107 lines
38 KiB
Text
107 lines
38 KiB
Text
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
|
|
<head>
|
|
<!-- For pinger, set start time and add meta elements. -->
|
|
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
|
|
|
<!-- Logger begin -->
|
|
<meta name="ncbi_db" content="books">
|
|
<meta name="ncbi_pdid" content="book-part">
|
|
<meta name="ncbi_acc" content="NBK548635">
|
|
<meta name="ncbi_domain" content="livertox">
|
|
<meta name="ncbi_report" content="reader">
|
|
<meta name="ncbi_type" content="fulltext">
|
|
<meta name="ncbi_objectid" content="">
|
|
<meta name="ncbi_pcid" content="/NBK548635/?report=reader">
|
|
<meta name="ncbi_pagename" content="Dofetilide - LiverTox - NCBI Bookshelf">
|
|
<meta name="ncbi_bookparttype" content="chapter">
|
|
<meta name="ncbi_app" content="bookshelf">
|
|
<!-- Logger end -->
|
|
|
|
<!--component id="Page" label="meta"/-->
|
|
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Dofetilide - LiverTox - NCBI Bookshelf</title>
|
|
<meta charset="utf-8">
|
|
<meta name="apple-mobile-web-app-capable" content="no">
|
|
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
|
|
<meta name="jr-col-layout" content="auto">
|
|
<meta name="jr-prev-unit" content="/books/n/livertox/Docusate/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/livertox/Dolutegravir/?report=reader">
|
|
<meta name="bk-toc-url" content="/books/n/livertox/?report=toc">
|
|
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE">
|
|
<meta name="citation_inbook_title" content="LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]">
|
|
<meta name="citation_title" content="Dofetilide">
|
|
<meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases">
|
|
<meta name="citation_date" content="2016/09/15">
|
|
<meta name="citation_pmid" content="31643947">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK548635/">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="Dofetilide">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases">
|
|
<meta name="DC.Date" content="2016/09/15">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK548635/">
|
|
<meta name="description" content="Dofetilide is an oral class III antiarrhythmic agent used for treatment and prevention of atrial fibrillation and flutter. Dofetilide has had limited clinical use, but has not been linked to an increased rate of serum enzyme elevations during therapy or to instances of clinically apparent liver injury.">
|
|
<meta name="og:title" content="Dofetilide">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="Dofetilide is an oral class III antiarrhythmic agent used for treatment and prevention of atrial fibrillation and flutter. Dofetilide has had limited clinical use, but has not been linked to an increased rate of serum enzyme elevations during therapy or to instances of clinically apparent liver injury.">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK548635/">
|
|
<meta name="og:site_name" content="NCBI Bookshelf">
|
|
<meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-livertox-lrg.png">
|
|
<meta name="twitter:card" content="summary">
|
|
<meta name="twitter:site" content="@ncbibooks">
|
|
<meta name="bk-non-canon-loc" content="/books/n/livertox/Dofetilide/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK548635/">
|
|
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&subset=latin" rel="stylesheet" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
|
|
<meta name="format-detection" content="telephone=no">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css//books_print.min.css" type="text/css" media="print">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
|
|
<style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style>
|
|
|
|
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
|
|
<meta name="ncbi_phid" content="CE8B6B097D7C73A10000000000B4009C.m_5">
|
|
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
|
|
<body>
|
|
<!-- Book content! -->
|
|
|
|
|
|
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK548635/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
|
|
<style type="text/css">.st0{fill:#939598;}</style>
|
|
<g>
|
|
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
|
|
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
|
|
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
|
|
</g>
|
|
</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"><a href="/books/n/livertox/Docusate/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="body"><div class="t">Dofetilide</div><div class="j">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]</div></div><div class="tail"><a href="/books/n/livertox/Dolutegravir/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-rtoc-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK548635/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK548635/&text=Dofetilide"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-rtoc-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Table of Content</div></div><div class="cnt lol f1"><a href="/books/n/livertox/?report=reader">Title Information</a><a href="/books/n/livertox/toc/?report=reader">Table of Contents Page</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK548635/?report=classic">Switch to classic view</a><a href="/books/NBK548635/pdf/Bookshelf_NBK548635.pdf">PDF (108K)</a><a href="/books/NBK548635/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK548635%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8B6B097D7C73A10000000000B4009C.