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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="Flutamide" /><meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases" /><meta name="citation_date" content="2023/03/15" /><meta name="citation_pmid" content="31644215" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK548908/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Flutamide" /><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="2023/03/15" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK548908/" /><meta name="description" content="Flutamide is a first generation, oral nonsteroidal antiandrogen that has been used widely in the therapy of prostate cancer. Flutamide is frequently associated with minor serum aminotransferase elevations and has been linked to numerous cases of acute liver injury, which are frequently severe and can be fatal." /><meta name="og:title" content="Flutamide" /><meta name="og:type" content="book" /><meta name="og:description" content="Flutamide is a first generation, oral nonsteroidal antiandrogen that has been used widely in the therapy of prostate cancer. Flutamide is frequently associated with minor serum aminotransferase elevations and has been linked to numerous cases of acute liver injury, which are frequently severe and can be fatal." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK548908/" /><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/Flutamide/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK548908/" /><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="_NBK548908_"><span class="title" itemprop="name">Flutamide</span></h1><p class="small">Last Update: <span itemprop="dateModified">March 15, 2023</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="Flutamide.OVERVIEW"><h2 id="_Flutamide_OVERVIEW_">OVERVIEW</h2><div id="Flutamide.Introduction"><h3>Introduction</h3><p>Flutamide is a first generation, oral nonsteroidal antiandrogen that has been used widely in the therapy of prostate cancer. Flutamide is frequently associated with minor serum aminotransferase elevations and has been linked to numerous cases of acute liver injury, which are frequently severe and can be fatal.</p></div><div id="Flutamide.Background"><h3>Background</h3><p>Flutamide (floo' ta mide) is a synthetic, nonsteroidal antiandrogen that acts by competitive inhibition of the binding of testosterone and dihydrotestosterone to the intracellular androgen receptor, thus blocking the effects of endogenous androgen action. Flutamide acts by binding to and blocking intracellular androgen receptors in target tissues including not only the testes and prostate, but also skin and hair follicles. Flutamide was approved for use in therapy of prostate cancer in the United States in 1989 and has been extensively used around the world. Flutamide’s antiandrogen effects have also been applied to the therapy of hyperandrogenic states both in men and women, including acne, hirsutism and benign prostatic hypertrophy. Because of the potentially serious hepatotoxicity of flutamide, its use outside of therapy of malignant disease is no longer recommended. Newer antiandrogens with better tolerance and minimal or no risk of hepatotoxicity have been developed and largely replaced flutamide as therapy of prostatic cancer. The current indications for flutamide are limited to the treatment of prostate cancer in combination with a luteinizing hormone releasing hormone (LHRH) analog such as leuprolide or goserelin. Flutamide is available in generic forms and under the brand name of Eulexin in 125 mg capsules. The usual dose is 250 mg two to three times daily, usually in combination with other antiprostate cancer modalities such as orchiectomy or an LHRH analog. Common side effects of flutamide are rash, drowsiness, anxiety, gynecomastia and loss of libido.</p></div><div id="Flutamide.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>Chronic therapy with flutamide is associated with elevations in serum aminotransferase levels in up to 62% of patients, but marked elevations (above 5 times ULN) in only 3% to 5%. Most of these abnormalities are transient, asymptomatic and do not require dose adjustment or drug discontinuation. However, in 0.1% to 1% of patients, acute liver injury with symptoms and jaundice arises which can be prolonged, severe and even fatal. The latency of onset ranges widely from 1 to 10 months (Cases 2 and 3), averaging 3 months. Allergic manifestations are rare as are autoantibodies. The pattern of liver enzyme elevations is most commonly hepatocellular, but many cases with cholestatic and mixed patterns have been described. Liver failure with a requirement for emergency liver transplantation or fatality has been described in many publications with 20 fatal cases reported from the FDA MedWatch program during the first 5 years of its availability. Fatal cases have been reported in children and young women being treated for hirsutism or acne (Case 1).</p><p>Current recommendations for routine monitoring of liver tests include ALT levels monthly for the first 4 months of flutamide therapy and regularly thereafter with prompt discontinuation if ALT levels rise above twice ULN. Nevertheless, well characterized fatal cases have occurred despite such monitoring, the onset of injury being abrupt and injury continuing for several weeks after discontinuation of flutamide. The injury may be partially dose related as long term use of lower doses of flutamide (62.5 and 125 mg/day) has not been associated with high rates of ALT elevations or clinically apparent liver injury.</p><p>Likelihood score: A (well known cause of clinically apparent liver injury).</p></div><div id="Flutamide.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>The mechanism of injury due to flutamide is not clearly understood. Flutamide is extensively metabolized by the liver, and a common hypothesis is that flutamide is metabolized by the cytochrome P450 system (CYP 3A4) to a toxic intermediate.