aerius (desloratadine) [package insert]. Schering-Plough Europe, Brussels, Belgium2006
      5. Telfast (fexofenadine hydrochloride) [package insert]. Sanofi-Aventis, Surrey, UK2007
      6. Xyzal (levocetirizine dihydrochloride) [package insert]. UCB Pharma Ltd, Berkshire, UK2008
        • Doyle WJ
        • Boehm S
        • Skoner DP
        Physiologic responses to intranasal dose-response challenges with histamine, methacholine, bradykinin, and prostaglandin in adult volunteers with and without nasal allergy.
        J Allergy Clin Immunol. 1990; 86: 924-935
        • Wang D
        • Smitz J
        • Waterschoot S
        • Clement P
        An approach to the understanding ofthe nasal early-phase reaction induced by nasal allergen challenge.
        Allergy. 1997; 52: 162-167
        • Taylor-Clark T
        • Sodha R
        • Warner B
        • Foreman J
        Histamine receptors that influence blockage of the normal human nasal airway.
        Br J Pharmacol. 2005; 144: 867-874
        • Baraniuk JN
        • Kim D
        Nasonasal reflexes, the nasal cycle, and sneeze.
        Curr Allergy Asthma Rep. 2007; 7: 105-111
        • White MV
        The role of histamine in allergic diseases.
        J Allergy Clin Immunol. 1990; 86: 599-605
        • Yang TQ
        • Takeuchi K
        • Hayashi S
        • Majima Y
        Effect of histamine on the permeability of the nasal mucosa in vivo.
        Acta Otolaryngol. 2003; 123: 401-405
        • Togias A
        Unique mechanistic features of allergic rhinitis.
        J Allergy Clin Immunol. 2000; 105: S599-S604
        • Wang D
        • Clement P
        • Smitz J
        • et al.
        Correlations between complaints, inflammatory cells and mediator concentrations in nasal secretions after nasal allergen challenge and during natural allergen exposure.
        Int Arch Allergy Immunol. 1995; 106: 278-285
        • Pearlman DS
        Pathophysiology of the inflammatory response.
        J Allergy Clin Immunol. 1999; 104: S132-S137
        • Terada N
        • Hamano N
        • Hohki G
        • et al.
        Late phase response in nasal mucosa closely correlated with immediate phase reaction and hyperreactivity to histamine.
        Acta Otolaryngol. 1998; 118: 392-397
        • Patou J
        • De Smedt H
        • van Cauwenberge P
        • Bachert C
        Pathophysiology of nasal obstruction and meta-analysis of early and late effects of levocetirizine.
        Clin Exp Allergy. 2006; 36: 972-981
        • Andersson M
        • Rimmer J
        • Salome C
        • et al.
        Dual symptomatic and exudative nasal responses are not characteristics of perennial allergic rhinitis.
        Acta Otolaryngol. 2001; 121: 407-413
        • Wang DY
        • Raza MT
        • Gordon BR
        Control of nasal obstruction in perennial allergic rhinitis.
        Curr Opin Allergy Clin Immunol. 2004; 4: 165-170
        • Holt PG
        Development of T-cell memory against inhalant allergies: Risks for the future.
        Clin Exp Allergy. 1999; 29: 8-13
        • Bush RK
        Etiopathogenesis and management of perennial allergic rhinitis: A state-of-the-art review.
        Treat Respir Med. 2004; 3: 45-57
        • Bellanti JA
        • Wallerstedt DB
        Allergic rhinitis update: Epidemiology and natural history.
        Allergy Asthma Proc. 2000; 21: 367-370
        • Kay AB
        Allergy and allergic diseases. First of two parts.
        N Engl J Med. 2001; 344: 30-37
        • Schroeder JT
        • Schleimer RP
        • Lichtenstein LM
        • Kreutner W
        Inhibition of cytokine generation and mediator release by human basophils treated with desloratadine.
        Clin Exp Allergy. 2001; 31: 1369-1377
        • Genovese A
        • Patella V
        • De Crescenzo G
        • et al.
        Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human Fc epsilon RI+ cells.
        Clin Exp Allergy. 1997; 27: 559-567
        • Lippert U
        • Krüger-Krasagakes S
        • Möller A
        • et al.
        Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist decarbo-ethoxyloratadine and dexamethasone by human mast and basophilic cell lines.
        Exp Dermatol. 1995; 4: 272-276
        • Holden NS
        • Gong W
        • King EM
        • et al.
        Potentiation of NF-kappaB-dependent transcription and inflammatory mediator release by histamine in human airway epithelial cells.
        Br J Pharmacol. 2007; 152: 891-902
        • Devillier P
        • Roche N
        • Faisy C
        Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexo fenadine and levocetirizine: A comparative review.
        Clin Pharmacokinet. 2008; 47: 217-230
        • Paakkari I
        Cardiotoxicity of new antihistamines and cisapride.
        Toxicol Lett. 2002; 127: 279-284
        • Ohmura T
        • Chachin M
        • Tarui S
        • et al.
        Effects of terfenadine, astemi-zole and epinastine on electrocardiogram in conscious cynomolgus monkeys.
        Eur J Pharmacol. 1999; 378: 169-175
        • Bachert C
        • van Cauwenberge P
        • Khaltaev N
        • the Allergic Rhinitis and its Impact on Asthma Workshop Expert Panel in collaboration with the World Health Organization
        Executive summary of the workshop report. 7–10 December 1999, Geneva, Switzerland [published correction appears in Allergy. 2002; 57:1208].
        Allergy. 2002; 57: 841-855
        • Zareba W
        • Moss AJ
        • Rosero SZ
        • et al.
        Electrocardiographic findings in patients with diphenhydramine overdose.
        Am J Cardiol. 1997; 80: 1168-1173
        • Golightly LK
        • Greos LS
        Second-generation antihistamines: Actions and efficacy in the management of allergic disorders.
        Drugs. 2005; 65: 341-384
        • Bousquet J
        • van Cauwenberge P
        • Aït Khaled N
        • et al.
        Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).
        Allergy. 2006; 61: 1086-1096
        • Simpson RJ
        Budesonide and terfenadine, separately and in combination, in the treatment of hay fever.
        Ann Allergy. 1994; 73: 497-502
        • Bronsky EA
        • Dockhorn RJ
        • Meltzer EO
        • et al.
        Fluticasone propionate aqueous nasal spray compared with terfenadine tablets in the treatment of seasonal allergic rhinitis.
        J Allergy Clin Immunol. 1996; 97: 915-921
        • Howarth PH
        • Emanuel MB
        • Holgate ST
        Astemizole, a potent hista-mine H1-receptor antagonist: Effect in allergic rhinoconjunctivitis, on antigen and histamine induced skin weal responses and relationship to serum levels.
        Br J Clin Pharmacol. 1984; 18: 1-8
        • Howarth PH
        • Holgate ST
        Comparative trial of two non-sedative H1 antihistamines, terfenadine and astemizole, for hay fever.
        Thorax. 1984; 39: 668-672
        • Wihl JA
        • Petersen BN
        • Petersen LN
        • et al.
        Effect of the nonsedative H1-receptor antagonist astemizole in perennial allergic and nonallergic rhinitis.
        J Allergy Clin Immunol. 1985; 75: 720-727
        • Rosenwasser LJ
        Treatment of allergic rhinitis.
        Am J Med. 2002; 113: 17S-24S
        • Berman BA
        Perennial allergic rhinitis: Clinical efficacy of a new anti-histamine.
        J Allergy Clin Immunol. 1990; 86: 1004-1008
        • Simons FE
        • Simons KJ
        H1 Receptor antagonist treatment of chronic rhinitis.
        J Allergy Clin Immunol. 1988; 81: 975-980
        • Horak F
        • Stübner 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
        • Scadding GK
        Clinical assessment of antihistamines in rhinitis.
        Clin Exp Allergy. 1999; 29: 77-81
        • Bachert C
        • Brostoff J
        • Scadding GK
        • et al.
        • the RIPERAN Study Group
        Mizolastine therapy also has an effect on nasal blockade in perennial allergic rhinoconjunctivitis.
        Allergy. 1998; 53: 969-975
        • Day JH
        • Horak F
        • Briscoe MP
        • et al.
        The role of allergen challenge chambers in the evaluation of antiallergic medication: An international consensus paper.
