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<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="Ticagrelor" /><meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases" /><meta name="citation_date" content="2020/09/25" /><meta name="citation_pmid" content="31643847" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK548529/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Ticagrelor" /><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="2020/09/25" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK548529/" /><meta name="description" content="Ticagrelor is an oral antiplatelet drug that is used with low dose aspirin to decrease the risk of myocardial infarction and stroke in patients with acute coronary syndromes. Ticagrelor has been linked to rare instances of hypersensitivity reactions accompanied by mild liver injury." /><meta name="og:title" content="Ticagrelor" /><meta name="og:type" content="book" /><meta name="og:description" content="Ticagrelor is an oral antiplatelet drug that is used with low dose aspirin to decrease the risk of myocardial infarction and stroke in patients with acute coronary syndromes. Ticagrelor has been linked to rare instances of hypersensitivity reactions accompanied by mild liver injury." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK548529/" /><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/Ticagrelor/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK548529/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><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" /><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><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><meta name="book-collection" content="NONE" />
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All Drug Records" href="/books/n/livertox/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-livertox-lrg.png" alt="Cover of LiverTox" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK548529_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK548529_dtls__"><div>Bethesda (MD): <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>; 2012-.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/livertox/">Drug Records</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/livertox/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/livertox/Tibolone/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/livertox/Ticarcillin/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK548529_"><span class="title" itemprop="name">Ticagrelor</span></h1><p class="small">Last Update: <span itemprop="dateModified">September 25, 2020</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="Ticagrelor.OVERVIEW"><h2 id="_Ticagrelor_OVERVIEW_">OVERVIEW</h2><div id="Ticagrelor.Introduction"><h3>Introduction</h3><p>Ticagrelor is an oral antiplatelet drug that is used with low dose aspirin to decrease the risk of myocardial infarction and stroke in patients with acute coronary syndromes. Ticagrelor has been linked to rare instances of hypersensitivity reactions accompanied by mild liver injury.</p></div><div id="Ticagrelor.Background"><h3>Background</h3><p>Ticagrelor (tye ka' grel or) is a non-thienopyridine, reversible inhibitor of adenosine diphosphate (ADP) receptors (P2Y 12) on platelets and is used to decrease the risk of recurrent coronary thromboses in patients who undergo interventions during an acute coronary syndrome. Activated platelets release ADP which binds to ADP platelet receptors, causing activation of intracellular glycoprotein IIb/IIIA complex which triggers platelet adherence and aggregation. The aggregation of platelets plays an important role in the growth of atheromatous plaques, which can lead to coronary, cerebral and peripheral arterial occlusions. In clinical trials, ticagrelor therapy during acute coronary events (unstable angina and myocardial infarction) has been shown to decrease the frequency of recurrence of myocardial infarction and stent thrombosis. Ticagrelor was approved for use in the United States in 2011 and has been used in limited numbers of patients for a limited time only. Current indications are reduction of recurrent cardiovascular events in patients with acute coronary syndromes. Ticagrelor is available in 90 mg tablets under the commercial name Brilinta. The usual maintenance dose is 90 mg twice daily in combination with daily low dose aspirin (<100 mg). Side effects are not common, but can include bleeding (12%), dyspnea (14%), headaches, nausea, diarrhea, hypotension and hypersensitivity reactions. Rare but potentially severe adverse reactions include severe bleeding, rhabdomyolysis, complications of drug-drug interactions, angioedema and hypersensitivity reactions.</p></div><div id="Ticagrelor.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>In several large clinical trials, ticagrelor was not associated with serum enzyme elevations during therapy and no instances of clinically apparent liver injury were reported. While there have been isolated reports of transient and mild serum enzyme elevations during ticagrelor therapy, these have been short lived and asymptomatic. In addition, since marketing and release, there have been no reports of isolated clinically apparent liver injury or jaundice associated with ticagrelor therapy and hepatotoxicity is not mentioned in the product label. On the other hand, there have been several reports of jaundice and liver injury associated with rhabdomyolysis and with thrombotic thrombocytopenic purpura that represented secondary effects of these severe adverse events. Thus, significant liver injury due to ticagrelor occurs but has occurred largely in association with other life-threatening complications.