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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="#__NBK548028_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK548028_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/Siponimod/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/livertox/Sitagliptin/" 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="_NBK548028_"><span class="title" itemprop="name">Sirolimus</span></h1><p class="small">Last Update: <span itemprop="dateModified">February 17, 2020</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="Sirolimus.OVERVIEW"><h2 id="_Sirolimus_OVERVIEW_">OVERVIEW</h2><div id="Sirolimus.Introduction"><h3>Introduction</h3><p>Sirolimus is macrocyclic antibiotic with potent immunosuppressive activity that is used alone or in combination with calcineurin inhibitors and corticosteroids to prevent cellular rejection after renal transplantation. Sirolimus therapy can be associated with mild serum enzyme elevations and it has been linked to rare instances of clinically apparent cholestatic liver injury.</p></div><div id="Sirolimus.Background"><h3>Background</h3><p>Sirolimus (sir oh' li mus) is a macrocyclic lactone antibiotic which also has profound immunosuppressive properties particularly affecting T cells and the cellular immune response. Sirolimus binds to the same intracellular receptor as tacrolimus and cyclosporine, but does not inhibit calcineurin, but rather blocks the “mammalian target of rapamycin” (mTOR) which interrupts signaling pathways for several cytokines and growth factors including IL2. The result of the inhibition is inactivation of T cells. Sirolimus was approved for use in the United States in 1999 and current indications are for prevention of organ rejection after renal transplantation alone or in combination with calcineurin inhibitors or corticosteroids. It is also approved as therapy for lymphangioleiomyomatosis. Sirolimus has not been approved for use in liver or lung transplantation but is used off-label for prevention of rejection after other forms of organ transplantation after failure or intolerance to tacrolimus. Sirolimus is available as tablets of 0.5, 1 and 2 mg and in an oral solution of 1 mg/mL generically and under the brand name of Rapamune. After a loading dose, the usual maintenance dose in adults is 2 mg (~1 mg/m<sup>2</sup>) once daily. Sirolimus has less nephrotoxicity than the calcineurin inhibitors. Common side effects of sirolimus include anxiety, weakness, depression, dizziness, headache, gastrointestinal upset, oral ulcers, edema, bone marrow suppression and rash. Uncommon but potentially severe adverse events include hyperlipidemia, renal dysfunction, severe and opportunistic infections, embryo-fetal toxicity, infertility and hypersensitivity reactions. Sirolimus should be prescribed only by physicians with experience in immunosuppression and management of its complications.</p></div><div id="Sirolimus.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>Serum enzyme elevations occur in a proportion of patients taking sirolimus, but the abnormalities are usually mild, asymptomatic and self-limiting, rarely requiring dose modification or discontinuation. Rare instances of cholestatic hepatitis have been reported with sirolimus use, but the clinical features of the clinically apparent liver injury due to this agent have not been well defined. Most published cases of liver injury attributed to sirolimus occurred in patients exposed to other potentially hepatotoxic agents or who have other underlying possible causes of the abnormalities such as sepsis, cancer or parenteral nutrition. Hepatic artery thrombosis has been reported to be more common with sirolimus therapy after liver transplantation, but this association is still controversial.</p><p><a class="def" href="/books/n/livertox/glossary/def-item/glossary.likelihood-score/">Likelihood score</a>: C (probable rare cause of clinically apparent liver injury).</p></div><div id="Sirolimus.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>Sirolimus undergoes extensive hepatic metabolism, largely via the cytochrome P450 system (CYP 3A4) and drug-drug interactions are common. Sirolimus may interfere with wound healing, which has been the usual reason cited for the increased rate of hepatic artery thrombosis with its use.</p></div><div id="Sirolimus.Outcome_and_Management"><h3>Outcome and Management</h3><p>The liver injury associated with sirolimus therapy is usually mild and transient, resolving on its own or with dose modification or discontinuation. Sirolimus has not been linked to cases of acute liver failure or vanishing bile duct syndrome. There does not appear to be cross sensitivity to the hepatic injury between sirolimus and the other agents used for prevention of transplant rejection.</p><p>Agents used specifically for the prophylaxis against allograft rejection include cyclosporine, mycophenolate mofetil, sirolimus and tacrolimus, as well as azathioprine and corticosteroids.</p><p>Drug Class: <a href="/books/n/livertox/Transplant_Drugs/">Transplant Agents</a>; <a href="/books/n/livertox/AntirheumaticAgents/">Antirheumatic Agents</a>, Major Immunosuppressive Agents</p><p>Other Drugs in the Class, Transplant Agents: <a href="/books/n/livertox/Cyclosporine/">Cyclosporine</a>, <a href="/books/n/livertox/Mycophenolate/">Mycophenolate</a>, <a href="/books/n/livertox/Tacrolimus/">Tacrolimus</a></p></div></div><div id="Sirolimus.PRODUCT_INFORMATION"><h2 id="_Sirolimus_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><p>