        Clin Exp Allergy Rev. 2006; 6: 31-59
        • Greiff L
        • Persson CG
        • Andersson M
        Desloratadine reduces allergen challenge-induced mucinous secretion and plasma exudation in allergic rhinitis.
        Ann Allergy Asthma Immunol. 2002; 89: 413-418
        • Horak F
        • Stübner P
        • Zieglmayer R
        • Harris AG
        Comparison of the effects of desloratadine 5-mg daily and placebo on nasal airflow and seasonal allergic rhinitis symptoms induced by grass pollen exposure.
        Allerg. 2003; 58: 481-485
        • Horak F
        • Stübner P
        • Zieglmayer R
        • Harris AG
        Effect of desloratadine versus placebo on nasal airflow and subjective measures of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure unit.
        J Allergy Clin Immunol. 2002; 109: 956-961
        • Lee DK
        • Gardiner M
        • Haggart K
        • et al.
        Comparative effects of desloratadine, fexofenadine, and levocetirizine on nasal adenosine monophosphate challenge in patients with perennial allergic rhinitis.
        Clin Exp Allergy. 2004; 34: 650-653
        • Ciprandi G
        • Cirillo I
        • Vizzaccaro A
        • et al.
        Desloratadine and levocetiriz-ine improve nasal symptoms, airflow, and allergic inflammation in patients with perennial allergic rhinitis: A pilot study.
        Int Immunopharmacol. 2005; 5: 1800-1808
        • Meltzer EO
        • Jalowayski AA
        • Vogt K
        • et al.
        Effect of desloratadine therapy on symptom scores and measures of nasal patency in seasonal allergic rhinitis: Results of a singlecenter, placebo-controlled trial.
        Ann Allergy Asthma Immunol. 2006; 96: 363-368
        • Vogt KF
        • Hasse W
        The clinical impact of high resolution rhinoma-nometry (HRR): Statistical analysis of 1417 cases.
        Clin Exp Allergy. 2001; 31 (Abstract 32): 1155
        • Nayak AS
        • Schenkel E
        Desloratadine reduces nasal congestion in patients with intermittent allergic rhinitis.
        Allergy. 2001; 56: 1077-1080
        • Meltzer EO
        • Prenner BM
        • Nayak A
        • the Desloratadine Study Group
        Efficacy and tolerability of oncedaily 5mg desloratadine, an H1-receptor antagonist, in patients with seasonal allergic rhinitis: Assessment during the spring and fall allergy seasons.
        Clin Drug Invest. 2001; 21: 25-32
        • Berger WE
        • Schenkel EJ
        • Mansfield LE
        • the Desloratadine Study Group
        Safety and efficacy of desloratadine 5 mg in asthma patients with seasonal allergic rhinitis and nasal congestion.
        Ann Allergy Asthma Immunol. 2002; 89: 485-491
        • Kim K
        • Sussman G
        • Hébert J
        • et al.
        Desloratadine therapy for symptoms associated with perennial allergic rhinitis.
        Ann Allergy Asthma Immunol. 2006; 96: 460-465
        • Berger WE
        • Lumry WR
        • Meltzer EO
        • Pearlman DS
        Efficacy of desloratadine, 5 mg, compared with fex-ofenadine, 180 mg, in patients with symptomatic seasonal allergic rhinitis.
        Allerg Asthma Proc. 2006; 27: 214-223
        • Wilson AM
        • Haggart K
        • Sims EJ
        • Lipworth BJ
        Effects of fexofenadine and desloratadine on subjective and objective measures of nasal congestion in seasonal allergic rhinitis.
        Clin Exp Allergy. 2002; 32: 1504-1509
        • Canonica GW
        • Tarantini F
        • Compalati E
        • Penagos M
        Efficacy of desloratadine in the treatment of allergic rhinitis: A meta-analysis of randomized, double-blind, controlled trials.
        Allergy. 2007; 62: 359-366
        • Casale TB
        • Andrade C
        • Qu R
        Safety and efficacy of once-daily fexofenadine HCl in the treatment of autumn seasonal allergic rhinitis.
        Allergy Asthma Proc. 1999; 20: 193-198
        • Ciprandi G
        • Cosentino C
        • Milanese M
        • et al.
