Allergy-Like Immediate Reactions with Herbal Medicines: A Retrospective Study Using Data from VigiBase(®)

INTRODUCTION Herbal medicines are used worldwide and with an increasing popularity in Western countries. Although often perceived as 'naturally safe', herbals may cause severe adverse drug reactions (ADRs), with immediate allergic reactions being particularly life threatening. OBJECTIVES The aim of this study was to analyse immediate allergy-like ADRs to herbals documented in VigiBase(®), the WHO international pharmacovigilance database. METHODS The documentation of all suspected ADRs in association with herbal exposure reported to VigiBase(®) from 1969 to August 2014 was retrieved. Among all reports in which WHO-ART reaction terms were indicative of acute allergic reactions, those classified as 'suspect' with a documented causality assessment and latency time of ≤1 day were selected. For the most frequent specific herbal-ADR combinations, the information component (IC) as a measure of disproportionality based on Bayesian statistics was calculated. RESULTS We identified 757 reports out of 1039 ADRs. Products with mixed herbals (36.0 %) as well as those administered orally (63.2 %) were predominant. The most frequent reactions were urticaria and rash (49.2 %). Anaphylactic reactions accounted for 9.5 %. Disproportionally frequent reporting of mouth edema (IC = 1.81) and anaphylactic reactions (IC = 1.24) to Phleum pretense were noted. CONCLUSION Our findings indicate that herbal medicines for oral use carry a risk of causing immediate allergy-like ADRs. Studies using the Vigibase(®) database can identify specific combinations of particular herbs and adverse reactions. Healthcare professionals and patients should be aware of these risks and report any serious adverse experiences

Use of measures of disproportionality in pharmacovigilance:three Dutch examples

Spontaneous reporting systems for suspected adverse drug reactions (ADRs) remain a cornerstone of pharmacovigilance. In The Netherlands 'the Netherlands Pharmacovigilance Foundation Lareb' maintains such a system. A primary aim in pharmacovigilance is the timely detection of either new ADRs or a change of the frequency of ADRs that are already known to be associated with the drugs involved, i.e. signal detection. Adequate signal detection solely based on the human intellect (case by case analysis or qualitative signal detection) is becoming time consuming given the increasingly large number of data, as well as less effective, especially in more complex associations such as drug-drug interactions, syndromes and when various covariates are involved. In quantitative signal detection measures that express the extent in which combinations of drug(s) and clinical event(s) are disproportionately present in the database of reported suspected ADRs are used to reveal associations of interest. Although the rationale and the methodology of the various quantitative approaches differ, they all share the characteristic that they express to what extent the number of observed cases differs from the number of expected cases. In this paper three Dutch examples are described in which a measure of disproportionality is used in quantitative signal detection in pharmacovigilance: (i) the association between antidepressant drugs and the occurrence of non-puerpural lactation as an example of an association between a single drug and a single event; (ii) the onset or worsening of congestive heart failure associated with the combined use of nonsteroidal anti-inflammatory drugs and diuretics as an example of an association between two drugs and a single event (drug-drug interaction); and the (iii) (co)-occurrence of fever, urticaria and arthralgia and the use of terbinafine as an example of an association between a single drug and multiple events (syndrome). We conclude that the use of quantitative measures in addition to qualitative analysis is a step forward in signal detection in pharmacovigilance. More research is necessary into the performance of these approaches, especially its predictive value, its robustness as well as into further extensions of the methodology

Cyclooxygenase selectivity and chemical groups of non-steroidal anti-inflammatory drugs and the frequency of reporting hypersensitivity reactions: a case/non-case study in VigiBase

The reporting of hypersensitivity reactions (HSRs) among non-steroidal anti-inflammatory drugs (NSAIDs) according to cyclooxygenase (COX) selectivity and chemical groups has not been published yet in one study. This study assessed the reporting frequency of HSRs for NSAIDs based on their relative inhibitory potency towards COX enzymes and chemical groups, including the presence/absence of a functional sulfonamide group, in strata of 5 years after market authorization. A case/non-case study was performed among Individual Case Safety Reports (ICSRs) with NSAIDs as suspected drugs in VigiBase, the WHO spontaneous reporting database. Cases were ICSRs mentioning angioedema and anaphylactic/anaphylactoid shock conditions, while non-cases were ICSRs without HSRs. NSAIDs were categorized into (i) NSAIDs with highly COX-2 selectivity (coxibs), (ii) Non-coxib NSAIDs with COX-2 preference, (iii) NSAIDs with poor selectivity, or (iv) NSAIDs with unknown selectivity. Chemical groups were defined based on the Anatomical Therapeutic Chemical classification system and the presence/absence of a functional sulfonamide group. Reporting odds ratios (RORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression analysis. We identified 13,229 cases and 106,444 non-cases. In the first 5 years after marketing, poor selectivity NSAIDs and acetic acid derivatives were associated with the highest ROR of HSRs (age- and sex-adjusted ROR 2.12, 95%CI: 1.98-2.28 and ROR 2.21, 95%CI: 1.83-2.66, respectively), all compared to coxibs, and also sulfonamide NSAIDs compared to non-sulfonamide NSAIDs (age- and sex-adjusted ROR 1.38, 95%CI: 1.29-1.47). After the first 5 years of marketing, most of the RORs returned to approximately 1. This article is protected by copyright. All rights reserved