</p><p><a class="def" href="/books/n/livertox/glossary/def-item/glossary.likelihood-score/">Likelihood score</a>: D (possible rare cause of liver injury due to complications of severe allergic reactions or drug-drug interactions).</p></div><div id="Ticagrelor.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>Ticagrelor, unlike clopidogrel, does not require metabolic activation for its antiplatelet effects. Ticagrelor is metabolized in the liver predominantly via CYP 3A4 and it should be used with caution in patients taking CYP 3A4 inhibitors (such as ketoconazole, clarithromycin, atazanavir and nefazodone), which can increase serum levels, or CYP 3A4 inducers (such as rifampin, dexamethasone and phenytoin) which can decrease drug levels.</p></div><div id="Ticagrelor.Outcome_and_Management"><h3>Outcome and Management</h3><p>There is little evidence that ticagrelor can cause liver injury or has any cross sensitivity to other antiplatelet agents, so that switching from clopidogrel or prasugrel after clinically apparent liver injury is probably safe.</p><p>Drug Class: <a href="/books/n/livertox/Anticoagulants/">Antithrombotic Agents</a>, <a href="/books/n/livertox/Anticoagulants/">Antiplatelet Agents</a></p><p>Other Drugs in the Subclass, Antiplatelet Agents: <a href="/books/n/livertox/Aspirin/">Aspirin</a>, <a href="/books/n/livertox/Cangrelor/">Cangrelor</a>, <a href="/books/n/livertox/Clopidogrel/">Clopidogrel</a>, <a href="/books/n/livertox/Dipyridamole/">Dipyridamole</a>, <a href="/books/n/livertox/Prasugrel/">Prasugrel</a>, <a href="/books/n/livertox/Ticlopidine/">Ticlopidine</a>, <a href="/books/n/livertox/Vorapaxar/">Vorapaxar</a></p></div></div><div id="Ticagrelor.PRODUCT_INFORMATION"><h2 id="_Ticagrelor_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><p>
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||
<b>REPRESENTATIVE TRADE NAMES</b>
|
||
</p><p>Ticagrelor – Brilinta®</p><p>
|
||
<b>DRUG CLASS</b>
|
||
</p><p>Antithrombotic Agents</p><p>
|
||
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Ticagrelor" 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="Ticagrelor.CHEMICAL_FORMULA_AND_STRUCTUR"><h2 id="_Ticagrelor_CHEMICAL_FORMULA_AND_STRUCTUR_">CHEMICAL FORMULA AND STRUCTURE</h2><div id="Ticagrelor.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548529/table/Ticagrelor.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Ticagrelor.Tc_lrgtbl__"><table><thead><tr><th id="hd_h_Ticagrelor.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DRUG</th><th id="hd_h_Ticagrelor.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_Ticagrelor.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_Ticagrelor.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_Ticagrelor.Tc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ticagrelor</td><td headers="hd_h_Ticagrelor.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/135207318" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">274693-27-5</a>
|
||
</td><td headers="hd_h_Ticagrelor.Tc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">C23-H28-F2-N6-O4-S</td><td headers="hd_h_Ticagrelor.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/135207318" 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=135207318" alt="image 135207318 in the ncbi pubchem database" /></a>
|
||
</td></tr></tbody></table></div></div></div><div id="Ticagrelor.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Ticagrelor_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 25 September 2020</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Ticagrelor.REF.zimmerman.1999">Zimmerman HJ. Platelet aggregation inhibitors. 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. 641-3.<div><i>(Textbook of hepatotoxicity published in 1999; ticlopidine, but not clopidogrel, prasugrel or ticagrelor is discussed).</i></div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.de_marzio.2013">De Marzio DH, Navarro VJ. Antiplatelet agents. Hepatotoxicity of cardiovascular and antidiabetic drugs: antihypertensives. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, p. 527-8.<div><i>(Review of hepatotoxicity of antiplatelet drugs discusses ticlopidine, clopidogrel and prasugrel, but does not mention ticagrelor).</i></div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.hogg.2018">Hogg K, Weitz JI. Blood coagulation and anticoagulant, fibrinolytic, and antiplatelet drugs. 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. 849-76.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.husted.2006.1038">Husted S, Emanuelsson H, Heptinstall S, Sandset PM, Wickens M, Peters G. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. <span><span class="ref-journal">Eur Heart J. </span>2006;<span class="ref-vol">27</span>:1038–47.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16476694" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16476694</span></a>]<div>
|
||
<i>(Among 200 patients with atherosclerosis treated with one of 4 doses of ticagrelor or clopidogrel for 28 days, inhibition of platelet aggregation was greater with higher doses of ticagrelor and the most common adverse events were bleeding, dyspnea, dizziness and headache; "no notable time- or treatment-related changes in any ... clinical chemistry parameters ... were observed").</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.cannon.2007.1844">Cannon CP, Husted S, Harrington RA, Scirica BM, Emanuelsson H, Peters G, Storey RF. DISPERSE-2 Investigators. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial. <span><span class="ref-journal">J Am Coll Cardiol. </span>2007;<span class="ref-vol">50</span>:1844–51.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17980250" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17980250</span></a>]<div>
