QT interval prolongation associated with sibutramine treatment

Abstract

Aims To investigate a possible association of sibutramine with QT interval prolongation. Methods Post‐marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database. Results The index case displayed a novel mutation in a cardiac potassium channel subunit gene, KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTc at the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride. Conclusions This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval.

Pharmacotherapy of Childhood Obesity

“…A total of 6.3% of patients became tachycardic, and mean pulse rate increased by 2.5 bpm. No patients developed arrhythmias, but there are reports of ventricular ectopy and prolonged QT syndrome in a few patients treated with sibutramine (47). Sibutramine can also cause insomnia (3.2% of adolescents), dizziness (4%), dry mouth, and constipation and must not be used with monoamine oxidase inhibitors or a variety of other medications that can cause the serotonin syndrome (24).…”

Cardiovascular Risk-Benefit Profile of Sibutramine

“…Further studies are required, but sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval. [89] Another paper reported on a probable association between sibutramine and QT interval prolongation leading to ventricular fibrillation and cardiac arrest in a 51-year-old woman with obesity but no other relevant past medical history or cardiac risk factors. [90] In vitro studies demonstrated that sibutramine preferentially inhibits the hERG potassium channel, in a concentration-dependent manner, an effect that may contribute to prolong the cardiac action potential duration associated with long QT syndrome.…”

Cardiac arrest caused by sibutramine obtained over the Internet: a case of a young woman without pre‐existing cardiovascular disease successfully resuscitated using extracorporeal membrane oxygenation

“…There are two previously published reports of sibutramine‐induced cardiac arrest, but in both cases, sibutramine was prescribed for 1–4 months to treat obesity before the cardiac arrest 4, 5. In the reported cases4, 5 and also the present patient, the QT interval was significantly prolonged at admission and was normalized after discontinuation of sibutramine. The significant impact of this agent on ventricular repolarization, that is, significant increase in QT dispersion, was shown in 65 consecutive patients 6.…”