121 lines
40 KiB
Text
121 lines
40 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="NBK547950">
|
|
<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="/NBK547950/?report=reader">
|
|
<meta name="ncbi_pagename" content="Apalutamide - 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>Apalutamide - 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/AntiviralAgents/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/livertox/Apixaban/?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="Apalutamide">
|
|
<meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases">
|
|
<meta name="citation_date" content="2023/03/15">
|
|
<meta name="citation_pmid" content="31643283">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK547950/">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="Apalutamide">
|
|
<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="2023/03/15">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK547950/">
|
|
<meta name="description" content="Apalutamide is a third generation, oral nonsteroidal antiandrogen used to treat nonmetastatic castration-resistant prostate cancer. Apalutamide is associated with a low rate of serum enzyme elevation during therapy but has not been linked to cases of clinically apparent liver injury with jaundice.">
|
|
<meta name="og:title" content="Apalutamide">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="Apalutamide is a third generation, oral nonsteroidal antiandrogen used to treat nonmetastatic castration-resistant prostate cancer. Apalutamide is associated with a low rate of serum enzyme elevation during therapy but has not been linked to cases of clinically apparent liver injury with jaundice.">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK547950/">
|
|
<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/Apalutamide/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK547950/">
|
|
<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="CE8EF2E27D7B4E310000000000F500D1.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/NBK547950/?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/AntiviralAgents/?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">Apalutamide</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/Apixaban/?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/NBK547950/"><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/NBK547950/&text=Apalutamide"><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/NBK547950/?report=classic">Switch to classic view</a><a href="/books/NBK547950/pdf/Bookshelf_NBK547950.pdf">PDF (98K)</a><a href="/books/NBK547950/?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%20NBK547950%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8EF2E27D7B4E310000000000F500D1.4">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="_NBK547950_"><span class="title" itemprop="name">Apalutamide</span></h1><p class="fm-aai"><a href="#_NBK547950_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="Apalutamide.OVERVIEW"><h2 id="_Apalutamide_OVERVIEW_">OVERVIEW</h2><div id="Apalutamide.Introduction"><h3>Introduction</h3><p>Apalutamide is a third generation, oral nonsteroidal antiandrogen used to treat nonmetastatic castration-resistant prostate cancer. Apalutamide is associated with a low rate of serum enzyme elevation during therapy but has not been linked to cases of clinically apparent liver injury with jaundice.</p></div><div id="Apalutamide.Background"><h3>Background</h3><p>Apalutamide (a pa lut' a mide) is a small molecule androgen receptor antagonist which binds to the intracellular receptor and prevents its translocation to the nucleus and subsequent DNA binding, thereby blocking its activity. Therapy with apalutamide lowers residual testosterone levels after surgical castration in men with prostate cancer and has been shown to prolong metastasis free survival in men with castration-resistant prostate cancer with rising levels of prostate-associated antigen (PSA) without measurable metastatic disease. Apalutamide was approved for use in the United States in 2018 and current indications include metastatic, castration-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer. Apalutamide is available as tablets of 60 and 240 mg under brand name Erleada. The recommended initial dose is 240 mg daily with subsequent dose reduction for intolerance. It should be administered with a gonadotropin-releasing hormone (GnRH) analog or after bilateral orchiectomy to insure optimal androgen suppression. Common side effects include symptoms of androgen deficiency including fatigue, diarrhea, nausea, anorexia, weight loss, constipation, joint and muscle pain, hot flushes, headaches, dizziness, and edema. Rare, but potentially serious side effects associated with long term therapy include seizures, osteoporosis, falls, bone fractures, severe cutaneous adverse events, embryo-fetal toxicity, and cardiovascular events.</p></div><div id="Apalutamide.