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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="#__NBK548205_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK548205_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/Docetaxel/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/livertox/Dofetilide/" 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="_NBK548205_"><span class="title" itemprop="name">Docusate</span></h1><p class="small">Last Update: <span itemprop="dateModified">January 9, 2018</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="Docusate.OVERVIEW"><h2 id="_Docusate_OVERVIEW_">OVERVIEW</h2><div id="Docusate.Introduction"><h3>Introduction</h3><p>Docusate is an orally available, over-the-counter laxative and stool softener used to treat or prevent constipation. Docusate has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury with jaundice.</p></div><div id="Docusate.Background"><h3>Background</h3><p>Docusate (dok’ ue sate) is a stool softener and surfactant previously known as dioctyl sodium [or calcium] sulfosuccinate (DSS). Docusate is commonly used to treat or prevent constipation and to promote bowel regularity in hospitalized, bed-bound or immobilized persons. Docusate salts are thought to act as detergents, reducing surface tension of liquids and fatty substances in the intestine, thereby softening stool consistency. The efficacy of docusate in treatment and prevention of constipation has not been well documented. However, extensive experience with its use has documented its safety and tolerability. Docusate has been in use in the U.S. since the 1950s and current indications are for treatment and prevention of constipation. Docusate is available without prescription in capsules of 50, 100, 240 and 250 mg generically and under various brand names such as Colace, Doxidan, Regulex, Silace and Surfak. A liquid formulation for oral use is also available. The typical oral dose is 50 to 300 mg daily until bowel movements are normal. Common side effects include diarrhea, abdominal cramping, nausea, bitter taste and dizziness.</p></div><div id="Docusate.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>Docusate has not been linked to elevations in serum enzyme levels during treatment, although there have been few published studies of its effects of liver tests. There have been no cases of clinically apparent liver injury attributable to docusate published in the literature and, thus, significant liver injury from docusate must be exceedingly 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="Docusate.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>Docusate is metabolized by the liver and undergoes extensive first-pass metabolism to both active and inactive metabolites. Despite its hepatic metabolism and high level of plasma protein binding, it has not been implicated in causing drug-drug interactions. The lack of reported cases of liver injury due to docusate may be due to the low doses of typical therapy.</p><p>Drug Class: Gastrointestinal Agents, Cathartics and Laxatives</p></div></div><div id="Docusate.PRODUCT_INFORMATION"><h2 id="_Docusate_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><div id="Docusate.BPI" class="box"><p>
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<b>REPRESENTATIVE TRADE NAMES</b>
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</p><p>Docusate – Generic, Colace®</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=Docusate" 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="Docusate.CHEMICAL_FORMULA_AND_STRUCTURE"><h2 id="_Docusate_CHEMICAL_FORMULA_AND_STRUCTURE_">CHEMICAL FORMULA AND STRUCTURE</h2><div id="Docusate.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548205/table/Docusate.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Docusate.T1_lrgtbl__"><table><thead><tr><th id="hd_h_Docusate.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">DRUG</th><th id="hd_h_Docusate.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">CAS REGISTRY NO.</th><th id="hd_h_Docusate.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Docusate.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_Docusate.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Docusate</td><td headers="hd_h_Docusate.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/134990636" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">10041-19-7</a>
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</td><td headers="hd_h_Docusate.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">C20-H38-O7-S</td><td headers="hd_h_Docusate.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<div class="graphic"><img src="/books/NBK548205/bin/Docusate_structure.jpg" alt="Docusate chemical structure" /></div>
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</td></tr></tbody></table></div></div></div><div id="Docusate.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Docusate_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 09 January 2018</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Docusate.R1">Zimmerman HJ. Antiemetic and prokinetic compounds. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999: pp. 721.<div><i>(Expert review of hepatotoxicity published in 1999 does not discuss docusate).</i></div></div></li><li><div class="bk_ref" id="Docusate.R2">Sharkey KA, Wallace JL. Treatment of disorders of bowel motility and water flux: anti-emetics; agents used in biliary and pancreatic disease. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1323-50.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Docusate.R3">Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies or chronic constipation: systematic review. Am J Gastroenterol 2005; 100: 936-71. [<a href="https://pubmed.ncbi.nlm.nih.gov/15784043" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15784043</span></a>]<div><i>(Systematic review of the literature for controlled trials of traditional therapies for constipation reported "a paucity of trials for many commonly used agents", including bisacodyl and docusate).</i></div></div></li><li><div class="bk_ref" id="Docusate.R4">Hurdon V, Viola R, Schroder C. How useful is docusate in patients at risk for constipation? A systematic review of the evidence in the chronically ill. J Pain Symptom Manage 2000; 19: 130-6. [<a href="https://pubmed.ncbi.nlm.nih.gov/10699540" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10699540</span></a>]<div><i>(Systematic review of efficacy of docusate for constipation in chronically ill patients identified four studies of docusate vs placebo for 20 to 26 days in doses of 60-480 mg daily, all showing slight effect on stool frequency, but only one documenting normal laboratory test results on treatment).</i></div></div></li><li><div class="bk_ref" id="Docusate.R5">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, no cases were attributed to laxatives).