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">✘</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK548635_"><span class="title" itemprop="name">Dofetilide</span></h1><p class="fm-aai"><a href="#_NBK548635_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="Dofetilide.OVERVIEW"><h2 id="_Dofetilide_OVERVIEW_">OVERVIEW</h2><div id="Dofetilide.Introduction"><h3>Introduction</h3><p>Dofetilide is an oral class III antiarrhythmic agent used for treatment and prevention of atrial fibrillation and flutter. Dofetilide has had limited clinical use, but has not been linked to an increased rate of serum enzyme elevations during therapy or to instances of clinically apparent liver injury.</p></div><div id="Dofetilide.Background"><h3>Background</h3><p>Dofetilide (doe fet' i lide) is a methanesulfonamide antiarrhythmic agent that is used to treat and prevent recurrence of atrial fibrillation and flutter. Dofetilide is considered a class III antiarrhythmic as it appears to act on a delayed rectifier of a specific potassium channel which results in prolongation of the recovery phase and delay in spread of the action potential. Dofetilide has been shown to lead to spontaneous conversion to normal sinus rhythm in up to 30% of patients with atrial fibrillation, compared to 1% of patients on placebo. Chronic therapy with dofetilide also increased the rate of maintenance of normal sinus rhythm after electro-cardioversion. Dofetilide was approved for use in the United States for atrial fibrillation and flutter in 1999, but its use is restricted and requires physician training in its use as well as initiation of therapy with 3 days of cardiac monitoring and assessment of renal function. Dofetilide is available in capsules of 125, 250 and 500 µg under the brand name Tikosyn. The recommended dose is 500 µg twice daily with dose modification based upon creatinine clearance. Common side effects include headache, dizziness, chest pain and nausea. Uncommon, but potentially severe adverse events include prolongation of the QTc interval (in up to 26%), torsades de pointes (a polymorphic form of ventricular tachycardia), ventricular fibrillation and sudden cardiac death. The frequency of these proarrhythmic side effects is largely dose related.</p></div><div id="Dofetilide.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>In clinical trials, serum aminotransferase and alkaline phosphatase elevations were no more common during dofetilide than placebo therapy. Some degree of ALT elevation was reported in 15% of dofetilide but a similar proportion of placebo recipients; these elevations were above 3 times the upper limit of normal in 1.5% vs 2.0%. Thus, the background rate of serum ALT elevations in patients with atrial fibrillation eligible for dofetilide treatment appears to be high. Despite this, dofetilide has not been linked to instances of clinically apparent liver injury with symptoms or jaundice. The product label for dofetilide does not mention hepatotoxicity and does not specifically recommend monitoring of liver tests.</p><p>Likelihood score: E (unlikely cause of clinically apparent liver injury).</p></div><div id="Dofetilide.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>The mechanism by which dofetilide might cause liver injury is unknown. Dofetilide has a sulfonamide-like structure, but has not been linked to a high rate of hypersensitivity ("sulfa") reactions. The absence of hepatic side effects may be attributable to the low doses used (1 mg or less daily). Dofetilide is metabolized in the liver predominantly by CYP 3A4 and it is susceptible to multiple drug-drug interactions. Dofetilide should not be used in combination with drugs that inhibit CYP 3A4 activity which can cause increases in drug levels and risks of serious ventricular arrhythmias.</p></div><div id="Dofetilide.Outcome_and_Management"><h3>Outcome and Management</h3><p>There is little evidence that dofetilide can cause liver injury, but it has a narrow therapeutic-toxic ratio in relation to cardiac arrhythmias, prolongation of the QTc interval and risk for torsades de pointes. There is little information about cross sensitivity to liver injury between other oral antiarrhythmics and dofetilide.</p><p>Drug Class: <a href="/books/n/livertox/AntiarrhythmicAgents/?report=reader">Antiarrhythmic Agents</a></p></div></div><div id="Dofetilide.PRODUCT_INFORMATION"><h2 id="_Dofetilide_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><div id="Dofetilide.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
|
|
<b>REPRESENTATIVE TRADE NAMES</b>
|
|
</p><p>Dofetilide – Generic, Tikosyn®</p><p>
|
|
<b>DRUG CLASS</b>
|
|
</p><p>Antiarrhythmic Agents</p><p>
|
|
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Dofetilide" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
|
|
</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></div><div id="Dofetilide.CHEMICAL_FORMULA_AND_STRUCTUR"><h2 id="_Dofetilide_CHEMICAL_FORMULA_AND_STRUCTUR_">CHEMICAL FORMULA AND STRUCTURE</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figDofetilideT1"><a href="/books/NBK548635/table/Dofetilide.T1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figDofetilideT1" rid-ob="figobDofetilideT1"><img class="small-thumb" src="/books/NBK548635/table/Dofetilide.T1/?report=thumb" src-large="/books/NBK548635/table/Dofetilide.T1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="Dofetilide.T1"><a href="/books/NBK548635/table/Dofetilide.T1/?report=objectonly" target="object" rid-ob="figobDofetilideT1">Table</a></h4></div></div></div><div id="Dofetilide.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Dofetilide_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 15 September 2016</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Dofetilide.R1">Zimmerman HJ. Antiarrhythmics. Drugs used in cardiovascular disease. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 642-4.<div><i> (Expert review of hepatotoxicity of antiarrhythmics published in 1999 before the availability of dofetilide).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R2">De Marzio DH, Navarro VJ. Hepatotoxicity of cardiovascular and antidiabetic drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 519-40.<div><i> (Review of hepatotoxicity of cardiovascular agents; does not discuss dofetilide).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R3">Sampson KJ, Kass RS. Antiarrhythmic drugs. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 815-48.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R4">Torp-Pedersen C, Møller M, Bloch-Thomsen PE, Køber L, Sandøe E, Egstrup K, Agner E, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. N Engl J Med 1999; 341: 857-65. [<a href="https://pubmed.ncbi.nlm.nih.gov/10486417" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10486417</span></a>]<div><i>(Among 1518 patients with congestive heart failure and left ventricular dysfunction treated with dofetilide or placebo for an average of 18 months, treatment was associated with a higher rate of conversion to normal sinus rhythm [12% vs 1%] and a decrease in need for re-hospitalization, but no difference in mortality; adverse event rates were similar in the 2 groups; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R5">Roden DM. Antiarrhythmic drugs: from mechanisms to clinical practice. Heart 2000; 84: 339-46. [<a href="/pmc/articles/PMC1760959/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1760959</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/10956304" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10956304</span></a>]<div><i>(Overview of antiarrhythmic drugs which are separated into four classes based upon molecular target: I being sodium channel blockers; II beta blockers; III potassium channel blockers; and, IV calcium channel blockers; some agents having multiple targets).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R6">Singh S, Zoble RG, Yellen L, Brodsky MA, Feld GK, Berk M, Billing CB Jr. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. Circulation 2000; 102: 2385-90. [<a href="https://pubmed.ncbi.nlm.nih.gov/11067793" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11067793</span></a>]<div><i>(Among 325 patients with atrial fibrillation-flutter treated with dofetilide [25, 250 or 500 µg] vs placebo twice daily, normal sinus rhythm conversion was more frequent with dofetilide [6-30%] than placebo [1%] and was more frequently maintained [37-58% vs 25%], but torsade de pointes occurred only with dofetilide [n=2; 0.8%] as did sudden cardiac death [n=1]; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R7">Grines CL. Safety and effectiveness of dofetilide for conversion of atrial fibrillation and nesiritide for acute decompensation of heart failure: a report from the cardiovascular and renal advisory panel of the Food and Drug Administration. Circulation. 2000; 101: E200-1. [<a href="https://pubmed.ncbi.nlm.nih.gov/10831533" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10831533</span></a>]<div><i>(Review of the safety and efficacy of dofetilide for atrial fibrillation by the FDA; mentions its narrow therapeutic window, need to adjust dose based upon creatinine clearance and multiple potential drug-drug interactions; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R8">Boriani G, Lubinski A, Capucci A, Niederle R, Kornacewicz-Jack Z, Wnuk-Wojnar AM, Borggrefe M, et al.; Ventricular Arrhythmias Dofetilide Investigators. A multicentre, double-blind randomized crossover comparative study on the efficacy and safety of dofetilide vs sotalol in patients with inducible sustained ventricular tachycardia and ischaemic heart disease. Eur Heart J 2001; 22: 2180-91. [<a href="https://pubmed.ncbi.nlm.nih.gov/11913480" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11913480</span></a>]<div><i>(Among 135 Italian patients with ischemic heart disease at risk of arrhythmias who were treated with dofetilide [500 µg] or sotalol [160 mg] twice daily, overall rates of adverse events were similar in the two groups; no mention of ALT elevations, hypersensitivity reactions or withdrawals for liver related events).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R9">Møller M, Torp-Pedersen CT, Køber L. Dofetilide in patients with congestive heart failure and left ventricular dysfunction: safety aspects and effect on atrial fibrillation. The Danish Investigators of Arrhythmia and Mortality on Dofetilide (DIAMOND) Study Group. Congest Heart Fail 2001; 7 (3): 146-50. [<a href="https://pubmed.ncbi.nlm.nih.gov/11828153" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11828153</span></a>]<div><i>(In a further analysis of the Danish controlled trial of dofetilide vs placebo in 1518 patients with congestive heart failure [Torp-Pederson 1999], the overall adverse event and mortality rates were similar in the 2 groups, but 25 cases of torsade de pointes ventricular tachycardia occurred with dofetilide [2 deaths] but none with placebo; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R10">McNamara RL, Tamariz LJ, Segal JB, Bass EB. Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography. Ann Intern Med 2003; 139: 1018-33. [<a href="https://pubmed.ncbi.nlm.nih.gov/14678922" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14678922</span></a>]<div><i>(Systematic review of literature on drugs for atrial fibrillation; mentions that the major safety concern is the potential to induce polymorphic ventricular tachycardia [torsades de pointes], which usually occurs during the first 3 days of treatment and is most common with quinidine and dofetilide [up to 12%]).