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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="Zinc" /><meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases" /><meta name="citation_date" content="2020/07/25" /><meta name="citation_pmid" content="31643536" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK548211/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Zinc" /><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="2020/07/25" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK548211/" /><meta name="description" content="Zinc is an essential mineral and heavy metal that is included in most over-the-counter multivitamin and mineral supplements, and is used therapeutically in higher doses because of its ability to block copper absorption as maintenance therapy of Wilson disease. Zinc has not been associated with worsening of serum enzyme elevations during therapy or with clinically apparent liver injury." /><meta name="og:title" content="Zinc" /><meta name="og:type" content="book" /><meta name="og:description" content="Zinc is an essential mineral and heavy metal that is included in most over-the-counter multivitamin and mineral supplements, and is used therapeutically in higher doses because of its ability to block copper absorption as maintenance therapy of Wilson disease. Zinc has not been associated with worsening of serum enzyme elevations during therapy or with clinically apparent liver injury." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK548211/" /><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/Zinc/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK548211/" /><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" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} </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">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>
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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></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="_NBK548211_"><span class="title" itemprop="name">Zinc</span></h1><p class="small">Last Update: <span itemprop="dateModified">July 25, 2020</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="Zinc.OVERVIEW"><h2 id="_Zinc_OVERVIEW_">OVERVIEW</h2><div id="Zinc.Introduction"><h3>Introduction</h3><p>Zinc is an essential mineral and heavy metal that is included in most over-the-counter multivitamin and mineral supplements, and is used therapeutically in higher doses because of its ability to block copper absorption as maintenance therapy of Wilson disease. Zinc has not been associated with worsening of serum enzyme elevations during therapy or with clinically apparent liver injury.</p></div><div id="Zinc.Background"><h3>Background</h3><p>Zinc is an essential trace element that is found in many human enzymes and transcription factors. The recommended dietary allowance is 8 mg per day for women and 11 mg for men. Zinc is widely present in foods, and the typical Western diet has adequate concentrations, the highest levels being found in shellfish and red meats. Zinc deficiency is usually due to malnutrition and reduced dietary intake, but can also occur with strict vegetarian diets. Zinc deficiency is not uncommon in developing countries, but severe deficiencies are rare. Zinc deficiency can be accompanied by growth retardation, infertility, dysgeusia, diarrhea, dermatitis, glossitis, behavioral changes, depression and mental clouding. The recommended daily allowance of zinc is 15 mg per day in men and 12 mg in women, with higher levels recommended for pregnant or lactating women.</p><p>High doses of oral zinc interfere with the absorption of copper and iron, and supplementation above the RDA can cause copper deficiency. Because of its effects on copper balance, zinc has been used to treat Wilson disease, particularly as maintenance therapy once copper levels have been reduced with chelating agents. Wilson disease is a caused by inherited mutation in the ATPase7B gene, which encodes a hepatic enzyme responsible for the transmembrane transport and excretion of copper. The metabolic defect leads to accumulation of free copper in liver and blood and secondarily in other organs, particularly brain and kidney. The disease usually presents in childhood or adolescence with neurologic syndromes, signs of advanced liver disease and hemolytic anemia. Zinc is a unique approach to the treatment of Wilson disease in that it interferes with dietary absorption (probably by increasing intestinal metallothionein), rather than decreasing tissue levels by chelation. Zinc acetate is approved for use in the United States as maintenance therapy of Wilson disease and is available in capsules of 25 and 50 mg under the brand name Galzin. Other zinc formulations have been used to treat Wilson disease, including zinc sulfate and zinc gluconate (Gluzin), but these have not been formally approved for this indication. The recommended dose is 25 to 50 mg two to three times daily. Zinc when given only once daily has little or no effect on copper balance, and is not recommended. Zinc is generally well tolerated, but when given in high doses up to 10% of patients initially have abdominal pains or gastrointestinal intolerance which can require dose adjustment or discontinuation. Long term therapy can potentially lead to copper deficiency.