</i></div></div></li><li><div class="bk_ref" id="Docusate.R6">Mueller-Lissner SA, Wald A. Constipation in adults. Clin Evid (Online) 2010; 2010. pii: 0413. [<a href="/pmc/articles/PMC3217654/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3217654</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21418672" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21418672</span></a>]<div><i>(Review of evidence of efficacy of conventional therapies of constipation).</i></div></div></li><li><div class="bk_ref" id="Docusate.R7">Ruston T, Hunter K, Cummings G, Lazarescu A. Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review. Can Oncol Nurs J 2013; 23: 236-46. [<a href="https://pubmed.ncbi.nlm.nih.gov/24428006" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24428006</span></a>]<div><i>(Systematic review of literature on controlled trials of docusate in opioid induced constipation found no articles that met the authors' criteria for medical evidence of efficacy; no discussion of safety).</i></div></div></li><li><div class="bk_ref" id="Docusate.R8">Tarumi Y, Wilson MP, Szafran O, Spooner GR. Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients. J Pain Symptom Manage 2013; 45: 2-13. [<a href="https://pubmed.ncbi.nlm.nih.gov/22889861" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22889861</span></a>]<div><i>(In 74 hospice patients treated with docusate or placebo for 10 days, there were no differences in stool frequency or consistency between the two groups; adverse events were not mentioned).</i></div></div></li><li><div class="bk_ref" id="Docusate.R9">Müller-Lissner S. Pharmacokinetic and pharmacodynamic considerations for the current chronic constipation treatments. Expert Opin Drug Metab Toxicol 2013; 9: 391-401. [<a href="https://pubmed.ncbi.nlm.nih.gov/23425050" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23425050</span></a>]<div><i>(Review of the pharmacology, efficacy and safety of medications for constipation mentions that docusate is commonly used, but "there is apparently no evidence at all that it is better than placebo"; no mention of side effects).</i></div></div></li><li><div class="bk_ref" id="Docusate.R10">Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144: 1419-25. [<a href="https://pubmed.ncbi.nlm.nih.gov/23419359" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23419359</span></a>]<div><i>(In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none were attributed to laxatives).</i></div></div></li><li><div class="bk_ref" id="Docusate.R11">Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [<a href="/pmc/articles/PMC4446235/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4446235</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25754159" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25754159</span></a>]<div><i>(Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to docusate or other over-the-counter laxatives).</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK548205/?report=reader">PubReader</a></li><li><a href="/books/NBK548205/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK548205" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK548205" style="display:none" title="Cite this Page"><div class="bk_tt">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Docusate. 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<a href="https://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pubmed&pubmedfilters=true&term=Docusate+AND+Human%5BMH%5D+AND+(drug+induced+liver+injury+OR+jaundice/CI+OR+bile+duct+diseases/CI+OR+liver/DE+OR+liver+diseases/CI)+AND+(%221900/1/1%22%5BEDat%5D%3A%222999/12/31%22%5BEDat%5D)" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri">Recent References on Docusate: from PubMed.gov</a>
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<a href="https://clinicaltrials.gov/ct2/results?term=Docusate" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri">Trials on Docusate: 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=4863704" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pcsubstance&DbFrom=books&Cmd=Link&LinkName=books_pcsubstance&IdsFromResult=4863704" ref="log$=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=4863704" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/27154771" ref="ordinalpos=1&linkpos=1&log$=relatedarticles&logdbfrom=pubmed">Missed Opportunity to Deprescribe: Docusate for Constipation in Medical Inpatients.</a><span class="source">[Am J Med. 2016]</span><div class="brieflinkpop offscreen_noflow">Missed Opportunity to Deprescribe: Docusate for Constipation in Medical Inpatients.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">MacMillan TE, Kamali R, Cavalcanti RB. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Am J Med. 2016 Sep; 129(9):1001.e1-7. Epub 2016 May 3.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/18454610" ref="ordinalpos=1&linkpos=2&log$=relatedarticles&logdbfrom=pubmed">A comparison of sennosides-based bowel protocols with and without docusate in hospitalized patients with cancer.</a><span class="source">[J Palliat Med. 2008]</span><div class="brieflinkpop offscreen_noflow">A comparison of sennosides-based bowel protocols with and without docusate in hospitalized patients with cancer.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Hawley PH, Byeon JJ. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">J Palliat Med. 2008 May; 11(4):575-81. </em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/22889861" ref="ordinalpos=1&linkpos=3&log$=relatedarticles&logdbfrom=pubmed">Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients.</a><span class="source">[J Pain Symptom Manage. 2013]</span><div class="brieflinkpop offscreen_noflow">Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Tarumi Y, Wilson MP, Szafran O, Spooner GR. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">J Pain Symptom Manage. 2013 Jan; 45(1):2-13. Epub 2012 Aug 11.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/25520993" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Dioctyl Sulfosuccinate or Docusate (Calcium or Sodium) for the Prevention or Management of Constipation: A Review of the Clinical Effectiveness</a><span class="source">[ 2014]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Dioctyl Sulfosuccinate or Docusate (Calcium or Sodium) for the Prevention or Management of Constipation: A Review of the Clinical Effectiveness<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">2014 Jun 26</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/33596159" ref="ordinalpos=1&linkpos=5&log$=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> Rethinking Docusate's Role in Opioid-Induced Constipation: A Critical Analysis of the Evidence.</a><span class="source">[J Pain Palliat Care Pharmacoth...]</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> Rethinking Docusate's Role in Opioid-Induced Constipation: A Critical Analysis of the Evidence.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Engle AL, Winans ARM. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">J Pain Palliat Care Pharmacother. 2021 Mar; 35(1):63-72. 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