ArticleDrug safety2008
Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs: the role of the aromatic ring.
Article in Drug safety, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 45 citations in OpenAlex.
- Association BetweenPharmaceuticals (Basel, Switzerland) · 2025Article
- Drug hypersensitivity reactions in children in clinical practice: A WAO Statement.The World Allergy Organization journal · 2025Review
- Evaluation of risk factors for recurrence of cutaneous adverse reactions due to anti-seizure medications in children: A retrospective study.Current journal of neurology · 2023Article
- Adverse Skin Reactions with Antiepileptic Drugs Using Korea Adverse Event Reporting System Database, 2008-2017.Journal of Korean medical science · 2020Article
- HLA-BFrontiers in neurology · 2019Article
- Chemistry-Wide Association Studies (CWAS): A Novel Framework for Identifying and Interpreting Structure-Activity Relationships.Journal of chemical information and modeling · 2018Article
- Cheminformatics-aided pharmacovigilance: application to Stevens-Johnson Syndrome.Journal of the American Medical Informatics Association : JAMIA · 2016Article
- Use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to Help Predict the Occurrence of Idiosyncratic Cutaneous Adverse Drug Reactions Associated with Antiepileptic Drug Usage.The AAPS journal · 2016Article
- Levetiracetam induced psoriasiform drug eruption: a rare case report.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2015Article
- PharmGKB summary: very important pharmacogene information for human leukocyte antigen B.Pharmacogenetics and genomics · 2015Article
- Risk factors for seizures and antiepileptic drug-associated adverse effects in high-grade glioma patients: A multicentre, retrospective study in Hong Kong.Surgical practice · 2015Article
- Pharmacokinetic of antiepileptic drugs in patients with hepatic or renal impairment.Clinical pharmacokinetics · 2014Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAntiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can explain symptoms of hypersensitivity.
methodsBetween January 1985 and January 2007, all adverse drug reactions (ADRs) reported to the Netherlands Pharmacovigilance Centre Lareb related to AEDs as suspected drugs were included in this study. ADRs were analysed using a case/non-case design. Cases were defined as those patients with ADRs involving symptoms of hypersensitivity. Non-cases were patients with all other ADR reports. Symptoms of hypersensitivity were classified according to the Gell and Coombs classification (type I-IV) and the organ involved (e.g. cutaneous, hepatic). AEDs were classified as aromatic anticonvulsant if their chemical structure contained at least one aromatic ring. All other AEDs were classified as non-aromatic. We assessed the strength of the association between aromatic AEDs versus non-aromatic AEDs and reported hypersensitivity reactions with logistic regression analysis and expressed these as reporting odds ratios (RORs).
resultsIn total, 303 cases of hypersensitivity associated with the use of AEDs were reported. Aromatic AEDs were suspected in 64.4% of these reports versus 41.3% (574/1389) of the non-hypersensitivity reports. A significant ROR of 2.15 (95% CI 1.63, 2.82) was found for aromatic AEDs and all hypersensitivity reactions. Aromatic AEDs were significantly associated with immunoglobin E-mediated type I hypersensitivity reactions (ROR 2.15; 95% CI 1.23, 3.78) and T-cell-mediated type IV reactions (ROR 6.06; 95% CI 3.41, 10.75). Type II and III reactions did not show an association. Cutaneous symptoms represented 39.9% of the hypersensitivity-related ADRs. Aromatic AEDs were significantly associated with cutaneous hypersensitivity reactions (ROR 5.81; 95% CI 3.38, 9.99).
conclusionThis study confirms that the presence of an aromatic ring as a common feature in chemical structures of AEDs partly explains apparent 'idiosyncratic' hypersensitivity reactions. Symptoms of hypersensitivity were reported twice as frequently with aromatic AEDs than with non-aromatic AEDs. Strong associations for aromatic AEDs versus non-aromatic AEDs were found for T-cell-mediated (type IV) reactions, as well as for cutaneous reactions.
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