</p></div><div id="Flutamide.Outcome_and_Management"><h3>Outcome and Management</h3><p>The mortality rate of flutamide hepatotoxicity is considerable, particularly in cases with a hepatocellular pattern of injury and in elderly men. Generally, the injury begins to resolve within 1 to 2 weeks of stopping therapy. In severe cases, there can be progressive worsening with development of hypoalbuminemia, edema, ascites, hepatic encephalopathy and coagulopathy. Some patients with acute liver failure due to flutamide have undergone successful liver transplantation, but the underlying diagnosis of prostate cancer usually excludes patients from consideration for transplantation. Chronic injury from flutamide has not been described, but long term follow up on patients with flutamide injury is rarely available. Rechallenge with flutamide generally causes recurrence of injury and should be avoided. Switching therapy to other androgens (bicalutamide or nilutamide) has not been reported, but several instances of recurrence of hepatic injury have been reported among patients switched from flutamide to cyproterone acetate. Because of its known hepatotoxicity, flutamide is used less frequently than in the past. Patients on flutamide should be monitored for liver test abnormalities on a regular basis, at least during the first 4 months of treatment.</p><p>Drug Class: <a href="/books/n/livertox/AntineoplasticAgents/">Antineoplastic Agents</a>, <a href="/books/n/livertox/Anti-androgens/">Antiandrogens</a></p></div></div><div id="Flutamide.CASE_REPORTS"><h2 id="_Flutamide_CASE_REPORTS_">CASE REPORTS</h2><div id="Flutamide.Case_1_Liver_failure_in_a_14_y"><h3>Case 1. Liver failure in a 14 year old hirsute female following flutamide therapy.(<a class="bk_pop" href="#Flutamide.REF.1">1</a>)</h3><p>A 14 year old girl was treated with flutamide (250 mg twice daily) for hirsutism and presented with a 2 week history of weakness, poor appetite and dark urine 3 months later. Her past medical history was unremarkable. She had no known risk factors for viral hepatitis and was not taking other drugs or herbal medicines. On admission, she was jaundiced but not febrile and was fully alert without asterixis. Laboratory results showed total bilirubin of 7.3 mg/dL and marked elevations in serum aminotransferase levels (ALT 2372 U/L, AST 1707 U/L) and decrease in prothrombin index (29%). Tests for hepatitis A, B and C were negative as were autoantibodies. Abdominal ultrasound was normal. Over the next few days, serum bilirubin levels rose to 17.5 mg/dL and she developed signs of hepatic encephalopathy. Because of a worsening clinical condition, she was transferred to a liver transplantation center and received a deceased donor liver graft 9 days later. The explanted liver showed massive necrosis. The liver transplantation was successful and she was discharged two months later.</p><div id="Flutamide.Key_Points"><h4>Key Points</h4><div id="Flutamide.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548908/table/Flutamide.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Flutamide.Tc_lrgtbl__"><table><tbody><tr><th id="hd_b_Flutamide.Tc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Medication:</th><td headers="hd_b_Flutamide.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Flutamide (250 mg twice daily)</td></tr><tr><th id="hd_b_Flutamide.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pattern:</th><td headers="hd_b_Flutamide.Tc_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hepatocellular</td></tr><tr><th id="hd_b_Flutamide.Tc_1_1_3_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Severity:</th><td headers="hd_b_Flutamide.Tc_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5+ (liver transplantation)</td></tr><tr><th id="hd_b_Flutamide.Tc_1_1_4_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Latency:</th><td headers="hd_b_Flutamide.Tc_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">~3 months</td></tr><tr><th id="hd_b_Flutamide.Tc_1_1_5_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Recovery:</th><td headers="hd_b_Flutamide.Tc_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Required liver transplantation</td></tr><tr><th id="hd_b_Flutamide.Tc_1_1_6_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other medications:</th><td headers="hd_b_Flutamide.Tc_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">None</td></tr></tbody></table></div></div></div><div id="Flutamide.Comment"><h4>Comment</h4><p>There have been many case reports of acute liver failure attributable to flutamide therapy, but largely in elderly men being treated for metastatic prostate cancer. This case report and several like it demonstrate that acute liver failure from flutamide can occur in women as well as men, and in children and young adults as well as in the elderly. For this reason, this agent should be reserved for persons with medically severe or malignant conditions. The typical onset of flutamide associated liver injury is the abrupt appearance of jaundice after 2 to 3 months of therapy. Signs of hypersensitivity and autoimmunity are rare and serum enzymes usually demonstrate a markedly hepatocellular pattern. While the injury is rapidly reversible, the degree of injury may be such that hepatic failure occurs rapidly and is not reversible. Recently, studies of low and “ultra-low” doses of flutamide (62.5 to 250 mg daily) as therapy of hirsutism have been reported showing little or no evidence of hepatic injury (based upon ALT testing) during therapy for 12 months and longer. Nevertheless, the therapeutic window is narrow and neither flutamide or the other synthetic antiandrogens are approved for use in benign hyperandrogenic conditions in the United States.</p></div></div><div id="Flutamide.Case_2_Hepatitis_and_jaundice"><h3>Case 2. Hepatitis and jaundice after flutamide therapy of prostate cancer.(<a class="bk_pop" href="#Flutamide.REF.2">2</a>)</h3><p>A 65 year old man with prostate cancer underwent bilateral orchidectomy and was started on flutamide (250 mg twice daily). Eight months later, he developed nausea and subsequently noted fatigue and jaundice. He was hospitalized and found to have fever, jaundice and hepatic tenderness. He had no previous history of liver disease and no risk factors for hepatitis or alcohol use. His other medical conditions included diabetes, coronary artery disease and hyperlipidemia. Laboratory tests showed a bilirubin of 24 mg/dL and marked elevations in serum aminotransferase levels with minimal increase in alkaline phosphatase (Table). Tests for hepatitis A, B, C, and E were negative as were autoantibodies. Liver imaging showed no evidence of obstruction. A liver biopsy showed intrahepatic cholestasis with mild inflammatory changes and no fibrosis, compatible with drug induced liver disease. Flutamide was stopped and he was treated with antibiotics and ursodiol. He improved slowly and remained jaundiced for several months. A one month course of corticosteroids was given with marked improvement in symptoms and jaundice. Four months after onset of illness he was off of corticosteroids and ursodiol and his liver tests had returned to normal.