105 lines
39 KiB
Text
105 lines
39 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="NBK548866">
|
|
<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="/NBK548866/?report=reader">
|
|
<meta name="ncbi_pagename" content="Drotrecogin alfa - 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>Drotrecogin alfa - 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/Dronedarone/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/livertox/Droxidopa/?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="Drotrecogin alfa">
|
|
<meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases">
|
|
<meta name="citation_date" content="2018/01/08">
|
|
<meta name="citation_pmid" content="31644173">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK548866/">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="Drotrecogin alfa">
|
|
<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="2018/01/08">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK548866/">
|
|
<meta name="description" content="Drotrecogin alfa is a recombinant form of activated human protein C which was previously used to treat patients with severe sepsis and organ failure. Drotrecogin alfa was typically given to critically ill patients in whom severe adverse events were common, but it was never linked to an increase in significant serum enzyme elevations during therapy or to instances of clinically apparent liver injury.">
|
|
<meta name="og:title" content="Drotrecogin alfa">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="Drotrecogin alfa is a recombinant form of activated human protein C which was previously used to treat patients with severe sepsis and organ failure. Drotrecogin alfa was typically given to critically ill patients in whom severe adverse events were common, but it was never linked to an increase in significant 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/NBK548866/">
|
|
<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/DrotrecoginAlfa/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK548866/">
|
|
<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="CE8B572B7D7C5A410000000000D900C0.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/NBK548866/?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/Dronedarone/?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">Drotrecogin alfa</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/Droxidopa/?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/NBK548866/"><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/NBK548866/&text=Drotrecogin%20alfa"><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/NBK548866/?report=classic">Switch to classic view</a><a href="/books/NBK548866/pdf/Bookshelf_NBK548866.pdf">PDF (93K)</a><a href="/books/NBK548866/?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%20NBK548866%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8B572B7D7C5A410000000000D900C0.4">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="_NBK548866_"><span class="title" itemprop="name">Drotrecogin alfa</span></h1><p class="fm-aai"><a href="#_NBK548866_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="DrotrecoginAlfa.OVERVIEW"><h2 id="_DrotrecoginAlfa_OVERVIEW_">OVERVIEW</h2><div id="DrotrecoginAlfa.Introduction"><h3>Introduction</h3><p>Drotrecogin alfa is a recombinant form of activated human protein C which was previously used to treat patients with severe sepsis and organ failure. Drotrecogin alfa was typically given to critically ill patients in whom severe adverse events were common, but it was never linked to an increase in significant serum enzyme elevations during therapy or to instances of clinically apparent liver injury.</p></div><div id="DrotrecoginAlfa.Background"><h3>Background</h3><p>Drotrecogin (droe" tre koe' jin) alfa is a recombinant form of activated human protein C, which is believed to intervene in multiple sites in the systemic response to infection and to be deficient in some patients with severe septicemia. Protein C is a serine protease that has antithrombotic, antiinflammatory and profibrinolytic properties which may play a role in limiting the injurious effects of the severe systemic response to septicemia. Administration of drotrecogin alfa in patients with severe sepsis and organ failure was initially reported to improve outcomes, decreasing 28 day mortality. However, subsequent large, randomized controlled trials found no evidence for its efficacy in severe sepsis. Drotrecogin alfa was approved in the United States for use in severe sepsis with acute organ failure and high risk of death in 2001. After postmarketing studies demonstrated that it had little or no effect on mortality, it was withdrawn by the sponsor in 2011. Drotrecogin alfa was previously available in single use vials of 5 and 20 mg under the brand name Xigris. The recommended dose was 24 µg/kg per hour for 96 hours. Side effects were difficult to attribute to the therapy because the drug was used only in critically ill patients, in whom severe adverse events were common and expected. Adverse events thought to be due to the drotrecogin alfa infusions included bleeding which could be severe, but was rarely fatal.