|
||
<i>(Among 990 patients with an acute coronary syndrome treated with one of 2 doses of ticagrelor or clopidogrel for 4-12 weeks, bleeding episodes were similar in the three groups [9.8% and 8.0% vs 8.1%]; no mention of ALT elevations or hepatotoxicity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.chalasani.2008.1924">Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. <span><span class="ref-journal">Gastroenterology. </span>2008;<span class="ref-vol">135</span>:1924–34.</span> [<a href="/pmc/articles/PMC3654244/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3654244</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18955056" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18955056</span></a>]<div>
|
||
<i>(Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, none were attributed to antiplatelet agents).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.wallentin.2009.1045">Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, et al. PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. <span><span class="ref-journal">N Engl J Med. </span>2009;<span class="ref-vol">361</span>:1045–57.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19717846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19717846</span></a>]<div>
|
||
<i>(Among 18,624 patients with acute coronary syndrome treated with ticagrelor or clopidogrel, deaths from vascular cases within 12 months were less with ticagrelor [9.8% vs 11.7%], while major bleeding rates were similar [11.6% vs 11.2%]; no mention of hepatotoxicity or ALT elevations).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.mohammad.2010.2265">Mohammad RA, Goldberg T, Dorsch MP, Cheng JW. Antiplatelet therapy after placement of a drug-eluting stent: a review of efficacy and safety studies. <span><span class="ref-journal">Clin Ther. </span>2010;<span class="ref-vol">32</span>:2265–81.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21353100" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21353100</span></a>]<div>
|
||
<i>(Systematic review of studies of antiplatelet therapy after coronary stenting discussed bleeding complications only, no mention of ALT elevations or hepatotoxicity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.reuben.2010.2065">Reuben A, Koch DG, Lee WM., Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. <span><span class="ref-journal">Hepatology. </span>2010;<span class="ref-vol">52</span>:2065–76.</span> [<a href="/pmc/articles/PMC3992250/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3992250</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20949552" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20949552</span></a>]<div>
|
||
<i>(Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none were due to antiplatelet medications).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.anderson.2010.524">Anderson SD, Shah NK, Yim J, Epstein BJ. Efficacy and safety of ticagrelor: a reversible P2Y12 receptor antagonist. <span><span class="ref-journal">Ann Pharmacother. </span>2010;<span class="ref-vol">44</span>:524–37.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20124464" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20124464</span></a>]<div>
|
||
<i>(Systematic review of efficacy and safety of ticagrelor is associated with "no significant changes in laboratory values", with the exception of uric acid).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.held.2011.672">Held C, Asenblad N, Bassand JP, Becker RC, Cannon CP, Claeys MJ, Harrington RA, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (Platelet Inhibition and Patient Outcomes) trial. <span><span class="ref-journal">J Am Coll Cardiol. </span>2011;<span class="ref-vol">57</span>:672–84.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21194870" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21194870</span></a>]<div>
|
||
<i>(Subgroup analysis of 1261 patients who underwent coronary artery bypass grafting and were treated with ticagrelor or clopidogrel; no discussion of ALT elevations or hepatotoxicity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.james.2011.d3527">James SK, Roe MT, Cannon CP, Cornel JH, Horrow J, Husted S, Katus H, et al. PLATO Study Group. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial. <span><span class="ref-journal">BMJ. </span>2011;<span class="ref-vol">342</span>:d3527.</span> [<a href="/pmc/articles/PMC3117310/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3117310</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21685437" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21685437</span></a>]<div>
|
||
<i>(Among 5216 patients with acute coronary syndrome treated with ticagrelor or clopidogrel with a planned noninvasive treatment, cardiovascular death was lower with ticagrelor [12% vs 14.3%], while major bleeding episodes were greater [11.9% vs 10.3%]; no mention of ALT elevations or other adverse events).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.butler.2011.978">Butler K, Teng R. Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with mild hepatic impairment. <span><span class="ref-journal">J Clin Pharmacol. </span>2011;<span class="ref-vol">51</span>:978–87.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20926753" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20926753</span></a>]<div>
|
||