</p><div id="Flutamide.Key_Points_1"><h4>Key Points</h4><div id="Flutamide.Td" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548908/table/Flutamide.Td/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Flutamide.Td_lrgtbl__"><table><tbody><tr><th id="hd_b_Flutamide.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Medication:</th><td headers="hd_b_Flutamide.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Flutamide (250 mg twice daily)</td></tr><tr><th id="hd_b_Flutamide.Td_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pattern:</th><td headers="hd_b_Flutamide.Td_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hepatocellular</td></tr><tr><th id="hd_b_Flutamide.Td_1_1_3_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Severity:</th><td headers="hd_b_Flutamide.Td_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4+ (jaundice, hospitalization and rise in INR above 1.5)</td></tr><tr><th id="hd_b_Flutamide.Td_1_1_4_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Latency:</th><td headers="hd_b_Flutamide.Td_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8 months (onset of nausea)</td></tr><tr><th id="hd_b_Flutamide.Td_1_1_5_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Recovery:</th><td headers="hd_b_Flutamide.Td_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4 months</td></tr><tr><th id="hd_b_Flutamide.Td_1_1_6_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other medications:</th><td headers="hd_b_Flutamide.Td_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Metformin, isosorbide mononitrate, amlodipine, simvastatin</td></tr></tbody></table></div></div></div><div id="Flutamide.Laboratory_Values"><h4>Laboratory Values</h4><div id="Flutamide.Te" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548908/table/Flutamide.Te/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Flutamide.Te_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_Flutamide.Te_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Time After<br /><b>Starting</b></th><th id="hd_h_Flutamide.Te_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Time After<br /><b>Stopping</b></th><th id="hd_h_Flutamide.Te_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">ALT<br /><b>(U/L)</b></th><th id="hd_h_Flutamide.Te_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Alk P<br /><b>(U/L)</b></th><th id="hd_h_Flutamide.Te_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Bilirubin<br /><b>(mg/dL)</b></th><th id="hd_h_Flutamide.Te_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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Other
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</th></tr></thead><tbody><tr><td headers="hd_h_Flutamide.Te_1_1_1_1 hd_h_Flutamide.Te_1_1_1_2 hd_h_Flutamide.Te_1_1_1_3 hd_h_Flutamide.Te_1_1_1_4 hd_h_Flutamide.Te_1_1_1_5 hd_h_Flutamide.Te_1_1_1_6" colspan="6" scope="col" rowspan="1" style="text-align:left;vertical-align:top;">Flutamide 250 mg twice daily started for prostate cancer</td></tr><tr><td headers="hd_h_Flutamide.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9 months</td><td headers="hd_h_Flutamide.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_Flutamide.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">646</td><td headers="hd_h_Flutamide.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">114*</td><td headers="hd_h_Flutamide.Te_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">24.0</td><td headers="hd_h_Flutamide.Te_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Albumin 4.3 g/dL</td></tr><tr><td headers="hd_h_Flutamide.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1 week</td><td headers="hd_h_Flutamide.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">348</td><td headers="hd_h_Flutamide.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Te_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">29.0</td><td headers="hd_h_Flutamide.Te_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Flutamide.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2 weeks</td><td headers="hd_h_Flutamide.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">242</td><td headers="hd_h_Flutamide.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">146</td><td headers="hd_h_Flutamide.Te_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">33.5</td><td headers="hd_h_Flutamide.Te_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Flutamide.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3 weeks</td><td headers="hd_h_Flutamide.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">182</td><td headers="hd_h_Flutamide.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">138</td><td headers="hd_h_Flutamide.Te_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">19.6</td><td headers="hd_h_Flutamide.Te_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Flutamide.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10 months</td><td headers="hd_h_Flutamide.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4 weeks</td><td headers="hd_h_Flutamide.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">104</td><td headers="hd_h_Flutamide.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">108</td><td headers="hd_h_Flutamide.Te_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">13.7</td><td headers="hd_h_Flutamide.Te_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Protime 16 sec</td></tr><tr><td headers="hd_h_Flutamide.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5 weeks</td><td headers="hd_h_Flutamide.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">68</td><td headers="hd_h_Flutamide.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">150</td><td headers="hd_h_Flutamide.Te_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11.3</td><td headers="hd_h_Flutamide.Te_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Corticosteroids started</td></tr><tr><td headers="hd_h_Flutamide.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6 weeks</td><td headers="hd_h_Flutamide.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">69</td><td headers="hd_h_Flutamide.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">158*</td><td headers="hd_h_Flutamide.Te_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11.5</td><td headers="hd_h_Flutamide.Te_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Flutamide.