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R11">Guanzon AV, Crouch MA. Phase IV trial evaluating the effectiveness and safety of dofetilide. Ann Pharmacother 2004; 38: 1142-7. [<a href="https://pubmed.ncbi.nlm.nih.gov/15161945" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15161945</span></a>]<div><i>(Among 107 patients with atrial fibrillation or flutter treated with dofetilide in clinical practice, none developed torsades de pointes although 26% had excessive QTc prolongation, and rates of conversion to and maintenance of normal sinus rhythm were similar or higher than reported in registration trials; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R12">Drugs for cardiac arrhythmias. Treat Guidel Med Lett 2007; 5: 51-8. [<a href="https://pubmed.ncbi.nlm.nih.gov/17505408" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17505408</span></a>]<div><i>(Concise review of drugs for arrhythmias; dofetilide is used orally to convert atrial fibrillation and maintain sinus rhythm after cardioversion, but is available only through a restricted distribution program requiring that it be started in the hospital with cardiac monitoring).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R13">Camm J. Antiarrhythmic drugs for the maintenance of sinus rhythm: risks and benefits. Int J Cardiol 2012; 155: 362-71. [<a href="https://pubmed.ncbi.nlm.nih.gov/21708411" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21708411</span></a>]<div><i>(Review of the clinical efficacy and safety of drug therapy for maintenance of sinus rhythm after conversion from atrial fibrillation; mentions the proarrhythmic adverse effects of dofetilide and the frequency of torsades de pointes [0.3-4.7%]).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R14">Treatment of atrial fibrillation. Med Lett Drugs Ther 2014; 56 (1446): 53-8. [<a href="https://pubmed.ncbi.nlm.nih.gov/25046325" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25046325</span></a>]<div><i>(Review of drug therapy of atrial fibrillation; mentions that dofetilide is used for rhythm control, particularly in patients with left ventricular dysfunction, but requires in-hospital dose titration and can cause torsades de pointes).</i></div></div></li><li><div class="bk_ref" id="Dofetilide.R15">Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [<a href="/pmc/articles/PMC4446235/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4446235</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25754159" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25754159</span></a>]<div><i>(Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 7 were attributed to antiarrhythmics including 5 to amiodarone, 2 to dronedarone, but none to dofetilide).</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK548635_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">September 15, 2016</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="https://www.niddk.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Institute of Diabetes and Digestive and Kidney Diseases</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Dofetilide. [Updated 2016 Sep 15].<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/livertox/Docusate/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/livertox/Dolutegravir/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="boxed-text" id="figobDofetilideBPI"><div id="Dofetilide.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
|
|
<b>REPRESENTATIVE TRADE NAMES</b>
|
|
</p><p>Dofetilide – Generic, Tikosyn®</p><p>
|
|
<b>DRUG CLASS</b>
|
|
</p><p>Antiarrhythmic Agents</p><p>
|
|
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Dofetilide" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
|
|
</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></article><article data-type="table-wrap" id="figobDofetilideT1"><div id="Dofetilide.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548635/table/Dofetilide.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Dofetilide.T1_lrgtbl__"><table><thead><tr><th id="hd_h_Dofetilide.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">DRUG</th><th id="hd_h_Dofetilide.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">CAS REGISTRY NO.</th><th id="hd_h_Dofetilide.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Dofetilide.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_Dofetilide.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Dofetilide</td><td headers="hd_h_Dofetilide.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/135028787" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">115256-11-6</a>
|
|
</td><td headers="hd_h_Dofetilide.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">C19-H27-N3-O5-S2</td><td headers="hd_h_Dofetilide.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK548635/bin/Dofetilide_Structure.jpg" alt="Dofetilide Chemical Structure" /></div>
|
|
</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
|
|
|
|
|
|
|
|
|
|
<!-- Book content -->
|
|
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
|
|
|
|
|
|
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal104 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
|
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
|
|
|
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3968615.js" snapshot="books"></script></body>
|
|
</html>
|