Efficacy of Loratadine Compared with Fexofenadine or Placebo for the Treatment of Seasonal Allergic Rhinitis

Harold B. Kaiser, Clinical Research Institute, Minneapolis, Minnesota, USA; Anthony Rooklin, Allergy Research Associates, Media, Pennsylvania, USA; Dennis Spangler, Atlanta Allergy & Immunology Research Foundation, Atlanta, Georgia; David Capano, Integrated Therapeutics Group, Inc., New Jersey, USA

Clin Drug Invest. 2001;21(8) 

In This Article

Abstract and Introduction

Objective: To compare loratadine with fexofenadine and placebo in relieving symptoms of seasonal allergic rhinitis (SAR).
Design: A randomised, double-blind, double-dummy, placebo-controlled, parallel-group study.
Study Participants: Participants were aged 12 to 60 years with spring/summer SAR and total symptom severity scores (TSS) of at least 8 (maximum score 15) on six of 14 pre-baseline time-points.
Interventions: Loratadine 10mg once daily, fexofenadine 60mg twice daily, or placebo for 7 days.
Main Outcome Measures and Results: The primary end-point was the reduction from baseline in am and pm reflective and instantaneous TSS at final assessment. Times to 25% and maximum reductions in am reflective TSS were also analysed. Drug administration with either loratadine or fexofenadine provided significant relief versus placebo: both agents provided similar reductions from baseline in am and pm reflective and instantaneous TSS at final assessment. Compared with fexofenadine, loratadine demonstrated a statistically greater percentage reduction in am and pm reflective TSS in four of the initial five assessments (p < 0.05 for day 1 pm, day 2 pm, and day 3 am and pm assessments), achieving significance versus fexofenadine as early as 12 hours following the first dose (day 1 pm). Median times to a 25% reduction and maximum reduction in am reflective TSS also occurred significantly earlier in patients receiving loratadine.
Conclusions: Compared with placebo, both loratadine and fexofenadine provided significant relief of the symptoms of SAR. At the first assessment following the first dose, however, loratadine demonstrated a significant reduction from baseline in TSS compared with fexofenadine. In addition, time-to-event analysis indicated that the reduction in symptoms occurred significantly earlier with loratadine.

Allergic rhinitis (AR) affects up to 40 million people in the United States annually and is associated with nasal and non-nasal symptoms that are bothersome and can negatively influence physical, psychological and social well-being.[1] AR is responsible for lost productivity[1] and sleep disturbances, it may impair learning,[2,3] and it is associated with more than 2 million missed school days each year.[4] The financial consequences of AR are considerable.

Antihistamines are considered first-line therapy for AR. To treat their symptoms, individuals with AR will frequently self-medicate with older, non-prescription antihistamines.[1] Although the older antihistamines are useful, their duration of action is generally short,[5] unless manufactured in a sustained-release form, and they are associated with anticholinergic effects and with sedation, due in part to their ability to readily penetrate the blood-brain barrier. Newer, second-generation, selective H1-receptor antagonists such as loratadine and fexofenadine offer benefits over older anti-histamines: they have an intrinsically longer duration of action, fewer anticholinergic effects, and do not readily penetrate the blood-brain barrier. Newer antihistamines have a rapid onset of action, providing relief within hours of administration,[6] a particular advantage because these agents are often taken in response to the symptoms of AR on an as-needed basis.

Loratadine is a selective peripheral H1-receptor antagonist administered once daily for full 24-hour relief of symptoms of seasonal AR (SAR). Loratadine is nonsedating, with poor penetration across the blood-brain barrier, resulting in a favourable central nervous system tolerability profile, and is indicated for the relief of the nasal and non-nasal symptoms of SAR.[7] Fexofenadine, a metabolite of terfenadine, is a nonsedating, H1-receptor antagonist with twice-daily administration (or once daily at a dose 50% greater than when administered twice daily) that is indicated for symptomatic relief of SAR.[8] The primary objective of this study was to compare loratadine with fexofenadine and placebo in reducing SAR symptoms.