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11 months</td><td headers="hd_h_Flutamide.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8 weeks</td><td headers="hd_h_Flutamide.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">66</td><td headers="hd_h_Flutamide.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Te_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.5</td><td headers="hd_h_Flutamide.Te_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Corticosteroids stopped</td></tr><tr><td headers="hd_h_Flutamide.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12 months</td><td headers="hd_h_Flutamide.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">14 weeks</td><td headers="hd_h_Flutamide.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">18</td><td headers="hd_h_Flutamide.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">76</td><td headers="hd_h_Flutamide.Te_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.5</td><td headers="hd_h_Flutamide.Te_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Asymptomatic</td></tr><tr><td headers="hd_h_Flutamide.Te_1_1_1_1 hd_h_Flutamide.Te_1_1_1_2" colspan="2" scope="row" rowspan="1" style="text-align:center;vertical-align:top;">
|
||
<b>Normal Values</b>
|
||
</td><td headers="hd_h_Flutamide.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
||
<b><40</b>
|
||
</td><td headers="hd_h_Flutamide.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
||
<b><120</b>
|
||
</td><td headers="hd_h_Flutamide.Te_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
||
<b><1.2</b>
|
||
</td><td headers="hd_h_Flutamide.Te_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>*</dt><dd><div id="Flutamide.TF.e.1"><p class="no_margin">Values adjusted to standard upper limit of normal.</p></div></dd></dl></div></div></div></div><div id="Flutamide.Comment_1"><h4>Comment</h4><p>A case of prolonged flutamide associated hepatitis arising after 9 months of therapy. The serum enzyme pattern of a 20-fold elevation in aminotransferase levels with minimal increase in alkaline phosphatase defines the case as “hepatocellular”, but the clinical course of the illness was decidedly cholestatic with severe jaundice and pruritus. While corticosteroids have not been proven to be beneficial in acute drug induced liver injury, they may alleviate symptoms and decrease bilirubin in some patients with prolonged cholestasis, as in this case. Importantly, the dose of corticosteroids was reduced rapidly and they were stopped within a month or two. The authors hypothesized that simvastatin may have added to the liver injury; but flutamide by itself has been clearly implicated in many instances of hepatotoxicity of similar severity. Regardless, in patients presenting with jaundice of unknown cause, it is prudent to withdraw all but the most necessary medications until recovery.</p></div></div><div id="Flutamide.Case_3_Acute_hepatitis_due_to"><h3>Case 3. Acute hepatitis due to flutamide therapy.(<a class="bk_pop" href="#Flutamide.REF.3">3</a>)</h3><p>A 66 year old man with advanced prostate cancer developed jaundice 4 weeks after starting antiandrogen therapy with flutamide. He had a past medical history of essential hypertension and type 2 diabetes for which he had been taking candesartan (16 mg daily) and glyburide (3.5 mg daily) for several years. Prostate cancer was diagnosed by biopsy and was treated with hormonal ablation using flutamide (750 mg daily) and monthly injections of the LHRH analog goserelin. On admission, he was deeply jaundiced but had no rash, fever, or signs of hepatic decompensation. Laboratory testing showed serum bilirubin of 13.6 mg/dL, ALT 2160 U/L and alkaline phosphatase 900 U/L (Table). Tests for hepatitis A, B and C and for EBV infection were negative as were autoantibodies. Ultrasound of the abdomen showed no hepatic masses and no evidence of bile duct dilation. A liver biopsy showed intrahepatic cholestasis suggestive of drug induced liver injury. Flutamide was stopped on admission and he started to improve rapidly. In follow up 2 months later, all laboratory tests were normal. He was continued on therapy with goserelin.</p><div id="Flutamide.Key_Points_2"><h4>Key Points</h4><div id="Flutamide.Tf" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548908/table/Flutamide.Tf/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Flutamide.Tf_lrgtbl__"><table><tbody><tr><th id="hd_b_Flutamide.Tf_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Medication:</th><td headers="hd_b_Flutamide.Tf_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Flutamide (250 mg twice daily)</td></tr><tr><th id="hd_b_Flutamide.Tf_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pattern:</th><td headers="hd_b_Flutamide.Tf_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hepatocellular (R=16)</td></tr><tr><th id="hd_b_Flutamide.Tf_1_1_3_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Severity:</th><td headers="hd_b_Flutamide.Tf_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3+ (jaundice and hospitalization)</td></tr><tr><th id="hd_b_Flutamide.Tf_1_1_4_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Latency:</th><td headers="hd_b_Flutamide.Tf_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">One month (to onset of jaundice)</td></tr><tr><th id="hd_b_Flutamide.Tf_1_1_5_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Recovery:</th><td headers="hd_b_Flutamide.Tf_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">One month</td></tr><tr><th id="hd_b_Flutamide.Tf_1_1_6_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other medications:</th><td headers="hd_b_Flutamide.Tf_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Candesartan and glyburide chronically; goserelin for 4 weeks</td></tr></tbody></table></div></div></div><div id="Flutamide.Laboratory_Values_1"><h4>Laboratory Values</h4><div id="Flutamide.Tg" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548908/table/Flutamide.Tg/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Flutamide.Tg_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_Flutamide.Tg_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Time After<br />Starting</th><th id="hd_h_Flutamide.Tg_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Time After<br />Stopping</th><th id="hd_h_Flutamide.Tg_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">ALT*<br />(U/L)</th><th id="hd_h_Flutamide.Tg_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Alk