</p><p>Zinc overdose has been described and is usually due to ingestion of coins, metallic objects or zinc soldering solutions and rarely to suicidal overdose. Symptoms include rapid onset of epigastric pain, nausea and vomiting and diarrhea, followed by lethargy, dizziness, ataxia, confusion and coma. With high doses, patients develop hypotension, metabolic acidosis and hemolytic anemia that can be severe and life-threatening. Liver injury is generally mild and arises after a day or two. Nevertheless, cases with jaundice, cholestasis and hepatic failure have been described. Therapy of acute zinc overdose generally rests upon hydration, gastric lavage or whole bowel irrigation, correction of metabolic acidosis and anemia and zinc chelation with dimercaprol or EDTA infusions.</p></div><div id="Zinc.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>In case series and small trials of zinc therapy in patients with Wilson disease, adverse events have included gastrointestinal upset, but serum enzyme elevations and clinically apparent liver injury were not reported. Patients with Wilson disease frequently have liver injury and, in most case series, zinc therapy has been associated with slow improvement in the hepatic manifestations. Occasional patients with Wilson disease who are switched from penicillamine to zinc therapy develop mild elevations in serum aminotransferase levels, but these are more likely due to worsening control of copper balance and the underlying Wilson disease rather than direct hepatotoxicity of zinc.</p><p>Zinc overdose can be associated with liver injury, jaundice and even hepatic failure, usually arising after several days and resembling injury from copper or iron overdose. The injury is clearly direct toxicity.</p><p>Likelihood score: E (unlikely cause of clinically apparent liver injury in normal therapeutic doses).</p><p>Drug Class: <a href="/books/n/livertox/TraceElementsAndMeta/">Trace Elements and Metals</a>; <a href="/books/n/livertox/ChelatingAgents/">Chelating Agents</a>, <a href="/books/n/livertox/WilsonDiseaseAgents/">Wilson Disease Agents</a></p><p>Other Drugs in the Subclass, Wilson Disease: <a href="/books/n/livertox/Dimercaprol/">Dimercaprol</a>, <a href="/books/n/livertox/Penicillamine/">Penicillamine</a>, <a href="/books/n/livertox/Trientine/">Trientine</a></p></div></div><div id="Zinc.PRODUCT_INFORMATION"><h2 id="_Zinc_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><p>
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<b>REPRESENTATIVE TRADE NAMES</b>
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</p><p>Zinc – Generic, Galzin®</p><p>
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<b>DRUG CLASS</b>
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</p><p>Trace Elements and Metals; Chelating Agents</p><p>
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<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Zinc" 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 id="Zinc.CHEMICAL_FORMULA_AND_STRUCTURE"><h2 id="_Zinc_CHEMICAL_FORMULA_AND_STRUCTURE_">CHEMICAL FORMULA AND STRUCTURE</h2><div id="Zinc.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548211/table/Zinc.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Zinc.Tc_lrgtbl__"><table><thead><tr><th id="hd_h_Zinc.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DRUG</th><th id="hd_h_Zinc.Tc_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CAS REGISTRY NO.</th><th id="hd_h_Zinc.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_Zinc.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_Zinc.Tc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Zinc</td><td headers="hd_h_Zinc.Tc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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||
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/134988678" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">7440-66-6</a>
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||
</td><td headers="hd_h_Zinc.Tc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Zn</td><td headers="hd_h_Zinc.Tc_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Zn</td></tr></tbody></table></div></div></div><div id="Zinc.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Zinc_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 25 July 2020</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Zinc.REF.zimmerman.1999">Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.<div><i>(Review of hepatotoxicity published in 1999; zinc is not discussed).</i></div></div></li><li><div class="bk_ref" id="Zinc.REF.kaplowitz.2013">Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013.<div><i>(Textbook on hepatotoxicity; agents for Wilson disease are not discussed).</i></div></div></li><li><div class="bk_ref" id="Zinc.REF.byrns.2018">Byrns MC, Penning TM. Treatment of metal exposure. Environmental toxicology: carcinogens and heavy metals. 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. 1311-5.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Zinc.REF.murphy.1970.2119">Murphy JV. Intoxication following ingestion of elemental zinc. <span><span class="ref-journal">JAMA. </span>1970;<span class="ref-vol">212</span>:2119–20.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/5467786" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5467786</span></a>]<div>
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||
