Central Nervous System Effects of the Second-Generation Antihistamines Marketed in Japan -Review of Inter-Drug Differences Using the Proportional Impairment Ratio (PIR)-

Abstract

BackgroundSecond-generation antihistamines (AHs) have, in general, fewer sedative effects than the first-generation. However, important inter-drug differences remain in the degree of cognitive and/or psychomotor impairment. The extent to which a particular compound causes disruption can be conveniently compared, to all other AHs, using the Proportional Impairment Ratio (PIR). Although the PIR can differentiate the relative impairment caused by individual drugs, there is no indication of the reliability of the ratios obtained.ObjectiveTo calculate the PIRs –together with 95% confidence intervals (CIs), as an index of reliability– and compare AHs currently, or soon to be, available in Japan, with respect to their intrinsic capacity to cause impairment.MethodsResults from studies of cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mequitazine, and olopatadine were included in the PIR calculations. All data utilised came from crossover studies in healthy volunteers which were randomised and placebo and positive-internal controlled. Existing databases from studies reporting the sedative effects of AHs on objective (speed, accuracy, memory) and subjective (feeling) psychometrics were augmented, via results from suitable studies published after the previous reviews. The null value for a PIR was one.ResultsA total of 45 studies were finally included for this review. Of the AHs assessed, fexofenadine, ebastine, and levocetirizine showed a PIR for objective tests of 0. However, only fexofenadine (PIR = 0.49) had an upper limit of the 95% CI of less than 1. Fexofenadine, levocetirizine, desloratadine, olopatadine, loratadine, and mequitazine all had a PIR for subjective ratings of 0, but the upper limits of the 95% CIs were all in excess of 1, although fexofenadine (PIR = 2.57) was the lowest.ConclusionsThe results show that there are differences between second-generation AHs in the extent of sedation produced. However, subjective ratings indicate that patients may not necessarily be aware of this.

A simulated car‐driving study on the effects of acute administration of levocetirizine, fexofenadine, and diphenhydramine in healthy Japanese volunteers

“…These results suggest that it is safe to drive a car when taking levocetirizine 5 mg once daily. The present results seem to agree with a recent meta‐analysis using the proportional impairment ratio (PIR), where the PIRs for both objective and subjective measures were 0.0 for levocetirizine, while those with cetirizine were 6.38 for the subjective measure and 1.31 for the objective measure (Isomura et al, ).…”

On-the-road driving performance after use of the antihistamines mequitazine and l-mequitazine, alone and with alcohol

“…Newer, second-generation antihistamines penetrate the brain to a lower extent, due to their physico-chemical properties (Passalacqua et al, 1996 ; Tashiro et al, 2002 ). Therefore, these produce minor or no impairment on tests measuring memory, attention, psychomotor performance (Kay and Harris, 1999 ) and on-the-road driving, when given in the recommended dose (Isomura et al, 2014 ; Theunissen et al, 2009 ).…”

Antihistamines in Atopic Dermatitis Therapy

“…Only fexofenadine (Proportional Impairment Ratio= 0.49) had an upper limit of the 95% confidence intervals of less than 1. Fexofenadine, Levocetirizine, Desloratadine, Olopatadine, Loratadine, and Mequitazine all had a Proportional Impairment Ratio for subjective ratings of 0, but the upper limits of the 95% confidence intervals .The results showed that there were differences between antihistamine in the extent of sedation produced [40].…”