P*<br />(U/L)</th><th id="hd_h_Flutamide.Tg_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Bilirubin<br />(mg/dL)</th><th id="hd_h_Flutamide.Tg_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Other</th></tr></thead><tbody><tr><td headers="hd_h_Flutamide.Tg_1_1_1_1 hd_h_Flutamide.Tg_1_1_1_2 hd_h_Flutamide.Tg_1_1_1_3 hd_h_Flutamide.Tg_1_1_1_4 hd_h_Flutamide.Tg_1_1_1_5 hd_h_Flutamide.Tg_1_1_1_6" colspan="6" scope="col" rowspan="1" style="text-align:center;vertical-align:top;">Flutamide 250 mg three times daily started for prostate cancer</td></tr><tr><td headers="hd_h_Flutamide.Tg_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4 weeks</td><td headers="hd_h_Flutamide.Tg_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_Flutamide.Tg_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2160</td><td headers="hd_h_Flutamide.Tg_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">900</td><td headers="hd_h_Flutamide.Tg_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">13.6</td><td headers="hd_h_Flutamide.Tg_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">INR 81%, albumin 3.9</td></tr><tr><td headers="hd_h_Flutamide.Tg_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Tg_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2 days</td><td headers="hd_h_Flutamide.Tg_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1825</td><td headers="hd_h_Flutamide.Tg_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">763</td><td headers="hd_h_Flutamide.Tg_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9.4</td><td headers="hd_h_Flutamide.Tg_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Liver biopsy</td></tr><tr><td headers="hd_h_Flutamide.Tg_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Tg_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5 days</td><td headers="hd_h_Flutamide.Tg_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1470</td><td headers="hd_h_Flutamide.Tg_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">540</td><td headers="hd_h_Flutamide.Tg_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.4</td><td headers="hd_h_Flutamide.Tg_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Prednisone for ~2 weeks</td></tr><tr><td headers="hd_h_Flutamide.Tg_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5 weeks</td><td headers="hd_h_Flutamide.Tg_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7 days</td><td headers="hd_h_Flutamide.Tg_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">750</td><td headers="hd_h_Flutamide.Tg_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">450</td><td headers="hd_h_Flutamide.Tg_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.2</td><td headers="hd_h_Flutamide.Tg_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Flutamide.Tg_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Tg_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9 days</td><td headers="hd_h_Flutamide.Tg_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">600</td><td headers="hd_h_Flutamide.Tg_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">420</td><td headers="hd_h_Flutamide.Tg_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.6</td><td headers="hd_h_Flutamide.Tg_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Flutamide.Tg_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Flutamide.Tg_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12 days</td><td headers="hd_h_Flutamide.Tg_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">360</td><td headers="hd_h_Flutamide.Tg_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">330</td><td headers="hd_h_Flutamide.Tg_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.5</td><td headers="hd_h_Flutamide.Tg_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Flutamide.Tg_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6 weeks</td><td headers="hd_h_Flutamide.Tg_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2 weeks</td><td headers="hd_h_Flutamide.Tg_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">270</td><td headers="hd_h_Flutamide.Tg_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">288</td><td headers="hd_h_Flutamide.Tg_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.2</td><td headers="hd_h_Flutamide.Tg_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Flutamide.Tg_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7 weeks</td><td headers="hd_h_Flutamide.Tg_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3 weeks</td><td headers="hd_h_Flutamide.Tg_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">40</td><td headers="hd_h_Flutamide.Tg_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">240</td><td headers="hd_h_Flutamide.Tg_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.8</td><td headers="hd_h_Flutamide.Tg_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Flutamide.Tg_1_1_1_1 hd_h_Flutamide.Tg_1_1_1_2" colspan="2" scope="row" rowspan="1" style="text-align:center;vertical-align:top;">
|
||
<b>Normal Values</b>
|
||
</td><td headers="hd_h_Flutamide.Tg_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
||
<b><40</b>
|
||
</td><td headers="hd_h_Flutamide.Tg_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
||
<b><270</b>
|
||
</td><td headers="hd_h_Flutamide.Tg_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
||
<b><1.2</b>
|
||
</td><td headers="hd_h_Flutamide.Tg_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>*</dt><dd><div id="Flutamide.TF.g.1"><p class="no_margin">Values estimated from figure and bilirubin converted from µmol to mg/dL.</p></div></dd></dl></div></div></div></div><div id="Flutamide.Comment_2"><h4>Comment</h4><p>Although the latency to onset of one month was somewhat short (the usual latency being 2-6 months), this case was otherwise quite typical with a hepatocellular pattern of serum enzyme elevations and rapid improvement with stopping therapy. Cases with a fulminant course usually show evidence of hepatic failure even on presentation, with prolonged prothrombin time accompanying the marked aminotransferase elevations.</p></div></div></div><div id="Flutamide.PRODUCT_INFORMATION"><h2 id="_Flutamide_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><p>
|
||
<b>REPRESENTATIVE TRADE NAMES</b>
|
||
</p><p>Flutamide – Generic, Eulexin®</p><p>
|
||
<b>DRUG CLASS</b>
|
||
</p><p>Antineoplastic Agents</p><p>
|
||