</p></div><div id="DrotrecoginAlfa.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>In preregistration studies of drotrecogin alfa, no mention was made of serum enzyme elevations or episodes of clinically apparent liver injury. However, patients treated were critically ill and sepsis on its own commonly causes serum enzyme elevations and jaundice. After approval and more widespread use of drotrecogin alfa, there were no published reports of hepatotoxicity associated with its use. The withdrawal of drotrecogin alfa in 2011 was based upon its relative lack of efficacy rather than safety.</p><p>Likelihood score: E (unlikely cause of clinically apparent liver injury).</p></div><div id="DrotrecoginAlfa.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>The mechanism by which drotrecogin alfa might cause serum aminotransferase elevations or liver injury is not known. It is a recombinant glycoprotein with the same amino acid sequence as the human protein and thus unlikely to be intrinsically toxic or immunogenic. Allergic reactions and development of antibodies to human protein C were not reported.</p><p>Drug Class: <a href="/books/n/livertox/Anticoagulants/?report=reader">Antithrombotic Agents</a>, Agents for Sepsis</p></div></div><div id="DrotrecoginAlfa.PRODUCT_INFORMATION"><h2 id="_DrotrecoginAlfa_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><div id="DrotrecoginAlfa.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
|
|
<b>REPRESENTATIVE TRADE NAMES</b>
|
|
</p><p>Drotrecogin alfa – Xigris®</p><p>
|
|
<b>DRUG CLASS</b>
|
|
</p><p>Agents for Sepsis</p><p>
|
|
<b>COMPLETE LABELING</b>
|
|
</p><p>Product Withdrawn from Market</p></div></div><div id="DrotrecoginAlfa.CHEMICAL_FORMULA_AND_STR"><h2 id="_DrotrecoginAlfa_CHEMICAL_FORMULA_AND_STR_">CHEMICAL FORMULA AND STRUCTURE</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figDrotrecoginAlfaT1"><a href="/books/NBK548866/table/DrotrecoginAlfa.T1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figDrotrecoginAlfaT1" rid-ob="figobDrotrecoginAlfaT1"><img class="small-thumb" src="/books/NBK548866/table/DrotrecoginAlfa.T1/?report=thumb" src-large="/books/NBK548866/table/DrotrecoginAlfa.T1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="DrotrecoginAlfa.T1"><a href="/books/NBK548866/table/DrotrecoginAlfa.T1/?report=objectonly" target="object" rid-ob="figobDrotrecoginAlfaT1">Table</a></h4></div></div></div><div id="DrotrecoginAlfa.ANNOTATED_BIBLIOGRAPHY"><h2 id="_DrotrecoginAlfa_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 08 January 2018</p><ul class="first-line-outdent"><li><div class="bk_ref" id="DrotrecoginAlfa.R1">Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, et al.; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699-709. [<a href="https://pubmed.ncbi.nlm.nih.gov/11236773" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11236773</span></a>]<div><i>(Among 1690 patients with severe sepsis with organ failure who were treated with drotrecogin alfa or placebo infusions for 96 hours, 28 day all-cause mortality was lower with drotrecogin than placebo [24.7% vs 30.8%]; important side effects included serious bleeding episodes [3.5% vs 2.0%], but "there were no other safety concerns...on the basis of assessments of organ dysfunction, vital signs, serum chemical data, or hematologic data").</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R2">Bernard GR, Margolis BD, Shanies HM, Ely EW, Wheeler AP, Levy H, Wong K, Wright TJ; Extended Evaluation of Recombinant Human Activated Protein C United States Investigators. Extended evaluation of recombinant human activated protein C United States Trial (ENHANCE US): a single-arm, phase 3B, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest 2004; 125: 2206-16. [<a href="https://pubmed.ncbi.nlm.nih.gov/15189943" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15189943</span></a>]<div><i>(Among 273 adults with severe sepsis with organ failure treated with drotrecogin alfa infusions, the 28 day mortality rate was 26.4% and serious bleeding episodes [the only serious adverse event attributed to drug] occurred in 4%; no mention of serum enzyme elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R3">Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, François B, et al; Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) Study Group. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 2005; 353: 1332-41. [<a href="https://pubmed.ncbi.nlm.nih.gov/16192478" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16192478</span></a>]<div><i>(Among 2613 patients with severe sepsis but a "low risk of death" who were treated with drotrecogin alfa or placebo infusions for 96 hours, 28 day mortality was similar in both groups [18.5% vs 17%] while serious bleeding episodes were more frequent with drotrecogin [2.4% vs 1.2%]; no mention or serum enzyme elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R4">Payen D, Sundin DP, Nelson DR, Williams MD. Analysis of efficacy and safety of drotrecogin alfa (activated) in surgical patients, using an international integrated database. Surgery 2007; 142: 426-7. [<a href="https://pubmed.ncbi.nlm.nih.gov/17723900" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17723900</span></a>]<div><i>(Among 1659 patients with severe sepsis following surgery who participated in 5 clinical studies of drotrecogin alfa vs placebo, serious bleeding episodes were more common with drotrecogin than placebo [4.9% vs 0.5%], but were rarely fatal).