Citation

Moore N. Therapie 1999; 54(2): e286.

Copyright

(Copyright © 1999, John Libbey Eurotext)

DOI

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PMID

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Abstract

Sertindole has been suspended from the market because of suspected excess risk of cardiovascular mortality, presumably related to QT prolongation, as with other neuroleptics. Though no excess risk was found from clinical trials, post marketing experience could be different. We therefore obtained descriptions of all post-marketing deaths with serttndole, reanalyzed their causality, computed reporting rates in relation to market exposure. In addition, we obtained data from the UK Medicines Control Agency concerning reports of deaths and other adverse reactions with sertindole and other neuroleptics or drags known to cause QT prolongation. There have been 34 deaths reported during sertindole use from beginning of marketing to November 1998. Of these, 14 were non-cardiac (e.g. suicide, pulmonary emboliis. etc.). Of the 20 cardiac or unexpected deaths, there were indications of an organic cause (mainly cardiac ischemia or myocardial infarction) in 16. One patient died suddenly with a prolonged QTc interval, when the drug should have been stopped but was not. [n another case there was no other obvious cause, in two more investigations were still pending. Post-treatment QT data was present in 80% of all cardiac deaths. Overall reported death rate was 0.6 per 100 patient years (PY), of cardiac deaths 0.3 per 100 PY. In a retrospective analysis of 1000 patients on sertindole in Belgium, 2/3 deaths had been reported. In comparison, olanzapine and risperidone had reported death rates of 0.057 per 100 patient years. A PEM study showed that the actual death rate during risperidone treatment was 5.7 per 100 PY. Compared to drugs known to be associated with torsade de pointe, there was a lack of reports of torsade de pointe or palpitations. This analysis showed that the frequency of all and cardiac deaths was not different from that during clinical trials. There is no indication that torsade de pointe is a significant clinical risk with sertindole. The difference with other atypical neuroleptics seems to be due to differential under-reporting.

Language: en