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=flutamide" 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="Flutamide.CHEMICAL_FORMULA_AND_STRUCTURE"><h2 id="_Flutamide_CHEMICAL_FORMULA_AND_STRUCTURE_">CHEMICAL FORMULA AND STRUCTURE</h2><div id="Flutamide.Th" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548908/table/Flutamide.Th/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Flutamide.Th_lrgtbl__"><table><thead><tr><th id="hd_h_Flutamide.Th_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DRUG</th><th id="hd_h_Flutamide.Th_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_Flutamide.Th_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Flutamide.Th_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_Flutamide.Th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Flutamide</td><td headers="hd_h_Flutamide.Th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/134990691" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">13311-84-7</a>
|
||
</td><td headers="hd_h_Flutamide.Th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">C11-H11-F3-N2-O3</td><td headers="hd_h_Flutamide.Th_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/134990691" 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=134990691" alt="image 134990691 in the ncbi pubchem database" /></a>
|
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</td></tr></tbody></table></div></div></div><div id="Flutamide.CITED_REFERENCES"><h2 id="_Flutamide_CITED_REFERENCES_">CITED REFERENCES</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="Flutamide.REF.1">Andrade RJ, Lucena MI, Fernández MC, Suarez F, Montero JL, Fraga E, Hidalgo F. Fulminant liver failure associated with flutamide therapy for hirsutism. <span><span class="ref-journal">Lancet. </span>1999;<span class="ref-vol">353</span>:983.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10459914" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10459914</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="Flutamide.REF.2">Ashar U, Desai D, Bhaduri A. Flutamide-induced hepatotoxicity with possible potentiation by simvastatin. <span><span class="ref-journal">J Assoc Physicians India. </span>2003;<span class="ref-vol">51</span>:75–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12693464" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12693464</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="Flutamide.REF.3">Lübbert C, Wiese M, Haupt R, Ruf BR. <span><span class="ref-journal">Internist (Berl). </span>2004;<span class="ref-vol">45</span>:333–40.</span> [Toxic hepatitis and liver failure under therapy with flutamide] German. [<a href="https://pubmed.ncbi.nlm.nih.gov/14997310" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14997310</span></a>]</div></dd></dl></div><div id="Flutamide.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Flutamide_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 15 March 2023</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Flutamide.REF.zimmerman.1999">Zimmerman HJ. Hepatotoxic effects of oncotherapeutic and immunosuppressive agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, p. 699.<div><i>(Expert review of hepatotoxicity published in 1999, mentions that flutamide has led to instances of severe hepatic necrosis and fulminant hepatic failure).</i></div></div></li><li><div class="bk_ref" id="Flutamide.REF.deleve.2013">DeLeve LD. Flutamide. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd Edition. Amsterdam: Elsevier. 2013. pp. 559.<div><i>(Textbook on drug induced liver injury mentions that flutamide has been implicate in at least 46 cases of severe liver injury with 20 fatalities).</i></div></div></li><li><div class="bk_ref" id="Flutamide.REF.moy.2011">Moy B, Lee RJ, Smith M. Hormone therapy in prostate cancer. Natural products in cancer chemotherapy: hormones and related agents. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1763-9.<div><i>(Textbook of pharmacology and therapeutics; discusses the role of androgen receptor blockers in prostate cancer including bicalutamide, flutamide and nilutamide).</i></div></div></li><li><div class="bk_ref" id="Flutamide.REF.lund.1988.140">Lund F, Rasmussen F. Flutamide versus stilboestrol in the management of advanced prostatic cancer. A controlled prospective study. <span><span class="ref-journal">Br J Urol. </span>1988;<span class="ref-vol">61</span>:140–2.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3280080" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3280080</span></a>]<div>
|
||
<i>(In a prospective study comparing flutamide to DES, one of 20 flutamide treated patients developed "massive jaundice" within 1 month of starting [bilirubin and ALT not given, Alk P 3950 U/L], resolving within 2 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.hart.1989.943">Hart W, Stricker BH. Flutamide and hepatitis. <span><span class="ref-journal">Ann Intern Med. </span>1989;<span class="ref-vol">110</span>:943–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2719431" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2719431</span></a>]<div>
|
||
<i>(70 year old man with prostate cancer developed jaundice after 5 weeks of flutamide therapy [bilirubin 4.3 mg/dL, ALT 158 U/L, Alk P 1070 U/L], resolving within 3 weeks of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.m_ller.1989.173">Møller S, Iversen P. <span><span class="ref-journal">Ugeskr Laeger. </span>1989;<span class="ref-vol">151</span>:173–4.</span> [Severe toxic hepatitis during flutamide (Eulexin) treatment] Danish. [<a href="https://pubmed.ncbi.nlm.nih.gov/2911917" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2911917</span></a>]<div>
|
||
<i>(Danish publication of cases later published in J Hepatol [Møller 1990] in English).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.copp_r_.1990.105">Coppéré H, Perraud Y, Gérard F, Jouffre C, David A, Barthélémy C, Audigier JC. <span><span class="ref-journal">Gastroenterol Clin Biol. </span>1990;<span class="ref-vol">14</span>:105–6.</span> [A case of acute hepatitis caused by flutamide] French. [<a href="https://pubmed.ncbi.nlm.nih.gov/2311846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2311846</span></a>]<div>
|
||
<i>(54 year old man with prostate cancer developed weakness after 6 months of flutamide therapy [bilirubin normal, ALT 4.2 times ULN, Alk P normal], levels returning to normal after stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.m_ller.1990.346">Møller S, Iversen P, Franzmann MB. Flutamide-induced liver failure. <span><span class="ref-journal">J Hepatol. </span>1990;<span class="ref-vol">10</span>:346–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2365984" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2365984</span></a>]<div>