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>In prelicensure controlled trials of apalutamide, serum aminotransferase elevations were uncommon and generally transient and mild, not requiring dose modification. Clinically apparent liver injury with jaundice attributable to apalutamide was not reported in the preregistration trials and is not mentioned as an adverse event in the product label. Since the approval and general clinical use of apalutamide, there have been no publications or descriptions of the clinical features of hepatotoxicity with jaundice associated with its use. The first and second generation androgen receptor blockers, flutamide, nilutamide, and bicalutamide, have all been linked to instances of hepatitis-like liver injury with jaundice that can be severe and even fatal. However, such cases have not been described with apalutamide and other third generation androgen receptor antagonists. Thus, clinically apparent liver injury due to apalutamide must be rare, if it occurs at all.</p><p>Likelihood score: E (unlikely cause of clinically apparent liver injury).</p></div><div id="Apalutamide.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>The possible cause of liver injury due to apalutamide therapy is unknown. While first and second generation antiandrogens have been implicated in causing liver injury, the more potent third general factors have not. Apalutamide is extensively metabolized in the liver predominantly by CYP 2C8 and 3A and is an inducer of CYP 3A4. While coadministration of apalutamide with substrates of CYP 3A4 and with modulators of CYP 2C8 and 3A4 may result in drug-drug interactions, the effects are relatively modest.</p></div><div id="Apalutamide.Outcome_and_Management"><h3>Outcome and Management</h3><p>The liver injury linked to apalutamide therapy has been generally mild, consisting of transient and asymptomatic elevations in serum aminotransferase levels and rarely requiring dose modification or discontinuation. Apalutamide has not been linked to cases of acute liver failure, chronic hepatitis or vanishing bile duct syndrome. There is no information on cross sensitivity to hepatic injury between apalutamide and other antiandrogens, such as flutamide, bicalutamide, or abiraterone.</p><p>Drug Class: <a href="/books/n/livertox/AntineoplasticAgents/?report=reader">Antineoplastic Agents</a>, <a href="/books/n/livertox/Anti-androgens/?report=reader">Antiandrogens</a></p></div></div><div id="Apalutamide.PRODUCT_INFORMATION"><h2 id="_Apalutamide_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><p>
|
|
<b>REPRESENTATIVE TRADE NAMES</b>
|
|
</p><p>Apalutamide – Erleada®</p><p>
|
|
<b>DRUG CLASS</b>
|
|
</p><p>Antineoplastic Agents</p><p>
|
|
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Apalutamide" 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 id="Apalutamide.CHEMICAL_FORMULA_AND_STRUCTU"><h2 id="_Apalutamide_CHEMICAL_FORMULA_AND_STRUCTU_">CHEMICAL FORMULA AND STRUCTURE</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figApalutamideTc"><a href="/books/NBK547950/table/Apalutamide.Tc/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figApalutamideTc" rid-ob="figobApalutamideTc"><img class="small-thumb" src="/books/NBK547950/table/Apalutamide.Tc/?report=thumb" src-large="/books/NBK547950/table/Apalutamide.Tc/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="Apalutamide.Tc"><a href="/books/NBK547950/table/Apalutamide.Tc/?report=objectonly" target="object" rid-ob="figobApalutamideTc">Table</a></h4></div></div></div><div id="Apalutamide.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Apalutamide_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 15 March 2023</p><p>Abbreviations: LHRH, luteinizing hormone releasing hormone, PSA, prostate-specific antigen.</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Apalutamide.REF.zimmerman.1999">Zimmerman HJ. Hepatotoxic effects of oncotherapeutic and immunosuppressive agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 673-708.<div><i>(Expert review of hepatotoxicity of cancer chemotherapeutic agents published in 1999 before the availability of apalutamide).</i></div></div></li><li><div class="bk_ref" id="Apalutamide.REF.deleve.2013">DeLeve LD. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam, Elsevier, 2013, p. 541-68.<div><i>(Review of hepatotoxicity of cancer chemotherapeutic agents; apalutamide is not discussed).</i></div></div></li><li><div class="bk_ref" id="Apalutamide.REF.isaacs.2018">Isaacs C, Wellstein A, Riegel AT. Hormones and related agents in the therapy of cancer. Natural products in cancer chemotherapy: hormones and related agents. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1237-48.<div><i>(Textbook of pharmacology and therapeutics discusses the androgen receptor antagonists flutamide, bicalutamide, nilutamide and enzalutamide, but not apalutamide).</i></div></div></li><li><div class="bk_ref" id="Apalutamide.REF.fda">FDA. <a href="https://www.accessdata.fda.gov/scripts/cder/daf/" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.accessdata<wbr style="display:inline-block"></wbr>​.fda.gov/scripts/cder/daf/</a><div><i>(FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA scientific review of the new drug application for safety and efficacy; mentions that hepatic laboratory abnormalities were uncommon and the single instance of clinically apparent liver injury with jaundice appeared to be due to progressive hepatic metastases rather than apalutamide toxicity).</i></div></div></li><li><div class="bk_ref" id="Apalutamide.REF.tran.2009.787">Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. <span><span class="ref-journal">Science. </span>2009;<span class="ref-vol">324</span>:787–90.</span> [<a href="/pmc/articles/PMC2981508/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2981508</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19359544" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19359544</span></a>]<div>