|
||
<b>REPRESENTATIVE TRADE NAMES</b>
|
||
</p><p>Sirolimus – Generic, Rapamune®</p><p>
|
||
<b>DRUG CLASS</b>
|
||
</p><p>Transplant Agents</p><p>
|
||
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Sirolimus" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
|
||
</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div><div id="Sirolimus.CHEMICAL_FORMULA_AND_STRUCTURE"><h2 id="_Sirolimus_CHEMICAL_FORMULA_AND_STRUCTURE_">CHEMICAL FORMULA AND STRUCTURE</h2><div id="Sirolimus.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548028/table/Sirolimus.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Sirolimus.Tc_lrgtbl__"><table><tbody><tr><th id="hd_b_Sirolimus.Tc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DRUG</th><th id="hd_b_Sirolimus.Tc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CAS REGISTRY NUMBER</th><th id="hd_b_Sirolimus.Tc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_b_Sirolimus.Tc_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">STRUCTURE</th></tr><tr><td headers="hd_b_Sirolimus.Tc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sirolimus</td><td headers="hd_b_Sirolimus.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/135022432" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">53123-88-9</a>
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</td><td headers="hd_b_Sirolimus.Tc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">C51-H79-N-O13</td><td headers="hd_b_Sirolimus.Tc_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a href="https://pubchem.ncbi.nlm.nih.gov/substance/135022432" title="View this structure in PubChem" class="img_link" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem"><img src="https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?t=l&sid=135022432" alt="image 135022432 in the ncbi pubchem database" /></a>
|
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</td></tr></tbody></table></div></div></div><div id="Sirolimus.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Sirolimus_ANNOTATED_BIBLIOGRAPHY_">
|
||
<b>ANNOTATED BIBLIOGRAPHY</b>
|
||
</h2><p>References updated: 17 February 2020</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Sirolimus.REF.zimmerman.1999">Zimmerman HJ. Cyclosporine. Oncotherapeutic and immunosuppressive agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 697-8.<div><i>(Expert review of hepatotoxicity published in 1999; cyclosporine therapy was associated with a high rate of cholestatic liver enzyme elevations ranging from 4-86% and occasional instances of cholestatic hepatitis, some features of which were reproducible in animal models; tacrolimus, sirolimus, and mycophenolate are not discussed).</i></div></div></li><li><div class="bk_ref" id="Sirolimus.REF.reuben.2013">Reuben A. Hepatotoxicity of immunosuppressive drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 569-92.<div><i>(Review of hepatotoxicity of immunosuppressive agents mentions that reports of hepatotoxicity of cyclosporine have decreased since the 1980s, perhaps because of monitoring of serum levels and lower doses used; liver injury from tacrolimus, sirolimus and mycophenolate is rare and usually rapidly reversible).</i></div></div></li><li><div class="bk_ref" id="Sirolimus.REF.krensky.2018">Krensky AM, Azzi JR, Hafler DA. Immnosuppressants and tolerogens. 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. 637-54.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Sirolimus.REF.kowdley.1995.991">Kowdley KV, Keeffe EB. Hepatotoxicity of transplant immunosuppressive agents. <span><span class="ref-journal">Gastroenterol Clin North Am. </span>1995;<span class="ref-vol">24</span>:991–1001.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8749908" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8749908</span></a>]<div>
|
||
<i>(Review of reports of hepatotoxicity from cyclosporine in form of mild hyperbilirubinemia, mild-to-moderate serum enzyme elevations and biliary sludge and stones).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.kahan.2001.1903">Kahan BD. Sirolimus: a comprehensive review. <span><span class="ref-journal">Expert Opin Pharmacother. </span>2001;<span class="ref-vol">2</span>:1903–17.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11825325" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11825325</span></a>]<div>
|
||
<i>(Review of chemical structure, pharmacology, mechanism of action, clinical efficacy and safety of sirolimus; most serious adverse effects are hyperlipidemia and myelosuppression; no mention of hepatotoxicity or ALT levels).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.dunkelberg.2003.463">Dunkelberg JC, Trotter JF, Wachs M, Bak T, Kugelmas M, Steinberg T, Everson GT, et al. Sirolimus as primary immunosuppression in liver transplantation is not associated with hepatic artery or wound complications. <span><span class="ref-journal">Liver Transpl. </span>2003;<span class="ref-vol">9</span>:463–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12740787" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12740787</span></a>]<div>
