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<meta name="citation_inbook_title" content="LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]">
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<meta name="citation_title" content="Foscarnet">
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<meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases">
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yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK548522_"><span class="title" itemprop="name">Foscarnet</span></h1><p class="fm-aai"><a href="#_NBK548522_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="Foscarnet.OVERVIEW"><h2 id="_Foscarnet_OVERVIEW_">OVERVIEW</h2><div id="Foscarnet.Introduction"><h3>Introduction</h3><p>Foscarnet a simple pyrophosphate molecule which has antiviral activity against many viruses and is used intravenously in therapy of serious cytomegalovirus infections, largely in immunocompromised patients. Foscarnet has been associated with mild-to-moderate serum aminotransferase elevations during intravenous therapy, but not with episodes of clinically apparent liver injury.</p></div><div id="Foscarnet.Background"><h3>Background</h3><p>Foscarnet (fos kar' net) is a pyrophosphate (phosphonoformate) that has antiviral activity against several DNA viruses, including cytomegalovirus (CMV) and hepatitis B virus. Foscarnet appears to act by inhibition of the pyrophosphate binding sites of viral DNA polymerases. Foscarnet is poorly absorbed orally and must be given intravenously. Foscarnet was approved for use in the United States in 1991, but has had limited use. Current indications include therapy of CMV retinitis and acyclovir-resistant herpes simplex infections in immunocompromised individuals. Foscarnet is available as an intravenous formulation of 24 mg/mL generically and previously under the brand name of Foscavir. The recommended dose in adults is 40 to 60 mg/kg intravenously every 8 to 12 hours for 2 to 4 weeks, which must be carefully monitored and dose adjusted for renal insufficiency. Side effects include headache, dizziness, confusion, fever, fatigue, abdominal pain, bone marrow suppression, renal dysfunction and rash. Uncommon but potentially severe adverse events include renal failure, seizures, hypersensitivity reactions, Stevens Johnson syndrome and rhabdomyolysis.</p></div><div id="Foscarnet.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>Intravenous foscarnet therapy is associated with mild-to-moderate serum ALT elevations in a proportion of patients, but the drug is usually given to patients with multiorgan disease and conditions that may be associated with some degree of hepatic injury. The ALT elevations are usually asymptomatic and resolve even with continuation of foscarnet. Single case reports of clinically apparent liver injury that were possibly attributable to foscarnet have been reported. The pattern of injury was cholestatic arising within weeks of starting foscarnet but the clinical features of the liver injury have not been described in any detail.</p><p>Likelihood score: D (possible cause of clinically apparent liver injjry).</p></div><div id="Foscarnet.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>Foscarnet is rapidly excreted in the urine and has little hepatic metabolism, which may account for its relative lack of hepatotoxicity. Acute liver injury during foscarnet therapy might be a result of a hypersensitivity reaction to the drug or of a complication of the condition for which foscarnet was used.</p></div><div id="Foscarnet.Outcome_and_Management"><h3>Outcome and Management</h3><p>The serum aminotransferase elevations during foscarnet therapy are usually self-limited and do not require dose adjustment. Foscarnet is usually given to severely immunocompromised patients who are frequently on multiple other medications, many of which may be hepatotoxic and attribution of hepatic injury in such individuals can be difficult.</p><p>Drug Class: <a href="/books/n/livertox/AntiviralAgents/?report=reader">Antiviral Agents</a></p><p>Other Antiviral Agents for Herpes Virus Infections: <a href="/books/n/livertox/Acyclovir/?report=reader">Acyclovir</a>, <a href="/books/n/livertox/Cidofovir/?report=reader">Cidofovir</a>, <a href="/books/n/livertox/Famciclovir/?report=reader">Famciclovir</a>, <a href="/books/n/livertox/GanciclovirValganc/?report=reader">Ganciclovir</a>, <a href="/books/n/livertox/Letermovir/?report=reader">Letermovir</a>, <a href="/books/n/livertox/Valacyclovir/?report=reader">Valacyclovir</a>, <a href="/books/n/livertox/GanciclovirValganc/?report=reader">Valganciclovir</a></p></div></div><div id="Foscarnet.PRODUCT_INFORMATION"><h2 id="_Foscarnet_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><div id="Foscarnet.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
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<b> REPRESENTATIVE TRADE NAMES</b>
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</p><p>Foscarnet – Generic, Foscavir®</p><p>
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<b>DRUG CLASS</b>
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</p><p>Antiviral Agents</p><p>
