Antihistamines are core treatments for allergic rhinitis, allergic conjunctivitis, and related conditions. The second‑generation H1‑receptor antagonists azelastine and levocabastine are used as intranasal sprays and ocular formulations to reduce histamine‑mediated symptoms. While randomized trials establish efficacy and common tolerability profiles, post‑marketing surveillance using large real‑world datasets can identify additional or differing adverse drug reaction (ADR) patterns not fully apparent in pre‑marketing studies.
This study performed a retrospective descriptive analysis of spontaneously reported ADRs for azelastine and levocabastine in the WHO VigiAccess database to compare reporting patterns, summarize the most frequently reported system‑organ class (SOC) events, and highlight drug‑specific differences that may aid clinicians in individualized prescribing.
The analysis used ADR reports available in WHO VigiAccess for the two antihistamines of interest. The dataset included global spontaneous reports and captured patient demographics (age, sex, geographic location) where available, together with ADR coding by system‑organ class and preferred terms. The investigators calculated reporting percentages for SOC categories for each drug and conducted a descriptive comparison of the ADR profiles between azelastine and levocabastine.
Both drugs are second‑generation H1 antagonists: azelastine is a phthalazinone derivative with additional inhibitory effects on various mediators of allergic inflammation, and levocabastine is a selective, long‑acting H1 antagonist used in nasal and ocular routes. The authors used disproportionate analyses within VigiAccess to explore ADR signals and sought ADRs not described in product labeling; specific statistical thresholds for disproportionate analysis were not detailed in the summary provided here.
Across the study period, a total of 11,592 adverse event reports linked to azelastine and levocabastine were identified in the VigiAccess database. When aggregated by SOC, the top five reported categories across both drugs were:
Comparative reporting patterns showed that azelastine had a higher proportion of reports categorized under Nervous system disorders. Levocabastine demonstrated relatively higher reporting proportions for endocrine disorders, injury/poisoning/procedural complications, and Nervous system disorders compared with azelastine. The authors note that SOC‑level ADRs exceeding 10% incidence were observed in 2 SOCs for azelastine and in 4 SOCs for levocabastine.
The study included tables and figures (referenced in the source article) detailing drug structures, indications, SOC distributions, and additional breakdowns; these are reported in the original manuscript.
The descriptive findings indicate that both intranasal/ocular second‑generation antihistamines are associated with a spectrum of reported ADRs in the real‑world VigiAccess database. General disorders and administration site conditions predominated, consistent with local administration routes and known topical effects. Substantial reporting of Nervous system disorders aligns with recognized central nervous system effects that, while typically less pronounced for second‑generation agents than first‑generation antihistamines, remain detectable in pharmacovigilance datasets.
Differences in SOC reporting patterns between azelastine and levocabastine suggest drug‑specific safety signal profiles that may influence clinical choice, particularly when patient comorbidities or concomitant medications raise concern for certain ADR categories. The authors emphasize that spontaneous reporting systems like VigiAccess provide important post‑marketing surveillance but are subject to limitations including underreporting, variable report quality and completeness, and reporting bias. These factors prevent direct incidence calculations or causal attribution solely from this dataset.
The study was positioned to detect signals and inform clinicians rather than to establish definitive comparative safety estimates. Full interpretation requires access to the detailed tables and figures in the published article and, ideally, complementary studies using controlled observational designs or pooled safety data.
Review of WHO VigiAccess reports for azelastine and levocabastine identified 11,592 related adverse event reports and highlighted common SOCs such as General disorders, Nervous system disorders, Gastrointestinal and Respiratory disorders. The two drugs showed both overlapping and distinct ADR reporting patterns, with azelastine linked to a higher proportion of nervous system reports and levocabastine showing higher proportions in several SOCs including endocrine and injury/poisoning categories. The authors recommend that clinicians be aware of these reported ADR patterns when selecting antihistamine therapy and consider real‑world safety signals alongside clinical efficacy and individual patient factors.
Note: The original article contains the complete dataset, tables, and figures referenced here; specific subgroup breakdowns and statistical details are available in the publication.