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R5">Laterre PF, Abraham E, Janes JM, Trzaskoma BL, Correll NL, Booth FV. ADDRESS (ADministration of DRotrecogin alfa [activated] in Early stage Severe Sepsis) long-term follow-up: one-year safety and efficacy evaluation. Crit Care Med 2007; 35: 1457-63. [<a href="https://pubmed.ncbi.nlm.nih.gov/17452935" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17452935</span></a>]<div><i>(Among 2640 patients who received drotrecogin alfa or placebo infusions for an episode of "early stage" severe sepsis with organ failure [Abraham 2005], one year follow up was available on 2376 at which time mortality rates were similar [34.2% vs 34%]).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R6">Payen D, Sablotzki A, Barie PS, Ramsay G, Lowry S, Williams M, Sarwat S, et al. International integrated database for the evaluation of severe sepsis and drotrecogin alfa (activated) therapy: analysis of efficacy and safety data in a large surgical cohort. Surgery 2007; 141: 548-61. [<a href="https://pubmed.ncbi.nlm.nih.gov/17431957" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17431957</span></a>]<div><i>(Retrospective analysis using a large integrated database on patients with severe sepsis after surgery who received drotrecogin alfa found that serious adverse events were more common with drotrecogin than placebo [7.5% vs 6.3%] as were severe bleeding episodes [4.9% vs 0.5%]; no mention of liver related adverse events).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R7">Nadel S, Goldstein B, Williams MD, Dalton H, Peters M, Macias WL, Abd-Allah SA, et al.; REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective (RESOLVE) study group. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet 2007; 369 (9564): 836-43. [<a href="https://pubmed.ncbi.nlm.nih.gov/17350452" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17350452</span></a>]<div><i>(Among 477 children with severe sepsis and organ failure treated with infusions of drotrecogin alfa vs placebo for 96 hours, 28 day mortality [17.2% vs 17.5%] and rates of severe bleeding [6.7% vs 6.8%] were similar and "the overall safety profile [was] acceptable"; no mention of serum enzyme elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R8">Dhainaut JF; INDEPTH Clinical Evaluation Committee. International integrated database for the evaluation of severe sepsis (INDEPTH): clinical evaluation committee report on the safety of drotrecogin alfa (activated) therapy. Curr Med Res Opin 2008; 24: 1187-97. [<a href="https://pubmed.ncbi.nlm.nih.gov/18348744" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18348744</span></a>]<div><i>(Among 4459 patients with severe sepsis enrolled in studies of drotrecogin alfa vs placebo and analyzed in an integrated database, total serious adverse event rates were similar [13.2% vs 13.8%], while serious bleeding episodes more frequent with drotrecogin than placebo [5.6% vs 2.0%] and arterial thrombotic events less common with drotrecogin [1.8% vs 2.9%]).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R9">Woodward B, Cartwright M. Safety of drotrecogin alfa (activated) in severe sepsis: data from adult clinical trials and observational studies. J Crit Care 2009; 24: 595-602. [<a href="https://pubmed.ncbi.nlm.nih.gov/19327331" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19327331</span></a>]<div><i>(Review of safety analyses of 2 controlled and 4 open label trials of drotrecogin alfa in severe sepsis from the sponsor focuses upon serious bleeding episodes and does not discuss serum enzyme elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R10">Poole D, Bertolini G, Garattini S. Errors in the approval process and post-marketing evaluation of drotrecogin alfa (activated) for the treatment of severe sepsis. Lancet Infect Dis 2009; 9: 67-72. [<a href="https://pubmed.ncbi.nlm.nih.gov/19095197" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19095197</span></a>]<div><i>(Analysis of the approval of drotrecogin alfa in the US and Europe points out that the approval was based upon analysis of subgroups of patients in the initial single trial in patients with severe sepsis and organ failure).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R11">Steingrub JS, Cheatham ML, Woodward B, Wang HT, Effron MB; XEUS Investigators. A prospective, observational study of Xigris Use in the United States (XEUS). J Crit Care 2010; 25: 660. [<a href="https://pubmed.ncbi.nlm.nih.gov/20435433" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20435433</span></a>]<div><i>(Among 548 adults with severe sepsis treated with drotrecogin alfa in clinical practices, 28 day mortality was 36.7% and the rate of serious bleeding episodes 3.1%; no mention of serum enzyme elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R12">Kalil AC, LaRosa SP. Effectiveness and safety of drotrecogin alfa (activated) for severe sepsis: a meta-analysis and metaregression. Lancet Infect Dis 2012; 12: 678-86. [<a href="https://pubmed.ncbi.nlm.nih.gov/22809883" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22809883</span></a>]<div><i>(Systematic review of literature [9 controlled trials and 20 open label studies] on drotrecogin alfa therapy of severe sepsis concludes that drotrecogin treatment was associated with a reduction in hospital mortality).