Sedative Effects of Levocetirizine: A Systematic Review and Meta-Analysis of Randomized Controlled Studies

Abstract

Introduction

As a substrate of P-glycoprotein, levocetirizine should not cause sedative effects. However, while cetirizine, a mixture of levocetirizine and dextrocetirizine, can slightly penetrate the blood brain barrier, the sedative effects of levocetirizine are still under study.

Objectives

The aim of this study was to investigate the sedative effects of levocetirizine.

Methods

An electronic literature search was performed using Medline and EMBASE from January 01, 2001 through August 6, 2015. Randomized controlled trials (RCTs) comparing levocetirizine with other antihistamines or placebo for patients with allergy and healthy subjects were selected. Primary outcome was risk ratio between levocetirizine and comparators. Secondary outcome was change in psychomotor speed. Data were pooled for meta-analysis using a fixed-effect model.

Results

Forty-eight studies of 18,014 patients met the inclusion criteria. When compared to placebo, levocetirizine produced modest sedative effects (RR: 1.67; 95% CI 1.17, 2.38). However, when compared to other second-generation antihistamines, sedative effects of levocetirizine did not differ (RR: 1.23; 95% CI 0.96, 1.58). In subgroup analysis, there was no difference between the sedative effects of levocetirizine and fexofenadine (RR: 1.7; 95% CI 0.59, 4.88), desloratadine (RR: 1.58; 95% CI 0.9, 2.77), loratadine (RR: 1.56; 95% CI 0.28, 8.56), bilastine (RR: 1.17; 95% CI 0.48, 2.84), olopatadine (RR: 1.09; 95% CI 0.81, 1.47), azelastine (RR: 0.19; 95% CI 0.01, 3.68) and rupatadine (RR: 1.47; 95% CI 0.14, 15.72). When compared to first-generation antihistamines, levocetirizine had less sedative effects and less change of reaction time (mean difference: −250.76 s; 95% CI −338.53, −162.98).

Conclusion

Levocetirizine has modest sedative effects with a risk ratio of 1.67 when compared with placebo. The sedative effects observed for levocetirizine are not different from other second-generation antihistamines.

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Authors contributions

Kornkiat Snidvongs: conception, development of protocol, study selection, data extraction, assessment of risk of bias, data analysis and interpretation, manuscript preparation. Kachorn Seresirikachorn: search strategy, study selection. Likhit Khattiyawittayakun: data extraction, assessment of risk of bias. Wirach Chitsuthipakorn: conception, development of protocol, critical review, final approval.

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Correspondence to Kornkiat Snidvongs.

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Funding sources for the study

This was an unfunded study.

Authors’ financial disclosures

Kornkiat Snidvongs received honoraria for speaking at symposia for Merck Sharp & Dohme, GlaxoSmithKline, Takeda, Sanofi Aventis.

Kachorn Seresirikachorn, Likhit Khattiyawittayakun, and Wirach Chitsuthipakorn have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. 1

Risk of bias graph: each risk of bias item presented as percentages across all included studies (EPS 28 kb)

Fig. 2

Risk of bias summary: each risk of bias item for each included study (EPS 27 kb)

Fig. 3

Funnel plot; risk of drowsiness: levocetirizine vs. other second-generation antihistaminesSE standard error, RR risk ratio (EPS 93 kb)

Fig. 4

Funnel plot; risk of drowsiness: levocetirizine vs. placebo SE standard error, RR risk ratio (EPS 529 kb)

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Snidvongs, K., Seresirikachorn, K., Khattiyawittayakun, L. et al. Sedative Effects of Levocetirizine: A Systematic Review and Meta-Analysis of Randomized Controlled Studies. Drugs 77, 175–186 (2017). https://doi.org/10.1007/s40265-016-0682-0

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Keywords

  • Risk Ratio
  • Allergic Rhinitis
  • Epworth Sleepiness Scale
  • Cetirizine
  • Loratadine