<i>(16 year old boy ingested 12 g of elemental zinc to help healing of a skin laceration and developed lethargy, light-headedness and ataxia which responded to hydration and dimercaprol [BAL] therapy; serum aminotransferase and bilirubin levels were normal).</i>
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</div></div></li><li><div class="bk_ref" id="Zinc.REF.brocks.1977.1390">Brocks A, Reid H, Glazer G. Acute intravenous zinc poisoning. <span><span class="ref-journal">Br Med J. </span>1977;<span class="ref-vol">1</span>(6073):1390–1.</span> [<a href="/pmc/articles/PMC1606903/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1606903</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/405076" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 405076</span></a>]<div>
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||
<i>(72 year old woman on total parenteral nutrition was given an overdose of zinc sulfate [7.4 g] and she developed hypotension, diarrhea, vomiting, oliguria and jaundice with a cholestatic pattern that slowly resolved, but she died of pneumonia 47 days later).</i>
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||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.stowe.1978.270">Stowe CM, Nelson R, Werdin R, Fangmann G, Fredrick P, Weaver G, Arendt TD. Zinc phosphide poisoning in dogs. <span><span class="ref-journal">J Am Vet Med Assoc. </span>1978;<span class="ref-vol">173</span>:270.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/689968" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 689968</span></a>]<div>
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<i>(Six cases of zinc toxicity in dogs due to zinc phosphide, a rodenticide, presenting with malodor, tremors, rigidity and seizures; no mention of liver injury).</i>
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||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.potter.1981.267">Potter JL. Acute zinc chloride ingestion in a young child. <span><span class="ref-journal">Ann Emerg Med. </span>1981;<span class="ref-vol">10</span>:267–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/6784612" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6784612</span></a>]<div>
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<i>(28 month old boy ingested 4 ounces of soldering flux [20% zinc chloride] and rapidly developed vomiting and lethargy followed by metabolic acidosis [zinc 1,644 μg/dL, AST 48 U/L, Alk P 197 U/L], recovering within 2 days with hydration and EDTA infusions).</i>
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||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.chobanian.1981.91">Chobanian SJ. Accidental ingestion of liquid zinc chloride: local and systemic effects. <span><span class="ref-journal">Ann Emerg Med. </span>1981;<span class="ref-vol">10</span>:91–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/6784611" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6784611</span></a>]<div>
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<i>(24 year old man accidentally ingested a zinc chloride solution with immediate vomiting and burning pain which resolved within 3 days with hydration and EDTA therapy; serum bilirubin and liver enzymes remaining normal).</i>
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||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.hornfeldt.1984.214">Hornfeldt CS, Koepke TE. A case of suspected zinc toxicity in a dog. <span><span class="ref-journal">Vet Hum Toxicol. </span>1984;<span class="ref-vol">26</span>(3):214.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/6610246" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6610246</span></a>]</div></li><li><div class="bk_ref" id="Zinc.REF.allen.1983.363">Allen JG, Masters HG, Peet RL, Mullins KR, Lewis RD, Skirrow SZ, Fry J. Zinc toxicity in ruminants. <span><span class="ref-journal">J Comp Pathol. </span>1983;<span class="ref-vol">93</span>:363–77.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/6886083" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6886083</span></a>]<div>
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||
<i>(In sheep and cattle, zinc toxicity can arise from use of galvanized troughs or zinc containing fertilizers or fungicides, presenting with diarrhea and vomiting, weakness and jaundice and death in severely affected animals, autopsies showing centrolobular [zone 3] hepatic necrosis).</i>
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||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.ulmer.1977.318">Ulmer DD. Trace elements. <span><span class="ref-journal">N Engl J Med. </span>1977;<span class="ref-vol">297</span>:318–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/876314" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 876314</span></a>]<div>
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<i>(Brief review of trace elements, their metabolic roles, deficiencies and toxicities).</i>
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||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.hoogenraad.1978.1262">Hoogenraad TU, Van den Hamer CJ, Koevoet R, Korver EG. Oral zinc in Wilson's disease. <span><span class="ref-journal">Lancet. </span>1978;<span class="ref-vol">2</span>(8102):1262.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/82772" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 82772</span></a>]<div>
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<i>(16 year old with Wilson disease had cupruresis on penicillamine after failure during zinc therapy, although he had no clinical improvement until zinc was reintroduced).</i>
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||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.brewer.1983.314">Brewer GJ, Hill GM, Prasad AS, Cossck ZT, Rabbani P. Oral zinc therapy for Wilson’s disease. <span><span class="ref-journal">Ann Intern Med. </span>1983;<span class="ref-vol">99</span>:314–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/6614680" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6614680</span></a>]<div>
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<i>(5 patients [25-34 years old, 3 men, 2 women] with stable Wilson disease after penicillamine therapy underwent careful copper balance studies while on zinc therapy alone, demonstrating a negative copper balance largely due to increased fecal loss).</i>
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||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.hoogenraad.1983.356">Hoogenraad TU, Van den Hamer CJ. 3 years of continuous oral zinc therapy in 4 patients with Wilson's disease. <span><span class="ref-journal">Acta Neurol Scand. </span>1983;<span class="ref-vol">67</span>:356–64.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/6613522" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6613522</span></a>]<div>
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<i>(4 patients [17 to 46 year old men] with Wilson disease previously treated with penicillamine were treated with oral zinc for at least 3 years and all showed clinical improvement and no adverse events, including no changes in liver tests during zinc therapy).</i>
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||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.hill.1986.344">Hill GM, Brewer GJ, Juni JE, Prasad AS, Dick RD. Treatment of Wilson's disease with zinc. II. Validation of oral 64copper with copper balance. <span><span class="ref-journal">Am J Med Sci. </span>1986;<span class="ref-vol">292</span>:344–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3799705" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3799705</span></a>]<div>
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||
<i>(Assessment of copper update using a radioactive copper uptake study demonstrated that patients with Wilson disease on zinc have a low [<1%], while those on no therapy or on penicillamine or trientine had normal update levels [~6%]).</i>
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||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.breitschwerdt.1986.109">Breitschwerdt EB, Armstrong PJ, Robinette CL, Dillman RC, Karl ML, Lowry EC. Three cases of acute zinc toxicosis in dogs. <span><span class="ref-journal">Vet Hum Toxicol. </span>1986;<span class="ref-vol">28</span>:109–17.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3705436" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3705436</span></a>]<div>
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<i>(3 dogs with zinc toxicity, 2 from swallowing zinc nuts and one from licking zinc oxide ointment, presenting with vomiting, fever, pallor and jaundice with severe hemolytic anemia [bilirubin 1.7-14.9 mg/dL, ALT 143-159 U/L, Alk P 448-5400 U/L], 2 recovering and one dying of anemia and sepsis).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.torrance.1987.443">Torrance AG, Fulton RB Jr. Zinc-induced hemolytic anemia in a dog. <span><span class="ref-journal">J Am Vet Med Assoc. </span>1987;<span class="ref-vol">191</span>:443–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3654320" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3654320</span></a>]<div>
|
||
<i>(1 year old Yorkie developed diarrhea, vomiting, fever and “depression” with severe anemia [hematocrit 15%] after ingesting a zinc nut from his cage [bilirubin 18.9 mg/dL, Alk P 1262 U/L], recovering after endoscopic removal of object).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.hill.1987.522">Hill GM, Brewer GJ, Prasad AS, Hydrick CR, Hartmann DE. Treatment of Wilson's disease with zinc. I. Oral zinc therapy regimens. <span><span class="ref-journal">Hepatology. </span>1987;<span class="ref-vol">7</span>:522–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3570163" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3570163</span></a>]<div>
|
||
<i>(Copper balance studies in 14 patients with previously treated Wilson disease showed a negative copper balance while on zinc [100-150 mg daily in 2-4 separate doses] compared to high positive copper balance in 3 patients on no therapy; no adverse events noted).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.hoogenraad.1987.137">Hoogenraad TU, Van Hattum J, Van den Hamer CJ. Management of Wilson’s disease with zinc sulphate: experience in a series of 27 patients. <span><span class="ref-journal">J Neurol Sci. </span>1987;<span class="ref-vol">77</span>:137–46.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3819764" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3819764</span></a>]<div>
|
||