|
||
<i>(2 men, ages 60 and 69 years, with prostate cancer developed jaundice 15 and 2 weeks after starting flutamide [bilirubin 34.6 and 14.9 mg/dL, AST 778 and 56 U/L, Alk P 401 and 1202 U/L], one case with coma; both recovered within 2-3 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.pavonemacaluso.1990.328">Pavone-Macaluso M, Cacciatore M, Daricello G, Pavone C, Serretta V. Carcinoma of the prostate. Guidelines for treatment: the role of antiandrogens. <span><span class="ref-journal">Ann N Y Acad Sci. </span>1990;<span class="ref-vol">595</span>:328–33.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2375611" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2375611</span></a>]<div>
|
||
<i>(In an early experience with using flutamide and cyproterone in 22 patients, one required drug discontinuation because of “liver insufficiency” and ALT elevations).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.alperine.1991.1459">Alperine M, Cohen L, Cocheton JJ, Lecomte I, Meyniel D. <span><span class="ref-journal">Presse Med. </span>1991;<span class="ref-vol">20</span>:1459–60.</span> [Acute hepatitis caused by flutamide] French. [<a href="https://pubmed.ncbi.nlm.nih.gov/1835038" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1835038</span></a>]<div>
|
||
<i>(65 year old man with prostate cancer developed jaundice 3 months after starting flutamide [bilirubin 9.6 mg/dL, ALT 10 times and Alk P 2 times ULN], developing ascites but improving rapidly once flutamide was stopped, with full recovery within 2 months).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.corkery.1991.364">Corkery JC, Bihrle W 3rd, McCaffrey JA, Whitcomb FF, Levy C, Ellis R. Flutamide-related fulminant hepatic failure. <span><span class="ref-journal">J Clin Gastroenterol. </span>1991;<span class="ref-vol">13</span>:364–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2066558" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2066558</span></a>]<div>
|
||
<i>(59 year old man with prostate cancer developed jaundice 6 months after starting flutamide [bilirubin 28 mg/dL, AST 1887 U/L, Alk P 312 U/L], subsequently dying of progressive liver failure).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.dankoff.1992.1914">Dankoff JS. Near fatal liver dysfunction secondary to administration of flutamide for prostate cancer. <span><span class="ref-journal">J Urol. </span>1992;<span class="ref-vol">148</span>:1914.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1433640" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1433640</span></a>]<div>
|
||
<i>(66 year old man with prostate cancer developed jaundice 10 weeks after starting flutamide [bilirubin 17.4 mg/dL, ALT 1323 U/L], resolving 6 weeks after stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.gomez.1992.465">Gomez JL, Dupont A, Cusan L, Tremblay M, Suburu R, Lemay M, Labrie F. Incidence of liver toxicity associated with the use of flutamide in prostate cancer patients. <span><span class="ref-journal">Am J Med. </span>1992;<span class="ref-vol">92</span>:465–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1349790" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1349790</span></a>]<div>
|
||
<i>(Prospective study of 1091 patients with prostate cancer given flutamide, routine ALT monitoring found 4 [0.36%] patients with ALT >4 times ULN, one with jaundice [bilirubin 7.4 mg/dL, ALT 209 U/L, Alk P 640 U/L], all recovering after stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.mart_nez_bruna.1993.566">Martínez Bruna MS, Velila Alcubilla JP, Abinzano M, Martínez Velasco C, García Mauriz ME, Urbieta Echezareta M. <span><span class="ref-journal">An Med Interna. </span>1993;<span class="ref-vol">10</span>:566.</span> [Hepatotoxicity and flutamide] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/8117876" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8117876</span></a>]<div>
|
||
<i>(79 year old man with prostate cancer developed jaundice [bilirubin 3.2 mg/dL] within a month of starting flutamide with normal ALT, AST and Alk P and fall of bilirubin to normal within 4 weeks).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.rosman.1993.1756">Rosman AS, Frissora-Rodeo C, Marshall AT, Reiter BP, Paronetto F. Cholestatic hepatitis following flutamide. <span><span class="ref-journal">Dig Dis Sci. </span>1993;<span class="ref-vol">38</span>:1756–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8359091" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8359091</span></a>]<div>
|
||
<i>(72 year old man with prostate cancer developed jaundice 3 months after starting flutamide [bilirubin 13.0 mg/dL, ALT 443 U/L, Alk P 3054 U/L], resolving within 6 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.wallace.1993.1150">Wallace C, Lalor EA, Chik CL. Hepatotoxicity complicating flutamide treatment of hirsutism. <span><span class="ref-journal">Ann Intern Med. </span>1993;<span class="ref-vol">119</span>:1150.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8110241" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8110241</span></a>]<div>
|
||
<i>(20 year old woman developed jaundice and severe pruritus 6 weeks after starting flutamide for acne [bilirubin 15.3 rising to 28.0 mg/dL, ALT 1481 U/L, Alk P 180 U/L], resolving within 3 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.wysowski.1993.860">Wysowski DK, Freiman JP, Tourtelot JB, Horton ML 3rd. Fatal and nonfatal hepatotoxicity associated with flutamide. <span><span class="ref-journal">Ann Intern Med. </span>1993;<span class="ref-vol">118</span>:860–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7683180" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7683180</span></a>]<div>
|
||
<i>(Description of 19 cases of flutamide hepatotoxicity reported to FDA between 1989-91, mean latency 56 days, 16 had hyperbilirubinemia, 5 deaths; 2 detailed case reports of men with prostate cancer developing jaundice 2 and 3 months after starting flutamide and LHRH analog [bilirubin peak of 35.4 and 2.1 mg/dL, ALT 1841 and 1871 U/L]; one case fatal).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.caballer_a.1994.434">Caballería E, Aragó JV, Sanchís A. <span><span class="ref-journal">Med Clin (Barc). </span>1994;<span class="ref-vol">102</span>:434.</span> [Hepatotoxicity due to flutamide] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/8183002" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8183002</span></a>]<div>