|
||
<i>(Retrospective analysis of outcome of 170 patients undergoing liver transplantation and treatment with sirolimus found no increase in hepatic artery complications in comparison to historic controls).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.montalbano.2004.264">Montalbano M, Neff GW, Yamashiki N, Meyer D, Bettiol M, Slapak-Green G, Ruiz P, et al. A retrospective review of liver transplant patients treated with sirolimus from a single center: an analysis of sirolimus-related complications. <span><span class="ref-journal">Transplantation. </span>2004;<span class="ref-vol">78</span>:264–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15280688" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15280688</span></a>]<div>
|
||
<i>(Retrospective analysis of complications among 91 liver transplant recipients treated with sirolimus; common side effects were edema, oral ulcers and dermatitis; 12 developed liver test abnormalities that resolved only with stopping drug, and 2 cases of hepatic artery thrombosis).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.neff.2004.1593">Neff GW, Ruiz P, Madariaga JR, Nishida S, Montalbano M, Meyer D, Levi DM, et al. Sirolimus-associated hepatotoxicity in liver transplantation. <span><span class="ref-journal">Ann Pharmacother. </span>2004;<span class="ref-vol">38</span>:1593–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15328399" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15328399</span></a>]<div>
|
||
<i>(Among 210 liver transplant recipients who received sirolimus, 10 had evidence of hepatotoxicity but 6 had chronic hepatitis C and others rejection as primary or contributing cause).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.russo.2004.1018">Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug-induced liver injury in the United States. <span><span class="ref-journal">Liver Transpl. </span>2004;<span class="ref-vol">10</span>:1018–23.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15390328" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15390328</span></a>]<div>
|
||
<i>(Among ~50,000 liver transplants reported to UNOS between 1990 and 2002, 270 [0.5%] were done for drug induced acute liver failure, 124 for acetaminophen and 137 for other drugs or toxins, but none for agents used to prevent transplant rejection).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.niemczyk.2005.1302">Niemczyk M, Wyzga J, Perkowska A, Porowski D, Paczek L. Sirolimus-associated hepatotoxicity in the kidney graft recipient. <span><span class="ref-journal">Transpl Int. </span>2005;<span class="ref-vol">18</span>:1302–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16221163" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16221163</span></a>]<div>
|
||
<i>(30 year old man developed persistent ALT elevations 16 months after renal transplant, resolving only when sirolimus was stopped at 24 months).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.chalasani.2008.1924">Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. <span><span class="ref-journal">Gastroenterology. </span>2008;<span class="ref-vol">135</span>:1924–34.</span> [<a href="/pmc/articles/PMC3654244/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3654244</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18955056" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18955056</span></a>]<div>
|
||
<i>(Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, none were attributed to cyclosporine, tacrolimus, sirolimus or mycophenolate).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.reuben.2010.2065">Reuben A, Koch DG, Lee WM., Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. <span><span class="ref-journal">Hepatology. </span>2010;<span class="ref-vol">52</span>:2065–76.</span> [<a href="/pmc/articles/PMC3992250/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3992250</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20949552" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20949552</span></a>]<div>
|
||
<i>(Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none to an agent used to prevent transplant rejection).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.jacques.2010.967">Jacques J, Dickson Z, Carrier P, Essig M, Guillaudeau A, Lacour C, Bocquentin F, et al. Severe sirolimus-induced acute hepatitis in a renal transplant recipient. <span><span class="ref-journal">Transpl Int. </span>2010;<span class="ref-vol">23</span>:967–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20497403" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20497403</span></a>]<div>
|
||
<i>(54 year old man with renal transplant developed jaundice 2 months after switching from cyclosporine to sirolimus [bilirubin 5.4 mg/dL, ALT 609 U/L, GGT 1143 U/L], resolving within 5 weeks of switching back to cyclosporine).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.czubkowski.2012.e261">Czubkowski P, Pawłowska J, Jankowska I, Teisseyre M, Kamińska D, Markiewicz M, Ryżko J. Successful sirolimus rescue in tacrolimus-induced thrombotic microangiopathy after living-related liver transplantation. <span><span class="ref-journal">Pediatr Transplant. </span>2012;<span class="ref-vol">16</span>:E261–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22066835" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22066835</span></a>]<div>