|
|
<i>(Description of development of unique antiandrogen molecules that block the translocation of the androgen receptor to the nucleus and the transcriptional activity of the receptor).</i>
|
|
</div></div></li><li><div class="bk_ref" id="Apalutamide.REF.smith.2016.963">Smith MR, Antonarakis ES, Ryan CJ, Berry WR, Shore ND, Liu G, Alumkal JJ, et al. Phase 2 study of the safety and antitumor activity of apalutamide (ARN-509), a potent androgen receptor antagonist, in the high-risk nonmetastatic castration-resistant prostate cancer cohort. <span><span class="ref-journal">Eur Urol. </span>2016;<span class="ref-vol">70</span>:963–70.</span> [<a href="/pmc/articles/PMC5568792/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5568792</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27160947" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27160947</span></a>]<div>
|
|
<i>(Among 51 patients with castration-resistant prostate cancer and rising levels of PSA who were treated with apalutamide [240 mg daily], 89% had a 50% decline in PSA levels within 12 weeks and common side effects were fatigue [61%], diarrhea [43%], nausea [39%], joint and back pain [22%], hot flush [20%] and abdominal pain [18%], and no serious adverse events occurred; no mention of ALT elevations or hepatotoxicity).</i>
|
|
</div></div></li><li><div class="bk_ref" id="Apalutamide.REF.rathkopf.2017.3544">Rathkopf DE, Antonarakis ES, Shore ND, Tutrone RF, Alumkal JJ, Ryan CJ, Saleh M, et al. Safety and antitumor activity of apalutamide (ARN-509) in metastatic castration-resistant prostate cancer with and without prior abiraterone acetate and prednisone. <span><span class="ref-journal">Clin Cancer Res. </span>2017;<span class="ref-vol">23</span>:3544–51.</span> [<a href="/pmc/articles/PMC5543693/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5543693</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28213364" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28213364</span></a>]<div>
|
|
<i>(Among 46 men with castration-resistant prostate cancer and rising PSA levels treated with apalutamide [240 mg daily], 88% had at least a 50% decline in PSA levels by 12 weeks, side effects were mostly mild, and there were no treatment-related serious adverse events; no mention of ALT elevations or hepatotoxicity).</i>
|
|
</div></div></li><li><div class="bk_ref" id="Apalutamide.REF.smith.2018.1408">Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, et al. SPARTAN Investigators. Apalutamide treatment and metastasis-free survival in prostate cancer. <span><span class="ref-journal">N Engl J Med. </span>2018;<span class="ref-vol">378</span>:1408–18.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29420164" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29420164</span></a>]<div>
|
|
<i>(Among 1207 men with castration-resistant prostate cancer with rising levels of PSA but without detectable metastases in a randomized, placebo controlled trial, median metastasis-free survival was longer with apalutamide than placebo [40.5 vs 16.2 months], and adverse events that were more frequent with apalutamide included fatigue [30% vs 21%], rash [24% vs 6%], weight loss [16% vs 6%], falls [16% vs 9%], fractures [12% vs 7%], hypothyroidism [8% vs 2%] and seizures [0.2% vs none]; no mention of ALT elevations or hepatotoxicity).</i>
|
|
</div></div></li><li><div class="bk_ref" id="Apalutamide.REF.beaver.2018.2458">Beaver JA, Kluetz PG, Pazdur R. Metastasis-free survival – a new end point in prostate cancer trials. <span><span class="ref-journal">N Engl J Med. </span>2018;<span class="ref-vol">378</span>:2458–60.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29949489" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29949489</span></a>]<div>
|
|
<i>(Editorial from FDA on the implications of the approval of apalutamide and application of metastasis-free survival [rather than overall survival] as an end-point in assessing efficacy of new agents for prostate cancer, stressing the importance of balancing benefit with safety and risk of adverse events).</i>
|
|
</div></div></li><li><div class="bk_ref" id="Apalutamide.REF.alsalama.2018.699">Al-Salama ZT. Apalutamide: first global approval. <span><span class="ref-journal">Drugs. </span>2018;<span class="ref-vol">78</span>:699–705.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29626324" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29626324</span></a>]<div>
|
|
<i>(Review of the structure, mechanism of action, history of development, clinical efficacy and safety of apalutamide; mentions that overall and serious adverse event rates were similar in apalutamide- and placebo-treated subjects; no mention of ALT elevations or hepatotoxicity).</i>
|
|
</div></div></li><li><div class="bk_ref" id="Apalutamide.REF11">Apalutamide (Erleada) for prostate cancer. <span><span class="ref-journal">Med Lett Drugs Ther. </span>2018;<span class="ref-vol">60</span>(1551):e124–e125.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30036351" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30036351</span></a>]<div>
