QT interval prolongation associated with sibutramine treatment

• Published in: British journal of clinical pharmacology Vol. 61; no. 4; pp. 464 - 469
• Main Authors: Harrison‐Woolrych, Mira, Clark, David W. J., Hill, Geraldine R., Rees, Mark I., Skinner, Jonathan R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2006; Blackwell Science
• Subjects: Adult; adverse cardiovascular events; Adverse Drug Reactions; Amino Acid Substitution; Appetite Depressants - adverse effects; Arrhythmias, Cardiac - chemically induced; Arrhythmias, Cardiac - genetics; Arrhythmias, Cardiac - physiopathology; Biological and medical sciences; Cardiac dysrhythmias; Cardiology. Vascular system; congenital long QT syndrome (LQTS); Cyclobutanes - adverse effects; Electrocardiography - methods; Female; Genetic Testing - methods; Heart; Humans; IKs currents; KCNQ1; KCNQ1 Potassium Channel - genetics; Long QT Syndrome - chemically induced; Long QT Syndrome - genetics; Long QT Syndrome - physiopathology; Medical sciences; Mutation; Pharmacology. Drug treatments; Product Surveillance, Postmarketing - methods; QT prolongation; sibutramine; Syncope - chemically induced; Syncope - physiopathology; New Zealand; QT interval; Serotonin; Arrhythmia; Congenital; Toxicity; Prolonged QT interval; Cardiovascular disease; IKs currents; Sibutramine; Catecholamine; Reuptake inhibitor; Conduction disorder; congenital long QT syndrome (LQTS); Treatment; QT prolongation; adverse cardiovascular events; Heart block; Heart disease; KCNQ1; Neurotransmitter; Secondary effect; Norepinephrine; Anorectic
• DOI: 10.1111/j.1365-2125.2006.02574.x
• ISSN: 0306-5251

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.