<i>(Pharmacokinetic study in 20 volunteers, 10 with compensated cirrhosis, found minimally higher exposure after a single dose of ticagrelor in patients with liver disease, but not enough to recommend dose adjustment; no side effects or worsening of liver chemistry results).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF14">Ticagrelor (Brilinta)--better than clopidogrel (Plavix)? <span><span class="ref-journal">Med Lett Drugs Ther. </span>2011;<span class="ref-vol">53</span>(1372):69–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21897348" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21897348</span></a>]<div>
|
||
<i>(Concise review of the pharmacology, efficacy and safety of ticagrelor shortly after its approval in the US mentions side effects of bleeding, dyspnea, bradyarrhythmias and increases in uric acid and creatinine [effects probably related to stimulation of adenosine receptors]; no mention of ALT elevations or hepatotoxicity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF15">Antithrombotic drugs. <span><span class="ref-journal">Treat Guidel Med Lett. </span>2011;<span class="ref-vol">9</span>(110):61–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21941228" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21941228</span></a>]<div>
|
||
<i>(Guidelines on use of antiplatelet agents including aspirin, clopidogrel, prasugrel and ticagrelor mentions that ticagrelor was found to be more effective than clopidogrel in one study without an increased rate of bleeding; no mention of other side effects, ALT elevations or hepatotoxicity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.li.2012.87">Li H, Butler K, Yang L, Yang Z, Teng R. Pharmacokinetics and tolerability of single and multiple doses of ticagrelor in healthy Chinese subjects: an open-label, sequential, two-cohort, single-centre study. <span><span class="ref-journal">Clin Drug Investig. </span>2012;<span class="ref-vol">32</span>:87–97.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22168538" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22168538</span></a>]<div>
|
||
<i>(In a pharmacokinetic study of ticagrelor in 26 healthy volunteers, two patients developed asymptomatic serum ALT elevations [1.25 and 3 times ULN] without change in bilirubin or alkaline phosphatase within 3 days of starting ticagrelor and lasting for 10 days after stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.htun.2013.237">Htun WW, Steinhubl SR. Ticagrelor: the first novel reversible P2Y(12) inhibitor. <span><span class="ref-journal">Expert Opin Pharmacother. </span>2013;<span class="ref-vol">14</span>:237–45.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23268703" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23268703</span></a>]<div>
|
||
<i>(Review of pharmacology, efficacy and safety of ticagrelor in comparison to other antiplatelet agents; no mention of hepatotoxicity or ALT elevations during therapy).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.dinicolantonio.2013.5">DiNicolantonio JJ, Serebruany VL. Comparing the safety of ticagrelor versus clopidogrel: insights from the FDA reports. <span><span class="ref-journal">Ther Adv Cardiovasc Dis. </span>2013;<span class="ref-vol">7</span>:5–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23393061" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23393061</span></a>]<div>
|
||
<i>(The FDA analysis of trials of ticagrelor reported that patients with preexisting liver disease were more likely to have serious adverse events on ticagrelor than clopidogrel, including death [3.1% vs 0.9%] and major bleeds [11.2% vs 8.7%], the reasons for which were not clear).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.lindholm.2014.2083">Lindholm D, Varenhorst C, Cannon CP, Harrington RA, Himmelmann A, Maya J, Husted S, et al. Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: results from the PLATO trial. <span><span class="ref-journal">Eur Heart J. </span>2014;<span class="ref-vol">35</span>(31):2083–93.</span> [<a href="/pmc/articles/PMC4132637/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4132637</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24727884" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24727884</span></a>]<div>
|
||
<i>(Retrospective analysis of data from the PLATO trial of ticagrelor vs clopidogrel in 18,624 patients with acute coronary syndrome found similar rates of bleeding with both agents; no mention of ALT elevations or hepatotoxicity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.hern_ndez.2014.231">Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A, Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America: an analysis of published reports. <span><span class="ref-journal">Ann Hepatol. </span>2014;<span class="ref-vol">13</span>:231–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24552865" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24552865</span></a>]<div>
|
||
<i>(Among 176 reports of drug induced liver injury from Latin America published between 1996 and 2012, none were attributed to ticagrelor).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.chalasani.2015.1340">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. <span><span class="ref-journal">Gastroenterology. </span>2015;<span class="ref-vol">148</span>:1340–52.e7.</span> [<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, two were attributed to antithrombotic agents, one to prasugrel and one to dalteparin; none were due to ticagrelor).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.banakh.2017.3801819">Banakh I, Haji K, Kung R, Gupta S, Tiruvoipati R. Severe rhabdomyolysis due to presumed drug interactions between atorvastatin with amlodipine and ticagrelor. <span><span class="ref-journal">Case Rep Crit Care. </span>2017;<span class="ref-vol">2017</span>:3801819. </span> [<a href="/pmc/articles/PMC5463112/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5463112</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28630772" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28630772</span></a>]<div>