|
|
<i>(Concise review of the efficacy, safety and costs of apalutamide shortly after its approval in the US mentions side effects reported by Smith et al. [2018], but does not mention hepatotoxicity or ALT elevations).</i>
|
|
</div></div></li><li><div class="bk_ref" id="Apalutamide.REF.crawford.2018.956">Crawford ED, Schellhammer PF, McLeod DG, Moul JW, Higano CS, Shore N, Denis L, et al. Androgen receptor targeted treatments of prostate cancer: 35 years of progress with antiandrogens. <span><span class="ref-journal">J Urol. </span>2018;<span class="ref-vol">200</span>:956–966.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29730201" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29730201</span></a>]<div>
|
|
<i>(Review of the development of antiandrogen therapies of prostate cancer starting with discovery of the androgen sensitive nature of prostate cancer, the effects of orchiectomy, followed by the development of androgen receptor antagonists, first generation agents flutamide and nilutamide, second generation agent bicalutamide and third generation agents enzalutamide, apalutamide and darolutamide that have more potent androgen receptor inhibition).</i>
|
|
</div></div></li><li><div class="bk_ref" id="Apalutamide.REF.halabi.2021.298">Halabi S, Jiang S, Terasawa E, Garcia-Horton V, Ayyagari R, Waldeck AR, Shore N. Indirect comparison of darolutamide versus apalutamide and enzalutamide for nonmetastatic castration-resistant prostate cancer. <span><span class="ref-journal">J Urol. </span>2021;<span class="ref-vol">206</span>:298–307.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/33818140" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33818140</span></a>]<div>
|
|
<i>(Comparison of outcome and adverse events in published randomized, placebo-controlled trials of darolutamide, apalutamide and enzalutamide for castration-resistant prostate cancer suggested that efficacy as assessed by improvement in metastasis-free survival was similar for all three agents, but that darolutamide therapy was associated with lower rates of adverse events, particularly fatigue, rash, falls, seizures, fractures and cognitive disorders; no mention of ALT elevations or hepatotoxicity).</i>
|
|
</div></div></li><li><div class="bk_ref" id="Apalutamide.REF.saad.2021.1541">Saad F, Efstathiou E, Attard G, Flaig TW, Franke F, Goodman OB Jr, Oudard S, et al. ACIS Investigators. Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study. <span><span class="ref-journal">Lancet Oncol. </span>2021;<span class="ref-vol">22</span>:1541–1559.</span> [<a href="/pmc/articles/PMC9377412/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9377412</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34600602" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34600602</span></a>]<div>
|
|
<i>(Among 982 men with metastatic prostate cancer treated with abiraterone [1000 mg with prednisone] with or without apalutamide [240 mg], radiographic progression free survival was longer with combination therapy [22.6 vs 16.6 months], but overall survival was not different [67% vs 69%] and adverse events were more frequent with the combination, including hypertension [17% vs 10%] and ALT elevations [12% vs 4%], but there were no hepatic deaths or mention of clinically apparent liver injury).</i>
|
|
</div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK547950_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">March 15, 2023</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-. Apalutamide. [Updated 2023 Mar 15].<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/livertox/AntiviralAgents/?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/Apixaban/?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="table-wrap" id="figobApalutamideTc"><div id="Apalutamide.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK547950/table/Apalutamide.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Apalutamide.Tc_lrgtbl__"><table><thead><tr><th id="hd_h_Apalutamide.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DRUG</th><th id="hd_h_Apalutamide.Tc_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CAS REGISTRY NUMBER</th><th id="hd_h_Apalutamide.Tc_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Apalutamide.Tc_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_Apalutamide.Tc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Apalutamide</td><td headers="hd_h_Apalutamide.Tc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/162108672" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">956104-40-8</a>
|
|
</td><td headers="hd_h_Apalutamide.Tc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">C21-H15-F4-N5-O2-S</td><td headers="hd_h_Apalutamide.Tc_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/162108672" title="View this structure in PubChem" class="img_link" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem"><img src="https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?t=l&sid=162108672" alt="image 162108672 in the ncbi pubchem database" /></a>
|
|
</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 portal107 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>
|