Non-sedating antihistamine drugs and cardiac arrhythmias -- biased risk estimates from spontaneous reporting systems?
OBJECTIVE
This study used spontaneous reports of adverse events to estimate the risk for developing cardiac arrhythmias due to the systemic use of non-sedating antihistamine drugs and compared the risk estimate before and after the regulatory action to recall the over-the-counter status of some of these drugs.


METHODS
All suspected adverse drug reactions (ADRs) reported until July 1999 to the Netherlands Pharmacovigilance Foundation Lareb were used to calculate the ADR reporting odds ratio, defined as the ratio of exposure odds among reported arrhythmia cases, to the exposure odds of other ADRs (non-cases), adjusted for gender, age, reporter, year of reporting and comedication, stratified for the periods before and after the governmental decision in the Netherlands.


RESULTS
Seven-hundred and thirty-seven cases of arrhythmia were reported, out of which there were 43 instances where the patients were using non-sedating antihistamines. In general non-sedating antihistamines are associated with cardiac arrhythmia to a higher extent in comparison with other drugs (ADR reporting odds ratio 2.05 [95% CI: 1.45, 2.89]). The association between arrhythmias and non-sedating antihistamine drugs calculated before 1998 was not significantly higher than 1 (OR 1.37 [95% CI: 0.85, 2.23]), whereas the risk estimate calculated after the governmental decision did significantly differ from 1 (OR 4.19 [95% CI: 2.49, 7.05]).


CONCLUSIONS
Our data suggest that non-sedating antihistamines might have an increased risk for inducing arrhythmias. Our findings, however, strongly suggest that the increased risk identified can at least partly be explained by reporting bias as a result of publications about and mass media attention for antihistamine induced arrhythmias.
De Bruin
M L
ML
Utrecht Institute for Pharmaceutical Sciences, Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht, The Netherlands. m.l.debruin@pharm.uu.nl
van Puijenbroek
E P
EP
Egberts
A C G
AC
Hoes
A W
AW
Leufkens
H G M
HG
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D015982:Bias; D005260:Female; D006634:Histamine H1 Antagonists / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment
D006634:Histamine H1 Antagonists