        Fexofenadine reduces nasal congestion in perennial allergic rhinitis.
        Allerg. 2001; 56: 1068-1070
        • van Cauwenberge P
        • Juniper EF
        Comparison of the efficacy, safety and quality of life provided by fexofenadine hydrochloride 120 mg, loratadine 10 mg and placebo administered once daily for the treatment of seasonal allergic rhinitis.
        Clin Exp Allerg. 2000; 30: 891-899
        • Day JH
        • Briscoe MP
        • Rafeiro E
        • et al.
        Comparative efficacy of cetirizine and fexofenadine for seasonal allergic rhinitis, 5–12 hours postdose, in the environmental exposure unit.
        Allergy Asthma Proc. 2005; 26: 275-282
        • 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.
        Allergy Asthma Proc. 2004; 25: 59-68
        • 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
        • Terrien MH
        • Rahm F
        • Fellrath JM
        • Spertini F
        Comparison of the effects of terfenadine with fexofena-dine on nasal provocation tests with allergen.
        J Allergy Clin Immunol. 1999; 103: 1025-1030
        • Deruaz C
        • Leimgruber A
        • Berney M
        • et al.
        Levocetirizine better protects than desloratadine in a nasal provocation with allergen.
        J Allergy Clin Immunol. 2004; 113: 669-676
        • Day JH
        • Briscoe MP
        • Rafeiro E
        • Ratz JD
        Comparative clinical efficacy, onset and duration of action of levocetirizine and desloratadine for symptoms of seasonal allergic rhinitis in subjects evaluated in the Environmental Exposure Unit (EEU).
        Int J Clin Pract. 2004; 58: 109-118
        • Stübner P
        • Zieglmayer R
        • Horak F
        A direct comparison of the efficacy of antihistamines in SAR and PAR: Randomised, placebo-controlled studies with levocetirizine and loratadine using an environmental exposure unit-the Vienna Challenge Chamber (VCC).
        Curr Med Res Opin. 2004; 20: 891-902
        • Potter PC
        • the Study Group
        Levocetirizine is effective for symptom relief including nasal congestion in adolescent and adult (PAR) sensitized to house dust mites.
        Allergy. 2003; 58: 893-899
        • de Blic J
        • Wahn U
        • Billard E
        • et al.
        Levocetirizine in children: Evidenced efficacy and safety in a 6-week randomized seasonal allergic rhinitis trial.
        Pediatr Allergy Immunol. 2005; 16: 267-275
        • Bachert C
        • Bousquet J
        • Canonica W
        • et al.
        • the XPERT Study Group
        Levocetirizine improves quality of life and reduces costs in long-term management of persistent allergic rhinitis.
        J Allergy Clin Immunol. 2004; 114: 838-844
        • Meltzer EO
        • Kunjibettu S
        • Hall N
        • et al.
        Efficacy and safety of cicle-sonide, 200 microg once daily, for the treatment of perennial allergic rhinitis.
        Ann Allergy Asthma Immunol. 2007; 98: 175-181
        • Ratner PH
        • Wingertzahn MA
        • van Bavel JH
        • et al.
        Efficacy and safety of ciclesonide nasal spray for the treatment of seasonal allergic rhinitis.
        J Allergy Clin Immunol. 2006; 118: 1142-1148
        • Kaiser HB
        • Naclerio RM
        • Given J
        • et al.
        Fluticasone furoate nasal spray: A single treatment option for the symptoms of seasonal allergic rhinitis.
        J Allergy Clin Immunol. 2007; 119: 1430-1437
        • Patel D
        • Garadi R
        • Brubaker M
        • et al.
        Onset and duration of action of nasal sprays in seasonal allergic rhinitis patients: Olopatadine hydrochloride versus mometasone furoate monohydrate.
        Allergy Asthma Proc. 2007; 28: 529-592
        • Bende M
        • Carrillo T
        • Vóna I
        • et al.
        A randomized comparison of the effects of budesonide and mometasone furoate aqueous nasal sprays on nasal peak flow rate and symptoms in perennial allergic rhinitis.
        Ann Allergy Asthma Immunol. 2002; 88: 617-623