| アブストラクト | BACKGROUND: There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in '90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines. AIM: To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries. METHODS: We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases >/=3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance. RESULTS: Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible. CONCLUSIONS: Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by analytical studies is required, regulators and clinicians should consider risk-minimisation activities. Also antihistamines without signal but with peculiar use in a few Countries (e.g., levocetirizine) or with increasing consumption (e.g., rupatadine) deserve careful surveillance. |
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| ジャーナル名 | PloS one |
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| Pubmed追加日 | 2015/3/19 |
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| 投稿者 | Poluzzi, Elisabetta; Raschi, Emanuel; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio |
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| 組織名 | Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of;Bologna, Bologna, Italy.;Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden;;Strathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde;University, Glasgow, United Kingdom.;Clinical Pharmacology Unit, University of Verona, Verona, Italy.;Republic Fund for Health Insurance, Belgrade, Serbia.;Centre for Pharmacoepidemiology, Karolinska University Hospital, Solna,;Stockholm, Sweden; Stockholm, County Council, Stockholm, Sweden.;Erasmus University Medical Centre, Rotterdam, Netherlands. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/25785934/ |
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