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Pro-arrhythmic potential of oral antihistamines (H1): combining adverse event reports with drug utilization data across Europe.

Poluzzi E, Raschi E, Godman B, Koci A, Moretti U, Kalaba M, Wettermark B, Sturkenboom M, De Ponti F - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Antihistamine utilisation on the basis of pharmacovigilance signals.
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pone.0119551.g002: Antihistamine utilisation on the basis of pharmacovigilance signals.

Mentions: Antihistamines with stronger signals represented a very different percentage of the total antihistamine utilization in each Country, e.g. ranging from 43% in Spain (Catalonia) to 97% in Croatia (Fig. 2). Among these, cetirizine was >29 DID in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia (Fig. 3). Drugs with weak signals accounted for no more than 10% (in Sweden) and in most Countries their use was negligible.


Pro-arrhythmic potential of oral antihistamines (H1): combining adverse event reports with drug utilization data across Europe.

Poluzzi E, Raschi E, Godman B, Koci A, Moretti U, Kalaba M, Wettermark B, Sturkenboom M, De Ponti F - PLoS ONE (2015)

Antihistamine utilisation on the basis of pharmacovigilance signals.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4364720&req=5

pone.0119551.g002: Antihistamine utilisation on the basis of pharmacovigilance signals.
Mentions: Antihistamines with stronger signals represented a very different percentage of the total antihistamine utilization in each Country, e.g. ranging from 43% in Spain (Catalonia) to 97% in Croatia (Fig. 2). Among these, cetirizine was >29 DID in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia (Fig. 3). Drugs with weak signals accounted for no more than 10% (in Sweden) and in most Countries their use was negligible.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus