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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="#__NBK548021_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK548021_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/Licorice/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/livertox/Linagliptin/" 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="_NBK548021_"><span class="title" itemprop="name">Linaclotide</span></h1><p class="small">Last Update: <span itemprop="dateModified">May 13, 2019</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="Linaclotide.OVERVIEW"><h2 id="_Linaclotide_OVERVIEW_">OVERVIEW</h2><div id="Linaclotide.Introduction"><h3>Introduction</h3><p>Linaclotide is small peptide agonist of guanylate cyclase C receptors in the intestine and is used orally as treatment of chronic constipation and irritable bowel syndrome. Linaclotide has not been linked to serum enzyme elevations during treatment or to episodes of clinically apparent liver injury.</p></div><div id="Linaclotide.Background"><h3>Background</h3><p>Linaclotide (lin ak’ loe tide) is 14 amino acid peptide that acts as an agonist of the guanylate cyclase C receptors in the intestine. Activation of this receptor by linaclotide increases cyclic guanosine monophosphate levels which lead to an increase in secretion of chloride and bicarbonate into the intestinal lumen, thus increasing fluid secretion and promoting intestinal transit. Linaclotide acts locally on the luminal side of enterocytes in the upper intestine and is minimally absorbed. Several clinical trials have shown that linaclotide increases the number of spontaneous bowel movements, improves stool consistency and can alleviate symptoms of chronic constipation including the constipation of irritable bowel syndrome. Linaclotide was approved for use in the United States in 2012 for irritable bowel syndrome with constipation as well as idiopathic chronic constipation. Linaclotide is available in capsules of 72, 145 and 290 mcg under the brand name Linzess. The recommended dose for chronic idiopathic constipation is 72 or 145 mcg once daily and for irritable bowel syndrome with constipation is 290 mcg once daily. It is contraindicated in children below the age of 6 years and is not recommended for use in children below the age of 18 years. Side effects include diarrhea (~20%), abdominal pain, bloating, flatulence and headache. Rare but potentially severe adverse events include severe dehydration particularly in children.</p></div><div id="Linaclotide.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>In clinical trials, linaclotide therapy was not associated with significant changes in serum enzyme levels or episodes of clinically apparent liver injury. Minor transient <a class="def" href="/books/n/livertox/glossary/def-item/glossary.alanine-aminotransferase-alt-/">ALT</a> elevations arose in <1% of persons receiving long-term linaclotide therapy for constipation. Since its approval and marketing, there have been no reports of symptomatic serum aminotransferase elevations or clinically apparent liver injury with jaundice attributable to linaclotide. Thus, liver injury from linaclotide must be rare if it occurs at all.</p><p><a class="def" href="/books/n/livertox/glossary/def-item/glossary.likelihood-score/">Likelihood score</a>: E (unlikely cause of clinically apparent liver injury).</p></div><div id="Linaclotide.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>Linaclotide is largely active on the epithelial cells in the intestinal tract and has minimal absorption. The lack of systemic absorption and the low doses used (in microgram amounts) may account for its lack of liver injury.</p><p>Drug Class: <a href="/books/n/livertox/GastrointestinalAgen/">Gastrointestinal Agents</a>, Drugs for Constipation, Irritable Bowel Syndrome Agents</p></div></div><div id="Linaclotide.PRODUCT_INFORMATION"><h2 id="_Linaclotide_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><div id="Linaclotide.BPI" class="box"><p>
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<b>REPRESENTATIVE TRADE NAMES</b>
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</p><p>Linaclotide – Generic, Linzess®</p><p>
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<b>DRUG CLASS</b>
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</p><p>Gastrointestinal Agents</p><p>
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<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Linaclotide" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
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</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></div><div id="Linaclotide.CHEMICAL_FORMULA_AND_STRUCTU"><h2 id="_Linaclotide_CHEMICAL_FORMULA_AND_STRUCTU_">CHEMICAL FORMULA AND STRUCTURE</h2><div id="Linaclotide.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548021/table/Linaclotide.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Linaclotide.T1_lrgtbl__"><table><thead><tr><th id="hd_h_Linaclotide.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">DRUG</th><th id="hd_h_Linaclotide.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">CAS REGISTRY NO.</th><th id="hd_h_Linaclotide.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Linaclotide.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_Linaclotide.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Linaclotide</td><td headers="hd_h_Linaclotide.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://pubchem.ncbi.nlm.nih.gov/substance/135264508" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">851199-59-2</a>
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</td><td headers="hd_h_Linaclotide.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">C59-H79-N15-O23-S6</td><td headers="hd_h_Linaclotide.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<div class="graphic"><img src="/books/NBK548021/bin/Linaclotide_structure.jpg" alt="Linaclotide Chemical Structure" /></div>
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</td></tr></tbody></table></div></div></div><div id="Linaclotide.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Linaclotide_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 13 May 2019</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Linaclotide.R1">Zimmerman HJ. Laxatives. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999: pp. 721-3.<div><i>(Expert review of hepatotoxicity of laxatives published in 1999 with discussion of oxyphenisatin and other agents, but not linaclotide).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R2">Sharkey KA, McNaughton WK. Treatment of disorders of bowel motility and water flux: anti-emetics; agents used in biliary and pancreatic disease. 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. 921-44.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R3"><a href="https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202811Orig1s000MedR.pdf" 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/drugsatfda_docs<wbr style="display:inline-block"></wbr>/nda/2012/202811Orig1s000MedR.pdf</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 ALT elevations above 3 times ULN occurred in 0.5% of 3173 patients in long-term safety trials of linaclotide, but that no cases of ALT elevations with jaundice were reported).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R4">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. Gastroenterology 2008; 135: 1924-34. [<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 agents used for constipation or irritable bowel syndrome [IBS]).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R5">Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. [<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 attributed to gastrointestinal agents, laxatives or drugs for IBS).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R6">Shah E, Kim S, Chong K, Lembo A, Pimentel M. Evaluation of harm in the pharmacotherapy of irritable bowel syndrome. Am J Med 2012; 125: 381-93. [<a href="https://pubmed.ncbi.nlm.nih.gov/22444104" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22444104</span></a>]<div><i>(Systematic review of adverse side effects of drugs used to treat irritable bowel syndrome including lubiprostone, but not linaclotide).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R7">Lembo AJ, Schneier HA, Shiff SJ, Kurtz CB, MacDougall JE, Jia XD, Shao JZ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med 2011; 365: 527-36. [<a href="https://pubmed.ncbi.nlm.nih.gov/21830967" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21830967</span></a>]<div><i>(Among 1276 patients with chronic constipation treated with linaclotide or placebo for 12 weeks, diarrhea was the most common side effect [14-16% vs 4.7% in controls] and "there were no clinically significant differences in...blood chemistry values" between the two groups).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R8">Rao S, Lembo AJ, Shiff SJ, Lavins BJ, Currie MG, Jia XD, Shi K, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol 2012; 107: 1714-24. [<a href="/pmc/articles/PMC3504311/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3504311</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22986440" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22986440</span></a>]<div><i>(Among 800 patients with constipation predominant IBS treated with linaclotide or placebo for 12 weeks, the most common side effect was diarrhea [20% vs 3.5% with placebo] and there were "no clinically significant differences between the linaclotide and placebo groups in the incidence of abnormal laboratory parameters").</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R9">Chey WD, Lembo AJ, Lavins BJ, Shiff SJ, Kurtz CB, Currie MG, MacDougall JE, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol 2012; 107: 1702-12. [<a href="https://pubmed.ncbi.nlm.nih.gov/22986437" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22986437</span></a>]<div><i>(Among 804 patients with IBS and constipation treated for 12 weeks, pain, bloating and bowel symptoms were improved with linaclotide compared to placebo therapy and side effects were similar except for diarrhea with linaclotide, and "there were no clinically meaningful differences...in the incidence of abnormal laboratory parameters").</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R10">Linaclotide (Linzess) for constipation. Med Lett Drugs Ther 2012; 54 (1403): 91-2. [<a href="https://pubmed.ncbi.nlm.nih.gov/23183319" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23183319</span></a>]<div><i>(Concise summary of the mechanism of action, efficacy and safety of linaclotide for constipation shortly after its approval in the United States; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R11">Quigley EM, Tack J, Chey WD, Rao SS, Fortea J, Falques M, Diaz C, et al. Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpoints. Aliment Pharmacol Ther 2013; 37: 49-61. [<a href="https://pubmed.ncbi.nlm.nih.gov/23116208" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23116208</span></a>]<div><i>(Reanalysis of controlled trials of linaclotide for constipation predominant IBS [Rao 2012, Chey 2012] using different endpoints; no further discussion of side effects).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R12">Berntgen M, Enzmann H, Schabel E, Prieto Yerro C, Gómez-Outes A, Salmonson T, Musaus J. Linaclotide for treatment of irritable bowel syndrome--the view of European regulators. Dig Liver Dis 2013; 45: 724-6. [<a href="https://pubmed.ncbi.nlm.nih.gov/23701993" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23701993</span></a>]<div><i>(Review of the efficacy and safety of linaclotide in IBS which led to the approval of its use by the European Medicines Agency). </i></div></div></li><li><div class="bk_ref" id="Linaclotide.R13">Lacy BE, Schey R, Shiff SJ, Lavins BJ, Fox SM, Jia XD, Blakesley RE, et al. Linaclotide in chronic idiopathic constipation patients with moderate to severe abdominal bloating: a randomized, controlled trial. PLoS One 2015; 10: e0134349. [<a href="/pmc/articles/PMC4519259/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4519259</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26222318" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26222318</span></a>]<div><i> (Among 483 patients with chronic idiopathic constipation and abdominal bloating treated with linaclotide [145 or 290 mcg] or placebo once daily for 12 weeks, abdominal symptoms improved more frequently while adverse event rates were slightly higher with linaclotide, diarrhea occurring in 6% and 17% vs 2.3% with placebo; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R14">Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52. [<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, one case was attributed to metoclopramide, but none to other prokinetic agents or drugs for chronic idiopathic constipation).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R15">Black CJ, Ford AC. Chronic idiopathic constipation in adults: epidemiology, pathophysiology, diagnosis and clinical management. Med J Aust 2018; 209: 86-91. [<a href="https://pubmed.ncbi.nlm.nih.gov/29996755" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29996755</span></a>]<div><i>(Review of the role of guanylate cyclase C in gastrointestinal physiology and the biologic basis for the use of guanylate cyclase receptor agonists as therapy of gastrointestinal disorders).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R16">Waldman SA, Camilleri M. Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders. Gut 2018; 67: 1543-52. [<a href="/pmc/articles/PMC6204952/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6204952</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29563144" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29563144</span></a>]<div><i>(Review of the definition, diagnosis, epidemiology, pathophysiology, clinical features and management and drug therapy of chronic idiopathic constipation). </i></div></div></li><li><div class="bk_ref" id="Linaclotide.R17">Schoenfeld P, Lacy BE, Chey WD, Lembo AJ, Kurtz CB, Reasner DS, Bochenek W, et al. Low-dose linaclotide (72 μg) for chronic idiopathic constipation: a 12-week, randomized, double-blind, placebo-controlled trial. Am J Gastroenterol 2018; 113: 105-14. [<a href="/pmc/articles/PMC5770595/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5770595</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29091082" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29091082</span></a>]<div><i>(Among 1223 patients with chronic idiopathic constipation treated with linaclotide [72 or 145 mcg] or placebo once daily for 12 weeks, overall response rates were higher with linaclotide [13% vs 4.7%] and the major side effect was diarrhea [19% and 22% vs 7%] and there were no hepatic serious adverse events and no mention of ALT elevations).</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R18">Nee JW, Johnston JM, Shea EP, Walls CE, Tripp K, Shiff S, Fox SM, et al. Safety and tolerability of linaclotide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: pooled phase 3 analysis. Expert Rev Gastroenterol Hepatol 2019; 13: 397-406. [<a href="https://pubmed.ncbi.nlm.nih.gov/30791771" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30791771</span></a>]<div><i>(Among 3853 adults evaluated in a pooled safety analysis of placebo-controlled trials of linaclotide therapy of chronic idiopathic constipation, adverse events occurring more frequently with linaclotide were diarrhea [17-20%] and abdominal pain [4-7%], and "laboratory values showed no consequential changes from baseline").</i></div></div></li><li><div class="bk_ref" id="Linaclotide.R19">Fukudo S, Miwa H, Nakajima A, Kinoshita Y, Kosako M, Hayashi K, Akiho H, et al. High-dose linaclotide is effective and safe in patients with chronic constipation: A phase III randomized, double-blind, placebo-controlled study with a long-term open-label extension study in Japan. Neurogastroenterol Motil 2019; 31: e13487. [<a href="/pmc/articles/PMC7379198/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7379198</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30353619" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30353619</span></a>]<div><i>(Among 186 Japanese adults with chronic constipation treated with linaclotide [500 mcg daily] in a 4 week placebo controlled trial followed by 52 weeks of open-label therapy, the most frequent adverse event was diarrhea [13% vs 1%], but there were no hepatic serious adverse events and "no clinically significant differences in hematologic or blood chemical results").</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div>
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<a href="https://clinicaltrials.gov/ct2/results?term=Linaclotide" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri">Trials on Linaclotide: from ClinicalTrials.gov</a>