<i>(Among 27 Dutch patients [ages 11 to 38 years] with Wilson disease treated with zinc sulfate for periods of 1 month to 27 years, 1 died of hepatic failure within the first month, the others all improved with normalization of free serum copper levels and no adverse events).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.burkhart.1990.1167">Burkhart KK, Kulig KW, Rumack B. Whole-bowel irrigation as treatment for zinc sulfate overdose. <span><span class="ref-journal">Ann Emerg Med. </span>1990;<span class="ref-vol">19</span>:1167–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1977339" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1977339</span></a>]<div>
|
||
<i>(16 year old boy ingested 50 zinc sulfate tablets in a suicide attempt and was treated with emetics and whole bowel irrigation, with recovery in 2 days and no mention of liver injury or enzyme elevations).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.broun.1990.1441">Broun ER, Greist A, Tricot G, Hoffman R. Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression. <span><span class="ref-journal">JAMA. </span>1990;<span class="ref-vol">264</span>:1441–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2094240" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2094240</span></a>]<div>
|
||
<i>(Two patients developed anemia due to zinc; a 31 year old schizophrenic man swallowed multiple coins and presented with nausea and abdominal pain with subsequent severe anemia resolving within 4 weeks; a 48 year old man on chronic zinc supplements developed fatigue and severe anemia, resolving within 2 weeks of stopping zinc intake; no mention of liver injury).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.brewer.1993.199">Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, Dick RD, Wang Y. Treatment of Wilson's disease with zinc XII: dose regimen requirements. <span><span class="ref-journal">Am J Med Sci. </span>1993;<span class="ref-vol">305</span>:199–202.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8475943" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8475943</span></a>]<div>
|
||
<i>(Analysis of copper balance in 4 patients treated with 75 mg of zinc daily in 1, 2 or 3 divided doses indicated that once daily regimen did not reliably result in a negative copper balance, suggesting that zinc must be given in divided doses 2 or 3 times daily).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.mckinney.1994.1383">McKinney PE, Brent J, Kulig K. Acute zinc chloride ingestion in a child: local and systemic effects. <span><span class="ref-journal">Ann Emerg Med. </span>1994;<span class="ref-vol">23</span>:1383–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7515217" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7515217</span></a>]<div>
|
||
<i>(16 month old boy ingested zinc chloride soldering solution and developed vomiting and lethargy with metabolic acidosis and liver test abnormalities [bilirubin normal, ALT 123 U/L, Alk P 527 U/L], resolving within 3 days, but with severe anemia lasting a week).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.brewer.1998.264">Brewer GJ, Dick RD, Johnson VD, Brunberg JA, Kluin KJ, Fink JK. Treatment of Wilson's disease with zinc: XV long-term follow-up studies. <span><span class="ref-journal">J Lab Clin Med. </span>1998;<span class="ref-vol">132</span>:264–78.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9794697" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9794697</span></a>]<div>
|
||
<i>(Description of patterns of change in urinary, hepatic and serum copper and zinc levels and liver tests in 141 patients with Wilson disease treated with zinc; adverse reactions were "minimal", the most common being initial abdominal discomfort).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.anderson.1998.78">Anderson LA, Hakojarvi SL, Boudreaux SK. Zinc acetate treatment in Wilson's disease. <span><span class="ref-journal">Ann Pharmacother. </span>1998;<span class="ref-vol">32</span>:78–87.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9475826" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9475826</span></a>]<div>
|
||
<i>(Systematic review of the literature on safety and efficacy of oral zinc therapy of Wilson disease concluded that zinc acetate was effective in maintenance of copper balance in patients with Wilson disease and has negligible toxicity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.ala.2007.397">Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson's disease. <span><span class="ref-journal">Lancet. </span>2007;<span class="ref-vol">369</span>(9559):397–408.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17276780" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17276780</span></a>]<div>
|
||
<i>(Review of the clinical features, pathogenesis, genetics, diagnosis and treatment including role of zinc).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.gurnee.2007.1174">Gurnee CM, Drobatz KJ. Zinc intoxication in dogs: 19 cases (1991-2003). <span><span class="ref-journal">J Am Vet Med Assoc. </span>2007;<span class="ref-vol">230</span>:1174–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17501656" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17501656</span></a>]<div>
|
||
<i>(Retrospective review of 19 cases of zinc toxicosis in dogs seen over an 8 year period at one veterinary hospital; dogs presented with vomiting and lethargy with pallor and jaundice, bilirubin elevations in 80% [0.5-23 mg/dL], ALT in 7% [3-92 U/L], Alk P in 92% [107-1422 U/L] and 2 deaths [10%], source of zinc being coins, tacks and bolts).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.roberts.2008.2089">Roberts EA, Schilsky ML. AASLD. Diagnosis and treatment of Wilson disease: an update. <span><span class="ref-journal">Hepatology. </span>2008;<span class="ref-vol">47</span>:2089–111.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18506894" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18506894</span></a>]<div>