|
||
<i>(One year old girl with biliary atresia developed tacrolimus induced microangiopathy [hemoglobin 5.6 mg/dL, indirect bilirubin 8.8 mg/dL, ALT 419 U/L, GGT 118 U/L] 8 months after living donor liver transplantation, which resolved after switching to sirolimus).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.yaich.2013.580">Yaich S, El Aoud N, Zaghdane S, Charfeddine K, Kharrat M, Masmoudi M, Hachicha J. Fatal outcome due to sirolimus-induced acute hepatitis, myelosuppression and fever in a kidney allograft recipient. <span><span class="ref-journal">Saudi J Kidney Dis Transpl. </span>2013;<span class="ref-vol">24</span>:580–2.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23640637" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23640637</span></a>]<div>
|
||
<i>(33 year old man with a renal transplant developed fever and serum enzyme elevations one month after switching from cyclosporine to sirolimus [bilirubin not given, ALT 85 U/L, Alk P 427 U/L, GGT 180], which improved on switching to tacrolimus but was followed by recurrence of fever, cough and pneumonitis and subsequent multiorgan failure and death).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.mesar.2013.1434">Mesar I, Kes P, Hudolin T, Basic-Jukic N. Rescue therapy with sirolimus in a renal transplant recipient with tacrolimus-induced hepatotoxicity. <span><span class="ref-journal">Ren Fail. </span>2013;<span class="ref-vol">35</span>:1434–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24028307" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24028307</span></a>]<div>
|
||
<i>(54 year old man with end stage renal disease developed evidence liver injury 11 days after transplant and starting tacrolimus, mycophenolate, corticosteroids and basiliximab [bilirubin 0.8 mg/dL, ALT 601 rising to 1242 U/L, GGT 144 to 212], rapidly resolving when he was switched to sirolimus).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.bj_rnsson.2013.1419">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. <span><span class="ref-journal">Gastroenterology. </span>2013;<span class="ref-vol">144</span>:1419–25.</span> [<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, none of which were attributed to an anti-rejection agent used in transplantation).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.hern_ndez.2014.231">Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A, Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America: an analysis of published reports. <span><span class="ref-journal">Ann Hepatol. </span>2014;<span class="ref-vol">13</span>:231–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24552865" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24552865</span></a>]<div>
|
||
<i>(Among 176 reports of drug induced liver injury from Latin America published between 1996 and 2012, one was attributed to mycophenolate but none to cyclosporine, sirolimus or tacrolimus).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.chalasani.2015">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, one case was attributed to cyclosporine, but none to tacrolimus, sirolimus or mycophenolate mofetil).</i></div></div></li><li><div class="bk_ref" id="Sirolimus.REF.halilo_lu.2018.279">Haliloğlu B, Tüzün H, Flanagan SE, Çelik M, Kaya A, Ellard S, Özbek MN. Sirolimus-induced hepatitis in two patients with hyperinsulinemic hypoglycemia. <span><span class="ref-journal">J Clin Res Pediatr Endocrinol. </span>2018;<span class="ref-vol">10</span>:279–83.</span> [<a href="/pmc/articles/PMC6083472/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6083472</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29217498" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29217498</span></a>]<div>
|
||
<i>(Two infants with congenital hyperinsulinemia and poorly controlled hypoglycemia developed ALT elevations [ALT 302 and 275 U/L, bilirubin and Alk P normal], 2 and 12 months after starting sirolimus which rapidly resolved after stopping sirolimus and rose again on restarting).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Sirolimus.REF.fiore.2018.3140983">Fiore M, Leone S, Maraolo AE, Berti E, Damiani G. Liver Illness and Psoriatic Patients. <span><span class="ref-journal">Biomed Res Int. </span>2018;<span class="ref-vol">2018</span>:3140983. </span> [<a href="/pmc/articles/PMC5818942/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5818942</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29546055" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29546055</span></a>]<div>
|
||