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</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=4855730" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pcsubstance&DbFrom=books&Cmd=Link&LinkName=books_pcsubstance&IdsFromResult=4855730" ref="log$=recordlinks">PubChem Substance</a><div class="brieflinkpop offscreen_noflow">Related PubChem Substances</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=4855730" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20863829" ref="ordinalpos=1&linkpos=1&log$=relatedarticles&logdbfrom=pubmed">Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit.</a><span class="source">[Eur J Pharmacol. 2010]</span><div class="brieflinkpop offscreen_noflow">Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Busby RW, Bryant AP, Bartolini WP, Cordero EA, Hannig G, Kessler MM, Mahajan-Miklos S, Pierce CM, Solinga RM, Sun LJ, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Eur J Pharmacol. 2010 Dec 15; 649(1-3):328-35. Epub 2010 Sep 20.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/23090647" ref="ordinalpos=1&linkpos=2&log$=relatedarticles&logdbfrom=pubmed">Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.</a><span class="source">[J Pharmacol Exp Ther. 2013]</span><div class="brieflinkpop offscreen_noflow">Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Busby RW, Kessler MM, Bartolini WP, Bryant AP, Hannig G, Higgins CS, Solinga RM, Tobin JV, Wakefield JD, Kurtz CB, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">J Pharmacol Exp Ther. 2013 Jan; 344(1):196-206. Epub 2012 Oct 22.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20307554" ref="ordinalpos=1&linkpos=3&log$=relatedarticles&logdbfrom=pubmed">Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract.</a><span class="source">[Life Sci. 2010]</span><div class="brieflinkpop offscreen_noflow">Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Bryant AP, Busby RW, Bartolini WP, Cordero EA, Hannig G, Kessler MM, Pierce CM, Solinga RM, Tobin JV, Mahajan-Miklos S, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Life Sci. 2010 May 8; 86(19-20):760-5. Epub 2010 Mar 20.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/28083815" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Optimizing the Use of Linaclotide in Patients with Constipation-Predominant Irritable Bowel Syndrome: An Expert Consensus Report.</a><span class="source">[Adv Ther. 2017]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Optimizing the Use of Linaclotide in Patients with Constipation-Predominant Irritable Bowel Syndrome: An Expert Consensus Report.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Rey E, Mearin F, Alcedo J, Ciriza C, Delgado-Aros S, Freitas T, Mascarenhas M, Mínguez M, Santos J, Serra J. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Adv Ther. 2017 Mar; 34(3):587-598. Epub 2017 Jan 12.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/24939497" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome.</a><span class="source">[Am J Health Syst Pharm. 2014]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Love BL, Johnson A, Smith LS. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Am J Health Syst Pharm. 2014 Jul 1; 71(13):1081-91. </em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=31643353" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=31643353" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67c8e01dab82281a8039d9fa">Linaclotide - LiverTox</a><div class="ralinkpop offscreen_noflow">Linaclotide - LiverTox<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67c8e01cf4a390645e2ed745">Licorice - LiverTox</a><div class="ralinkpop offscreen_noflow">Licorice - LiverTox<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67c8e01ba68b6b5afc71e06f">L-Glutamine - LiverTox</a><div class="ralinkpop offscreen_noflow">L-Glutamine - LiverTox<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67c8e01af4a390645e2ed375">Levorphanol - LiverTox</a><div class="ralinkpop offscreen_noflow">Levorphanol - LiverTox<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67c8e019ab82281a8039c327">Levofloxacin - LiverTox</a><div class="ralinkpop offscreen_noflow">Levofloxacin - LiverTox<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
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<p class="address_footer text-white">National Library of Medicine<br />
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<a href="https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/@38.9959508,-77.101021,17z/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323" class="text-white" target="_blank" rel="noopener noreferrer">8600 Rockville Pike<br />
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Bethesda, MD 20894</a></p>
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<p><a href="https://www.nlm.nih.gov/web_policies.html" class="text-white">Web Policies</a><br />
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<a href="https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office" class="text-white">FOIA</a><br />
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<a href="https://www.hhs.gov/vulnerability-disclosure-policy/index.html" class="text-white" id="vdp">HHS Vulnerability Disclosure</a></p>
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</div>
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<div class="col-lg-3 col-12 centered-lg">
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<p><a class="supportLink text-white" href="https://support.nlm.nih.gov/">Help</a><br />
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<a href="https://www.nlm.nih.gov/accessibility.html" class="text-white">Accessibility</a><br />
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<a href="https://www.nlm.nih.gov/careers/careers.html" class="text-white">Careers</a></p>
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<div class="row">
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<a class="text-white" href="//www.nlm.nih.gov/">NLM</a>
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||
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<li>
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||
<a class="text-white" href="https://www.nih.gov/">NIH</a>
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<li>
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<a class="text-white" href="https://www.hhs.gov/">HHS</a>
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<li>
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<a class="text-white" href="https://www.usa.gov/">USA.gov</a>
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