|
||
<i>(74 year old woman developed rhabdomyolysis 2 months after starting ticagrelor having been on atorvastatin for years with complications of septic shock, renal failure and acute hepatic necrosis [bilirubin 3.1 to 9.8 mg/dL, 746 to 1605 U/L, Alk P 260 to 325 U/L, INR 1.8 to 2.0, CPK >90,000 IU/L], with prolonged ICU stay but ultimate resolution of renal and liver abnormalities).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.bellosta.2018.25">Bellosta S, Corsini A. Statin drug interactions and related adverse reactions: an update. <span><span class="ref-journal">Expert Opin Drug Saf. </span>2018;<span class="ref-vol">17</span>:25–37.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29058944" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29058944</span></a>]<div>
|
||
<i>(Summary and review of drug-drug interactions including ticagrelor, a CYP3A4 and P-pg substrate and weak inhibitor which can cause an increase in atorvastatin plasma levels).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.wang.2018.e11206">Wang X, Zhang S, Li L, Hua J, Zhu L, Li L, Zhang G. Ticagrelor-induced thrombotic thrombocytopenic purpura: A case report and review of the literature. <span><span class="ref-journal">Medicine (Baltimore). </span>2018;<span class="ref-vol">97</span>:e11206. </span> [<a href="/pmc/articles/PMC6039671/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6039671</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29952973" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29952973</span></a>]<div>
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||
<i>(87 year old man with a history of acute myocardial infarction developed thrombotic thrombocytopenic purpura 2 months after starting ticagrelor [platelets 3,000, hematocrit 22.3%, bilirubin 16.0 mg/dL, ALT 3947 U/L, Alk P 59 U/L, protime 26.3 sec], with spontaneous improvement but recurrence on restarting ticagrelor leading to multiorgan failure and death).</i>
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</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.sch_pke.2019.1524">Schüpke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I, Wöhrle J. Richardt Get al.; ISAR-REACT 5 Trial Investigators. Ticagrelor or prasugrel in patients with acute coronary syndromes. <span><span class="ref-journal">N Engl J Med. </span>2019;<span class="ref-vol">381</span>:1524–34.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31475799" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31475799</span></a>]<div>
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||
<i>(Among 4018 patients with acute coronary syndromes treated with ticagrelor or prasugrel for one year, major cardiovascular events were less with prasugrel [6.9% vs 9.3%], but major bleeding event rates were similar [4.8% vs 5.4%]; no mention of ALT elevations or hepatotoxicity).</i>
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||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.navarese.2020.150">Navarese EP, Khan SU, Kołodziejczak M, Kubica J, Buccheri S, Cannon CP, Gurbel PA, De Servi S, Budaj A, Bartorelli A, Trabattoni D, Ohman EM, Wallentin L, Roe MT, James S. Comparative efficacy and safety of oral P2Y inhibitors in acute coronary syndrome: network meta-analysis of 52 816 patients from 12 randomized trials. <span><span class="ref-journal">Circulation. </span>2020;<span class="ref-vol">142</span>:150–60.</span> [<a href="/pmc/articles/PMC7489363/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7489363</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32468837" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32468837</span></a>]<div>
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<i>(Metaanalysis of 12 randomized controlled trials in 52,816 patients comparing 3 antiplatelet agents found that prasugrel and ticagrelor had lower rates of cardiovascular mortality and stent thrombosis than clopidogrel, but had higher rates of major bleeding episodes; no mention of ALT elevations or hepatotoxicity).</i>
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||
</div></div></li><li><div class="bk_ref" id="Ticagrelor.REF.tarantini.2020">Tarantini G, Mojoli M, Varbella F, Caporale R, Rigattieri S, Andò G, Cirillo P, et al.; DUBIUS Investigators, on behalf of the Italian Society of Interventional Cardiology (SICI-GISE). Timing of oral P2Y inhibitor administration in non-ST elevation acute coronary syndrome. J Am Coll Cardiol 2020: S0735-1097(20)36444-5. Epub ahead of print.<div><i>(Among 1449 patients undergoing coronary angiography treated with prasugrel or ticagrelor, rates of a combined clinical efficacy endpoint were similar in the two groups; no mention of ALT elevations or hepatotoxicity).</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div>
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Epub 2019 Apr 9.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/28325638" ref="ordinalpos=1&linkpos=2&log$=relatedarticles&logdbfrom=pubmed">Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial.</a><span class="source">[Lancet. 2017]</span><div class="brieflinkpop offscreen_noflow">Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Ohman EM, Roe MT, Steg PG, James SK, Povsic TJ, White J, Rockhold F, Plotnikov A, Mundl H, Strony J, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Lancet. 2017 May 6; 389(10081):1799-1808. 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