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<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Foscarnet" 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="Foscarnet.CHEMICAL_FORMULA_AND_STRUCTURE"><h2 id="_Foscarnet_CHEMICAL_FORMULA_AND_STRUCTURE_">CHEMICAL FORMULA AND STRUCTURE</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figFoscarnetT1"><a href="/books/NBK548522/table/Foscarnet.T1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figFoscarnetT1" rid-ob="figobFoscarnetT1"><img class="small-thumb" src="/books/NBK548522/table/Foscarnet.T1/?report=thumb" src-large="/books/NBK548522/table/Foscarnet.T1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="Foscarnet.T1"><a href="/books/NBK548522/table/Foscarnet.T1/?report=objectonly" target="object" rid-ob="figobFoscarnetT1">Table</a></h4></div></div></div><div id="Foscarnet.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Foscarnet_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 06 February 2018</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Foscarnet.R1">Zimmerman HJ. Antiviral agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 621-3.<div><i>(Expert review of antiviral agents and liver injury published in 1999; mentions that foscarnet "...has not been reported to lead to hepatic injury").</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R2">Núñez M. Hepatotoxicity of antiviral agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, p. 513.<div><i>(Review of hepatotoxicity of antiviral agents states that ALT and AST elevations occurred in 1-5% of patients treated with foscarnet in clinical trials).</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R3">Acosta EP, Flexner C. Antiviral agents (nonretroviral). In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1602-3.<div><i>(Textbook of pharmacology and therapeutics; foscarnet must be given parenterally to achieve adequate drug levels for its antiviral action; dose limiting side effects are nephrotoxicity and hypocalcemia).</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R4">Ringdén O, Lönnqvist B, Paulin T, Ahlmén J, Klintmalm G, Wahren B, Lernestedt JO. Pharmacokinetics, safety and preliminary clinical experiences using foscarnet in the treatment of cytomegalovirus infections in bone marrow and renal transplant recipients. J Antimicrob Chemother 1986; 17: 373-87. [<a href="https://pubmed.ncbi.nlm.nih.gov/3009383" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3009383</span></a>]<div><i>(Experience in 57 episodes of severe CMV infection in 46 patients given intravenous foscarnet for 2 to 46 days; elevations in serum enzymes were frequen, but usually attributed to underlying conditions; one patient developed jaundice [bilirubin 0.7 rising to 7.1 mg/dL] with mild rise in Alk P; another had tremor, hallucinations and ALT elevations with high levels of foscarnet and renal failure).</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R5">Cacoub P, Deray G, Baumelou A, Le Hoang P, Rozenbaum W, Gentilini M, Soubrie C, et al. Acute renal failure induced by foscarnet: 4 cases. Clin Nephrol 1988; 29: 315-8. [<a href="https://pubmed.ncbi.nlm.nih.gov/2840226" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2840226</span></a>]<div><i>(Four case reports of acute renal failure in patients after 5-15 days of high dose foscarnet [5-12 g/day] for CMV retinitis, improving with stopping; liver tests were either normal or not mentioned).</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R6">Palestine AG, Polis MA, De Smet MD, Baird BF, Falloon J, Kovacs JA, Davey RT, et al. A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med 1991; 115: 665-73. [<a href="https://pubmed.ncbi.nlm.nih.gov/1656826" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1656826</span></a>]<div><i>(Controlled trial of foscarnet vs delayed therapy in 24 patients with CMV retinitis and HIV infection; one patient on foscarnet and zidovudine "developed cholestatic jaundice that resolved after both drugs were withdrawn").</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R7">Chrisp P, Clissold SP. Foscarnet: a review of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with cytomegalovirus retinitis. Drugs 1991; 41: 104-29. [<a href="https://pubmed.ncbi.nlm.nih.gov/1706982" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1706982</span></a>]<div><i>(Thorough review of antiviral activity, pharmacokinetics, efficacy and safety of foscarnet; "Foscarnet has negligible effects on hepatic function, only occasionally causing slight elevations in serum transaminase levels").</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R8">Styrt B, Freiman JP. Hepatotoxicity of antiviral agents. Gastroenterol Clin North Am 1995; 24: 839-52. [<a href="https://pubmed.ncbi.nlm.nih.gov/8749901" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8749901</span></a>]<div><i>(Review of liver toxicity of antiviral agents; mentions that foscarnet has caused alterations in liver tests uncommonly [<1%]).