|
||
<i>(Thorough review of the cause, natural history, diagnosis and treatment of Wilson disease, with specific recommendations for use of penicillamine, trientine and zinc).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.linn.2009.1442">Linn FH, Howen RH, van Hattum J, van der Kleij S, van Erpecum KJ. Long-term exclusive zinc monotherapy in symptomatic Wilson disease: experience in 17 patients. <span><span class="ref-journal">Hepatology. </span>2009;<span class="ref-vol">50</span>:1442–52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19731238" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19731238</span></a>]<div>
|
||
<i>(Among 17 Dutch patients [ages 13 to 26] with symptomatic Wilson disease treated with zinc only for 2-30 years, most had a clinical response to treatment, but 2 patients with a neurologic presentation developed liver injury after 6 and 7 years of therapy, and 2 patients with cirrhosis initially developed liver decompensation after 15 and 24 years of therapy; the efficacy of copper elimination appeared less in those with hepatic than neurologic presentations).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.walshe.2009.2289">Walshe JM. The conquest of Wilson's disease. <span><span class="ref-journal">Brain. </span>2009;<span class="ref-vol">132</span>(Pt 8):2289–95.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19596747" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19596747</span></a>]<div>
|
||
<i>(History of the initial description of Wilson disease, its link to copper accumulation, and therapies several of which were developed by the author).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.weiss.2012.1">Weiss KH, Stremmel W. Evolving perspectives in Wilson disease diagnosis: treatment and monitoring. <span><span class="ref-journal">Curr Gastroenterol Rep. </span>2012;<span class="ref-vol">14</span>:1–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22083169" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22083169</span></a>]<div>
|
||
<i>(Review of the diagnosis and management of Wilson disease, including the role of genetic testing and the choice of medical therapies).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.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>(Systematic review of literature of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, none of which was attributed to penicillamine or other agents used to treat Wilson disease).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.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, one case was attributed to penicillamine but none were attributed to zinc).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.pfeiffenberger.2018.1261">Pfeiffenberger J, Beinhardt S, Gotthardt DN, Haag N, Freissmuth C, Reuner U, Gauss A, et al. Pregnancy in Wilson's disease: management and outcome. <span><span class="ref-journal">Hepatology. </span>2018;<span class="ref-vol">67</span>:1261–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28859232" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28859232</span></a>]<div>
|
||
<i>(Among 282 pregnancies in 136 patients with Wilson disease analyzed in a retrospective, multicenter study, spontaneous abortion was less common among patients being treated with penicillamine [17%] or zinc [10%] than untreated patients [41%], which was proportionally greater than with trientine [28%] and similar to that in patients who discontinued therapy during pregnancy [36%]; worsening of liver disease arose in some patients on treatment but was self-limiting and resolved after delivery; birth defects were found in 7 of 209 [3%] newborns overall and in 4 of 98 women taking penicillamine).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.roberts.2018.56">Roberts EA. Update on the diagnosis and management of Wilson disease. <span><span class="ref-journal">Curr Gastroenterol Rep. </span>2018;<span class="ref-vol">20</span>:56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30397835" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30397835</span></a>]<div>
|
||
<i>(Review of recent advances in the understanding of the pathogenesis, clinical features, diagnosis, and treatment of Wilson disease).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Zinc.REF.appenzellerherzog.2019.2136">Appenzeller-Herzog C, Mathes T, Heeres MLS, Weiss KH, Houwen RHJ, Ewald H. Comparative effectiveness of common therapies for Wilson disease: A systematic review and meta-analysis of controlled studies. <span><span class="ref-journal">Liver Int. </span>2019;<span class="ref-vol">39</span>:2136–52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31206982" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31206982</span></a>]<div>
|
||
<i>(Systematic review of literature on therapies of Wilson disease found no differences in outcomes with penicillamine vs zinc, but higher rates of adverse events and discontinuations with penicillamine; no mention of hepatotoxicity or ALT elevations).</i>
|
||
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