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R13">Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gårdlund B, et al; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012; 366: 2055-64. [<a href="https://pubmed.ncbi.nlm.nih.gov/22616830" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22616830</span></a>]<div><i>(Among 1697 patients with septic shock treated with drotrecogin alfa or placebo infusions for 96 hours, 28 day mortality was similar in both groups [26.4% vs 24.7%], while serious adverse events were more frequent with drotrecogin [14.3% vs 11.5%] as was serious bleeding [8.6% vs 4.8%]; rates of hepatic failure were similar in both groups).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R14">Holder AL, Huang DT. A dream deferred: the rise and fall of recombinant activated protein C. Crit Care 2013; 17: 309. [<a href="/pmc/articles/PMC3672523/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3672523</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23509922" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23509922</span></a>]<div><i>(Commentary on Ranieri [2012] concludes that "drotrecogin should no longer be recommended in sepsis guidelines as a standard of care").</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R15">Annane D, Timsit JF, Megarbane B, Martin C, Misset B, Mourvillier B, Siami S, et al.; APROCCHSS Trial Investigators. Recombinant human activated protein C for adults with septic shock: a randomized controlled trial. Am J Respir Crit Care Med 2013; 187: 1091-7. [<a href="https://pubmed.ncbi.nlm.nih.gov/23525934" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23525934</span></a>]<div><i>(Among 411 patients with septic shock treated with drotrecogin alfa, corticosteroids, both or placebos, 90 day mortality was the same for the regimens with or without drotrecogin [47.6% vs 46.3%] as were the rates of serious adverse events [53.8% vs 54.7%] and serious bleeding [12,5% vs 14.3%]; no mention of serum enzyme elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="DrotrecoginAlfa.R16">Miranda CJ, Mason JM, Babu BI, Sheen AJ, Eddleston JM, Parker MJ, Pemberton P, Siriwardena AK. Twenty-four hour infusion of human recombinant activated protein C (Xigris) early in severe acute pancreatitis: The XIG-AP 1 trial. Pancreatology 2015; 15: 635-41. [<a href="https://pubmed.ncbi.nlm.nih.gov/26547592" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26547592</span></a>]<div><i>(Among 19 patients with severe acute pancreatitis treated with drotrecogin alfa infusions for 24 hours, 28 day mortality was slightly but not significantly higher than that of historical controls [11% vs 5%] and treated patients had no serious bleeding episodes; no mention of serum enzyme elevations or hepatotoxicity).</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK548866_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">January 8, 2018</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-. Drotrecogin alfa. [Updated 2018 Jan 8].<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/livertox/Dronedarone/?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/Droxidopa/?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="figobDrotrecoginAlfaBPI"><div id="DrotrecoginAlfa.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
|
|
<b>REPRESENTATIVE TRADE NAMES</b>
|
|
</p><p>Drotrecogin alfa – Xigris®</p><p>
|
|
<b>DRUG CLASS</b>
|
|
</p><p>Agents for Sepsis</p><p>
|
|
<b>COMPLETE LABELING</b>
|
|
</p><p>Product Withdrawn from Market</p></div></article><article data-type="table-wrap" id="figobDrotrecoginAlfaT1"><div id="DrotrecoginAlfa.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548866/table/DrotrecoginAlfa.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__DrotrecoginAlfa.T1_lrgtbl__"><table><thead><tr><th id="hd_h_DrotrecoginAlfa.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">DRUG</th><th id="hd_h_DrotrecoginAlfa.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">CAS REGISTRY NUMBER</th><th id="hd_h_DrotrecoginAlfa.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_DrotrecoginAlfa.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_DrotrecoginAlfa.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Drotrecogin alfa</td><td headers="hd_h_DrotrecoginAlfa.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/135353175" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">98530-76-8</a>
|
|
</td><td headers="hd_h_DrotrecoginAlfa.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Unspecified</td><td headers="hd_h_DrotrecoginAlfa.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Not Available</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>
|