Data mining in FAERS: association of newer-generation H1-antihistamines with nervous system disorders

Background: H1-antihistamines are widely used to treat symptoms depending on histamine release in a variety of conditions. However, neurological adverse events have been reported in post-marketing surveillance studies and there are limited literatures comparing the neurological disorders associated with newer-generation H1-antihistamines from real-world datasets.

Aims: We performed a comparative analysis of nervous system disorders and several newer-generation H1-antihistamines including: cetirizine, loratadine, levocetirizine, desloratadine and fexofenadine.

Methods: Disproportionality analysis was used to identify the suspected drug neurological adverse events associated with H1-antihistamines of interest via the Food and Drug Administration Adverse Event Reporting System. The proportional reporting ratio (PRR), χ² (chi-square) and the reporting odds ratio (ROR) with 95% confidence interval (CI) were used to estimate the association.

Results: AE reports of 43,815 cases from 2017 to 2021 were extracted from FAERS. The H1-antihistamines included in our study were associated with various neurological adverse events that could be classified into 12 aspects, containing 42 preferred terms. The majority of adverse event reports were concentrated at somnolence: cetirizine [N = 1342, ROR (95%CI) = 11.8 (11.2-12.5), PRR = 10.8, χ² = 11755.4], levocetirizine [N = 1276, ROR(95%CI) = 28.5 (26.7-30.3), PRR = 22.7, χ² = 26218.4], loratadine[N = 516, ROR(95%CI) = 4.6 (4.2-5.0), PRR = 4.4, χ² = 1378.1], desloratadine [N = 33, ROR(95%CI) = 6.1 (4.3-8.6), PRR = 5.8, χ² = 131.9], fexofenadine [N = 498, ROR(95%CI) = 5.0 (4.6-5.5), PRR = 4.8, χ² = 1519.0].

Conclusion: Neurological AEs associated with individual newer generation H1-antihistamines of interest varies a lot, whereas somnolence was the most common AE reports. Fexofenadine was highly associated with headaches. Sedative effects associated with levocetirizine and cetirizine should arouse more concern. Seizures significantly associated with levocetirizine and desloratadine were infrequently reported, further research is needed to avoid possible serious outcomes. Patients taking cetirizine probably have higher risk of dystonia and anticholinergic syndrome.