<i>(Review of liver disease in psoriasis including drug induced liver injury due to methotrexate, acitretin, TNF inhibitors, cyclosporine, and leflunomide).</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/NBK548028/?report=reader">PubReader</a></li><li><a href="/books/NBK548028/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK548028" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK548028" 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-. Sirolimus. [Updated 2020 Feb 17].<span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK548028/pdf/Bookshelf_NBK548028.pdf">PDF version of this page</a> (106K)</li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>New and Updated</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" 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="https://pubmed.ncbi.nlm.nih.gov/?term=%22LiverTox%22+AND+pmcbook&sort=date&size=200" ref="pagearea=source-links&targetsite=external&targetcat=link&targettype=uri">In PubMed</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Bulk Download</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" 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="https://ftp.ncbi.nlm.nih.gov/pub/litarch/29/31/" ref="pagearea=source-links&targetsite=external&targetcat=link&targettype=uri">Bulk download LiverTox data from FTP</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Overviews</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" 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/n/livertox/intro/">Introduction</a></li><li><a href="/books/n/livertox/ClinicalCourse/">Clinical Course</a></li><li><a href="/books/n/livertox/ClinicalOutcome/">Clinical Outcomes</a></li><li><a href="/books/n/livertox/ImmuneFeatures/">Immune Features</a></li><li><a href="/books/n/livertox/Phenotypes_intro/">Phenotypes</a></li><li><a href="/books/n/livertox/Causality/">Causality</a></li><li><a href="/books/n/livertox/DrugCategory/">Likelihood Scale</a></li><li><a href="/books/n/livertox/Severity/">Severity Grading</a></li><li><a href="/books/n/livertox/CaseReport/">Writing a Case Report</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Support Links</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" 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/n/livertox/">LiverTox Homepage</a></li><li><a href="/books/n/livertox/masterlistintro/">Master List of LiverTox Drugs [with Metadata]</a></li><li><a href="/books/n/livertox/drugliverinjury/">LiverTox Drugs by Drug Class</a></li><li><a href="/books/n/livertox/aboutus/">About LiverTox</a></li><li><a href="/books/n/livertox/editorsandreviewers/">Editors and Review Committee</a></li><li><a href="/books/n/livertox/alert/">Meetings and News</a></li><li><a href="/books/n/livertox/abbreviation/">Abbreviations Used</a></li><li><a href="/books/n/livertox/glossary/">Glossary</a></li><li><a href="/books/n/livertox/resource/">Information Resources</a></li><li><a href="/books/n/livertox/disclaimer/">User/Medical Advice Disclaimer</a></li><li><a href="/books/n/livertox/Contactus/">Contact Us</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>OTHER REFERENCE LINKS</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" 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>
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<a href="https://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pubmed&pubmedfilters=true&term=(Sirolimus/AE)+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:%222999/12/31%22%5BEDat%5D)" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri">Recent References on Sirolimus: from PubMed.gov2. </a>
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<a href="https://clinicaltrials.gov/ct2/results?term=Sirolimus" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri">Trials on Sirolimus: from ClinicalTrials.gov</a>
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href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=4868210" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/31643862" ref="ordinalpos=1&linkpos=1&log$=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> Tacrolimus.</a><span class="source">[LiverTox: Clinical and Researc...]</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> Tacrolimus.<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">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/31644062" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Cyclosporine.</a><span class="source">[LiverTox: Clinical and Researc...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Cyclosporine.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/31644164" ref="ordinalpos=1&linkpos=3&log$=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> Everolimus.</a><span class="source">[LiverTox: Clinical and Researc...]</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> Everolimus.<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">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/31643625" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Transplant Agents.</a><span class="source">[LiverTox: Clinical and Researc...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Transplant Agents.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/14526403" ref="ordinalpos=1&linkpos=5&log$=relatedarticles&logdbfrom=pubmed">Renal function improves in liver transplant recipients when switched from a calcineurin inhibitor to sirolimus.</a><span class="source">[Liver Transpl. 2003]</span><div class="brieflinkpop offscreen_noflow">Renal function improves in liver transplant recipients when switched from a calcineurin inhibitor to sirolimus.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Fairbanks KD, Eustace JA, Fine D, Thuluvath PJ. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Liver Transpl. 2003 Oct; 9(10):1079-85. </em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=31643360" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=31643360" ref="ordinalpos=1&log$=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" 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