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QT interval prolongation associated with sibutramine treatment

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...

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Published in:British journal of clinical pharmacology 2006-04, Vol.61 (4), p.464-469
Main Authors: Harrison‐Woolrych, Mira, Clark, David W. J., Hill, Geraldine R., Rees, Mark I., Skinner, Jonathan R.
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container_start_page 464
container_title British journal of clinical pharmacology
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creator Harrison‐Woolrych, Mira
Clark, David W. J.
Hill, Geraldine R.
Rees, Mark I.
Skinner, Jonathan R.
description 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.
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J. ; Hill, Geraldine R. ; Rees, Mark I. ; Skinner, Jonathan R.</creator><creatorcontrib>Harrison‐Woolrych, Mira ; Clark, David W. J. ; Hill, Geraldine R. ; Rees, Mark I. ; Skinner, Jonathan R.</creatorcontrib><description>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.</description><identifier>ISSN: 0306-5251</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1111/j.1365-2125.2006.02574.x</identifier><identifier>PMID: 16542208</identifier><identifier>CODEN: BCPHBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>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</subject><ispartof>British journal of clinical pharmacology, 2006-04, Vol.61 (4), p.464-469</ispartof><rights>2006 INIST-CNRS</rights><rights>2006 Blackwell Publishing Ltd 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5334-568da8b7939f83451466bd0d5d7cab23a7f2e09039309d259a7308149aaf11ab3</citedby><cites>FETCH-LOGICAL-c5334-568da8b7939f83451466bd0d5d7cab23a7f2e09039309d259a7308149aaf11ab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=17599124$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16542208$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harrison‐Woolrych, Mira</creatorcontrib><creatorcontrib>Clark, David W. J.</creatorcontrib><creatorcontrib>Hill, Geraldine R.</creatorcontrib><creatorcontrib>Rees, Mark I.</creatorcontrib><creatorcontrib>Skinner, Jonathan R.</creatorcontrib><title>QT interval prolongation associated with sibutramine treatment</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>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.</description><subject>Adult</subject><subject>adverse cardiovascular events</subject><subject>Adverse Drug Reactions</subject><subject>Amino Acid Substitution</subject><subject>Appetite Depressants - adverse effects</subject><subject>Arrhythmias, Cardiac - chemically induced</subject><subject>Arrhythmias, Cardiac - genetics</subject><subject>Arrhythmias, Cardiac - physiopathology</subject><subject>Biological and medical sciences</subject><subject>Cardiac dysrhythmias</subject><subject>Cardiology. Vascular system</subject><subject>congenital long QT syndrome (LQTS)</subject><subject>Cyclobutanes - adverse effects</subject><subject>Electrocardiography - methods</subject><subject>Female</subject><subject>Genetic Testing - methods</subject><subject>Heart</subject><subject>Humans</subject><subject>IKs currents</subject><subject>KCNQ1</subject><subject>KCNQ1 Potassium Channel - genetics</subject><subject>Long QT Syndrome - chemically induced</subject><subject>Long QT Syndrome - genetics</subject><subject>Long QT Syndrome - physiopathology</subject><subject>Medical sciences</subject><subject>Mutation</subject><subject>Pharmacology. Drug treatments</subject><subject>Product Surveillance, Postmarketing - methods</subject><subject>QT prolongation</subject><subject>sibutramine</subject><subject>Syncope - chemically induced</subject><subject>Syncope - physiopathology</subject><issn>0306-5251</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqNkE1P3DAQhq2KqiyUv1Dl0t4SPHac2IeuVFblQ1qpVIKzNUkc8CqJt7YXdv99E3YF7Q0fbEvzzDujh5AEaAbjOV9lwAuRMmAiY5QWGWWizLPtBzJ7LRyRGeW0SAUTcExOQlhRChwK8Ykcj3fOGJUzMv99l9ghGv-EXbL2rnPDA0brhgRDcLXFaJrk2cbHJNhqEz32djBJ9AZjb4b4mXxssQvm7PCekvvLn3eL63T56-pm8WOZ1oLzPBWFbFBWpeKqlTwXkBdF1dBGNGWNFeNYtsxQRbniVDVMKCw5lZArxBYAK35K5vvc9abqTVOPoz12eu1tj36nHVr9f2Wwj_rBPWmQUlAuxoBvhwDv_mxMiLq3oTZdh4Nxm6ChBMkB-AjKPVh7F4I37esQoHqSr1d6cqwnx3qSr1_k6-3Y-uXfJd8aD7ZH4OsBwFBj13ocahveuFIoBSwfue977tl2ZvfuBfTF4nb68b8k_KCd</recordid><startdate>200604</startdate><enddate>200604</enddate><creator>Harrison‐Woolrych, Mira</creator><creator>Clark, David W. J.</creator><creator>Hill, Geraldine R.</creator><creator>Rees, Mark I.</creator><creator>Skinner, Jonathan R.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>200604</creationdate><title>QT interval prolongation associated with sibutramine treatment</title><author>Harrison‐Woolrych, Mira ; Clark, David W. J. ; Hill, Geraldine R. ; Rees, Mark I. ; Skinner, Jonathan R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5334-568da8b7939f83451466bd0d5d7cab23a7f2e09039309d259a7308149aaf11ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adult</topic><topic>adverse cardiovascular events</topic><topic>Adverse Drug Reactions</topic><topic>Amino Acid Substitution</topic><topic>Appetite Depressants - adverse effects</topic><topic>Arrhythmias, Cardiac - chemically induced</topic><topic>Arrhythmias, Cardiac - genetics</topic><topic>Arrhythmias, Cardiac - physiopathology</topic><topic>Biological and medical sciences</topic><topic>Cardiac dysrhythmias</topic><topic>Cardiology. Vascular system</topic><topic>congenital long QT syndrome (LQTS)</topic><topic>Cyclobutanes - adverse effects</topic><topic>Electrocardiography - methods</topic><topic>Female</topic><topic>Genetic Testing - methods</topic><topic>Heart</topic><topic>Humans</topic><topic>IKs currents</topic><topic>KCNQ1</topic><topic>KCNQ1 Potassium Channel - genetics</topic><topic>Long QT Syndrome - chemically induced</topic><topic>Long QT Syndrome - genetics</topic><topic>Long QT Syndrome - physiopathology</topic><topic>Medical sciences</topic><topic>Mutation</topic><topic>Pharmacology. Drug treatments</topic><topic>Product Surveillance, Postmarketing - methods</topic><topic>QT prolongation</topic><topic>sibutramine</topic><topic>Syncope - chemically induced</topic><topic>Syncope - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harrison‐Woolrych, Mira</creatorcontrib><creatorcontrib>Clark, David W. J.</creatorcontrib><creatorcontrib>Hill, Geraldine R.</creatorcontrib><creatorcontrib>Rees, Mark I.</creatorcontrib><creatorcontrib>Skinner, Jonathan R.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harrison‐Woolrych, Mira</au><au>Clark, David W. J.</au><au>Hill, Geraldine R.</au><au>Rees, Mark I.</au><au>Skinner, Jonathan R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>QT interval prolongation associated with sibutramine treatment</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>2006-04</date><risdate>2006</risdate><volume>61</volume><issue>4</issue><spage>464</spage><epage>469</epage><pages>464-469</pages><issn>0306-5251</issn><eissn>1365-2125</eissn><coden>BCPHBM</coden><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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>16542208</pmid><doi>10.1111/j.1365-2125.2006.02574.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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source Wiley-Blackwell Read & Publish Collection
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
title QT interval prolongation associated with sibutramine treatment
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