</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R9">Drugs for non-HIV viral infections. Treat Guidel Med Lett 2007; 5: 59-70. [<a href="https://pubmed.ncbi.nlm.nih.gov/17565338" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17565338</span></a>]<div><i>(Review of status of non-antiretroviral antiviral agents for prevention and treatment of herpes, varicella-zoster, cytomegalovirus, influenza A and B, and hepatitis B and C; no mention of liver related side effects for foscarnet).</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R10">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, 8 were attributed to antiviral agents including one due to valacyclovir, but none to foscarnet). </i></div></div></li><li><div class="bk_ref" id="Foscarnet.R11">Ishiyama K, Katagiri T, Hoshino T, Yoshida T, Yamaguchi M, Nakao S. Preemptive therapy of human herpesvirus-6 encephalitis with foscarnet sodium for high-risk patients after hematopoietic SCT. Bone Marrow Transplant 2011; 46: 863-9. [<a href="https://pubmed.ncbi.nlm.nih.gov/20838386" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20838386</span></a>]<div><i>(Among 15 patients receiving hematopoietic cell transplantation, 8 received preemptive therapy with foscarnet for human herpesvirus-6 infection, among whom only 1 had liver enzyme elevations compared to 3 of 7 who did not receive foscarnet and none developed clinically apparent liver injury).</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R12">Antiviral drugs. Treat Guidel Med Lett 2013; 11 (127): 19-30. [<a href="https://pubmed.ncbi.nlm.nih.gov/23459414" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23459414</span></a>]<div><i>(Review of status of non-antiretroviral antiviral agents; foscarnet is used for acyclovir resistant varicella-zoster and herpes virus infections and for CMV retinitis in patients with AIDs; adverse effects include renal dysfunction, gastointestinal upset, CNS disturbances hypocalcemia and seizures; no mention of liver toxicity or ALT elevations).</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R13">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, 12 [1.3%] were attributed to antiviral agents, but none to foscarnet).</i></div></div></li><li><div class="bk_ref" id="Foscarnet.R14">Pierce B, Richardson CL, Lacloche L, Allen A, Ison MG. Safety and efficacy of foscarnet for the management of ganciclovir-resistant or refractory cytomegalovirus infections: a single center study. Transpl Infect Dis 2018 Jan 30. [Epub ahead of print] [<a href="https://pubmed.ncbi.nlm.nih.gov/29380479" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29380479</span></a>]<div><i>(Among 31 post-solid organ transplant patients who received foscarnet, side effects were common but related mostly to renal dysfunction; no mention of ALT elevations or hepatotoxicity and none of 10 deaths were due to liver failure).</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK548522_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">February 6, 2018</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><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>, Bethesda (MD)</p><h3>NLM Citation</h3><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Foscarnet. [Updated 2018 Feb 6].<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/livertox/AmprenavirFosampren/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/livertox/Fosfomycin/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="boxed-text" id="figobFoscarnetBPI"><div id="Foscarnet.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
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<b> REPRESENTATIVE TRADE NAMES</b>
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</p><p>Foscarnet – Generic, Foscavir®</p><p>
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<b>DRUG CLASS</b>
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</p><p>Antiviral Agents</p><p>
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<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Foscarnet" 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></article><article data-type="table-wrap" id="figobFoscarnetT1"><div id="Foscarnet.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548522/table/Foscarnet.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Foscarnet.T1_lrgtbl__"><table><thead><tr><th id="hd_h_Foscarnet.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">DRUG</th><th id="hd_h_Foscarnet.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">CAS REGISTRY NUMBER</th><th id="hd_h_Foscarnet.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Foscarnet.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_Foscarnet.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Foscarnet</td><td headers="hd_h_Foscarnet.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/134984940" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">4428-95-9</a>
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</td><td headers="hd_h_Foscarnet.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">C-H3-O5-P</td><td headers="hd_h_Foscarnet.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<div class="graphic"><img src="/books/NBK548522/bin/Foscarnet_Structure.jpg" alt="Foscarnet Chemical Structure" /></div>
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</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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