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,☆☆

https://doi.org/10.1016/S0091-6749(99)70070-9Get rights and content

Abstract

Background: Fexofenadine hydrochloride (HCl) is a new H 1 antihistamine used twice daily in some countries. Objective: A multicenter, double-blind, parallel-group, placebo-controlled trial compared the efficacy and safety of fexofenadine HCl (120 and 180 mg administered once daily) and cetirizine (10 mg once daily) in the treatment of seasonal allergic rhinitis. Methods: After a 3- to 5-day run-in period, patients meeting entrance criteria were randomized to receive placebo, fexofenadine HCl 120 mg once daily, fexofenadine HCl 180 mg once daily, or cetirizine 10 mg once daily (active control) for 2 weeks. Eight hundred twenty-one patients comprised the intention-to-treat population and 722 patients completed the study. Symptom assessments were conducted 12 hours after the dose for the previous 12 hours and again at 24 hours after the dose for the previous 12 hours. In addition, assessment was made immediately before dosing in the morning for the previous 30 minutes. Total symptom score was calculated as the sum of scores for the 4 individual symptoms: (1) sneezing, (2) rhinorrhea, (3) itchy nose, palate, or throat, and (4) itchy, watery, or red eyes; the nasal congestion score was also recorded. Results: Both doses of fexofenadine HCl were superior to placebo in reducing the total symptom score. Efficacy was maintained for the entire dosing interval (ie, for 24 hours). There were no differences in efficacy between the 2 doses of fexofenadine HCl or between either dose of fexofenadine HCl and cetirizine. There was no major side effect, but the combined incidence of drowsiness or fatigue was greater with ce-tirizine (9%) than with placebo (4%) (P = .07) or fexofenadine (4%) (P = .02). Conclusions: Once-daily fexofenadine is thus a valuable addition to the nonsedating group of H 1 receptor antagonists currently available for the treatment of seasonal allergic rhinitis. (J Allergy Clin Immunol 1999;104:927-33.)

Section snippets

Study design

The study was a multicenter, double-blind, randomized, placebo-controlled, parallel-group design of 2 weeks’ duration, preceded by a single-blind placebo run-in period of 3 to 5 days in symptomatic patients with SAR. To ensure entry at periods of pollen prevalence, the local pollen count was recorded in each region of entry with use of the local pollen count method and the study was conducted in the respective peak grass pollen seasons.

Patient population

Patients were eligible to participate in the study if they

Number of patients studied

A total of 1094 eligible patients were screened for entry to the study. Of these, 842 fulfilled the entry criteria and were randomized to double-blind treatment at 49 investigation sites (33 in Europe, 15 in South Africa, and 1 in Australia). The mean (±SD) number of patients per center was 17 (±25.1), with the number of patients at each center ranging from 1 to 68. There were 8 centers with fewer than 5 patients and 17 centers with 5 to 10 patients; country centers were pooled if they had 6 or

DISCUSSION

This study demonstrates that fexofenadine HCl 120 mg and 180 mg administered QD is an effective and safe treatment for SAR, with efficacy comparable to that of cetirizine for both doses. There were no statistical differences among any of the active treatments in any of the primary or secondary efficacy criteria. All active treatments were still effective at trough drug levels, just before repeat daily dosing, indicating 24-hour symptom relief. Analysis of individual symptoms identified

Acknowledgements

We thank Hoechst Marion Roussel for providing the fexofenadine HCl and sponsoring this project and UCB Pharma for providing the cetirizine used in this study. We thank the following investigators who participated in the trial:

Dr Packermann, Sunnyside, South Africa; Dr Adler, Ludwigshafen, Germany; Dr N. F. Alberts, Heidelberg, South Africa; Dr C. Bachert, Dusseldorf, Germany; Dr Bannert, Weil am Rhein, Germany; Dr Barrage, Lieven, France; Dr B. Bertrand, Goddine, Belgium; Dr Bestajovski,

References (22)

  • FER Simons et al.

    Peripheral H1-blockade effect of fexofenadine

    Ann Allergy Asthma Immunol

    (1997)
  • D Bernstein et al.

    Efficacy and safety of fexofenadine for seasonal allergic rhinitis

    Ann Allergy Asthma Immunol

    (1997)
  • PH Howarth et al.

    The influence of cetirizine on symptom generation and nasal eosinophilia in seasonal allergic rhinitis

    J Allergy Clin Immunol

    (1991)
  • PH. Howarth

    Cellular basis for allergic rhinitis

    Allergy

    (1995)
  • J Bousquet et al.

    Pathophysiology of allergic rhinitis

    Int Arch Allergy Immunol

    (1996)
  • PH Howarth et al.

    The nasal mast cell and rhinitis

    Clin Exp Allergy

    (1991)
  • C Lippert et al.

    Mass balance and pharmacokinetics of fexofenadine HCl in healthy, male volunteers

    Pharm Res

    (1995)
  • D Rampe et al.

    Effects of terfenadine and its metabolites on a delayed rectifier K+ channel cloned from human heart

    Mol Pharmacol

    (1993)
  • RL Woosley et al.

    Mechanism of the cardiotoxic actions of terfenadine

    JAMA

    (1993)
  • JA Hey et al.

    Comparative analysis of the cardiotoxicity proclivities of second generation antihistamines in an experimental model predictive of adverse clinical ECG effects

    Arzneimittelforschung

    (1996)
  • EA Bronsky et al.

    Effectiveness and safety of fexofenadine, a new nonsedating H1-receptor antagonist, in the treatment of fall allergies

    Allergy Asthma Proc

    (1998)
  • Cited by (183)

    • Pollen respiratory allergy: Is it really seasonal?

      2023, World Allergy Organization Journal
    • Diphenhydramine: Time to Move on?

      2022, Journal of Allergy and Clinical Immunology: In Practice
      Citation Excerpt :

      In wheal and erythema suppression studies, cetirizine was found to be superior to fexofenadine, with loratadine being the least potent.76 Despite having minor difference in pharmacokinetics and pharmacodynamics individually, the second-generation antihistamines may be regarded as equally efficacious for allergic rhinitis based on the results of randomized controlled trials.77-79 They have been recommended over first-generation antihistamines based on being more favorable from a risk/benefit standpoint.80

    • Unintentional cetirizine overdose causing anticholinergic syndrome

      2022, American Journal of Emergency Medicine
    View all citing articles on Scopus

    Reprint requests: Peter Howarth, MBBS, FRCP, Respiratory Cell and Molecular Biology Division, University Medicine, Level D, Centre Block, Southampton General Hospital, Southampton, SO16 6YD, United Kingdom.

    ☆☆

    0091-6749/99 $8.00 + 0  1/1/101791

    View full text