|
||
<i>(78 year old man with prostate cancer developed symptoms and jaundice 1 month after starting flutamide [bilirubin 1.2 rising to 6.5 mg/dL, ALT 716 U/L, Alk P 203 U/L], rapid resolution upon stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.dourakis.1994.350">Dourakis SP, Alexopoulou AA, Hadziyannis SJ. Fulminant hepatitis after flutamide treatment. <span><span class="ref-journal">J Hepatol. </span>1994;<span class="ref-vol">20</span>:350–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8014445" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8014445</span></a>]<div>
|
||
<i>(Two men, ages 70 and 84 years, with prostate cancer developed jaundice 13 and 8 weeks after starting flutamide [bilirubin 17.7 and 25.2 mg/dL, ALT 768 and 473 U/L, Alk P 239 and 165 U/L with hepatic failure], slowly resolving in one and fatal outcome in the other [with massive necrosis on autopsy]; one case had abnormal and one had normal ALT levels during routine monitoring 4 weeks before presentation).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.prattichizzo.1994.392">Prattichizzo FA. Acute cholestatic hepatitis secondary to flutamide therapy. <span><span class="ref-journal">Am J Med. </span>1994;<span class="ref-vol">96</span>:392–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8166163" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8166163</span></a>]<div>
|
||
<i>(Elderly man with prostate cancer developed jaundice 12 weeks after starting flutamide [bilirubin 16.7 mg/dL, ALT 1204 U/L, Alk P 341 U/L], resolving within 2 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.kosar.1995.1027">Kosar Y, Sasmaz N, Oguz P, Küçükbas S. Hepatic insufficiency developing as a result of flutamide treatment. <span><span class="ref-journal">Am J Gastroenterol. </span>1995;<span class="ref-vol">90</span>:1027–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7771407" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7771407</span></a>]<div>
|
||
<i>(58 year old man with prostate cancer developed jaundice 6 weeks after starting flutamide [bilirubin 11 mg/dL, ALT 348 U/L, Alk P 276 U/L, protime 34% and ascites], nevertheless, recovering within one month of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.moghetti.1995.511">Moghetti P, Castello R, Negri C, Tosi F, Magnani CM, Fontanarosa MC, Armanini D, et al. Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor behavior. <span><span class="ref-journal">Fertil Steril. </span>1995;<span class="ref-vol">64</span>:511–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7641903" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7641903</span></a>]<div>
|
||
<i>(18 women with hirsutism were treated with flutamide [125 mg/day] for 12 months; one developed asymptomatic rise in ALT [without jaundice] at 8 months [peak value ~140 U/L], falling promptly with stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.andr_jak.1996.121">Andréjak M, Nguyen-Khac E, Decocq G, Capron JP. <span><span class="ref-journal">Gastroenterol Clin Biol. </span>1996;<span class="ref-vol">20</span>:121–2.</span> [Fulminant hepatitis caused by flutamide] French. [<a href="https://pubmed.ncbi.nlm.nih.gov/8734324" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8734324</span></a>]<div>
|
||
<i>(70 year old man with prostate cancer developed jaundice 10 weeks after starting flutamide [bilirubin 10 times and ALT 49 times ULN], later developing ascites, encephalopathy and dying 6 weeks after presentation).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.cicognani.1996.2219">Cicognani C, Malavolti M, Morselli-Labate AM, Sama C, Barbara L. Flutamide-induced toxic hepatitis. Potential utility of ursodeoxycholic acid administration in toxic hepatitis. <span><span class="ref-journal">Dig Dis Sci. </span>1996;<span class="ref-vol">41</span>:2219–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8943975" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8943975</span></a>]<div>
|
||
<i>(83 year old man with prostate cancer developed jaundice 7 months after starting flutamide [bilirubin 24.5 mg/dL, ALT 1340 U/L, Alk P 319 U/L], resolving within 6 weeks off stopping with ursodiol treatment).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.crownover.1996.911">Crownover RL, Holland J, Chen A, Krieg R, Young BK, Roach M III, Fu KK. Flutamide-induced liver toxicity including fatal hepatic necrosis. <span><span class="ref-journal">Int J Radiat Oncol Biol Phys. </span>1996;<span class="ref-vol">34</span>:911–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8598370" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8598370</span></a>]<div>
|
||
<i>(Case reports of 3 men with prostate cancer receiving flutamide; 78 year old developed jaundice 2 months after starting [bilirubin 24.3 mg/dL, ALT 759 U/L and, Alk P 141 U/L] with fatal outcome; 63 and 70 year olds found to have abnormal liver tests 5 and 6 weeks after starting [bilirubin 0.8 and 1.1 mg/dL, ALT 258 and 77 U/L, Alk P 70 and 120 U/L], subsequent rapid recovery upon stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.lee.1996.225">Lee HW, Chung JP, Lee KS, Kim KC, Lee KS, Chon CY, Park IS, Kim HG. A case of flutamide-induced acute cholestatic hepatitis--a case report. <span><span class="ref-journal">Yonsei Med J. </span>1996;<span class="ref-vol">37</span>:225–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8826789" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8826789</span></a>]<div>
|
||
<i>(75 year old man with prostate cancer developed jaundice 7 months after starting flutamide [bilirubin 6.5 mg/dL, ALT 315 U/L, Alk P 470 U/L], resolving within 2 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.patel.1996.123">Patel H, Rhee E, Zimmern PE. <span><span class="ref-journal">J Urol (Paris). </span>1996;<span class="ref-vol">102</span>:123–5.</span> [Hepatic encephalopathy induced by flutamide administered for the treatment of prostatic cancer] French. [<a href="https://pubmed.ncbi.nlm.nih.gov/9091557" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9091557</span></a>]<div>
|
||
<i>(77 year old man with metastatic prostate cancer developed progressive fatigue, jaundice and confusion 1 month after starting flutamide [bilirubin 17 mg/dL, ALT 2,280 U/L], but with rapid improvement in mental status after stopping flutamide and normal values 6 months later while still on leuprolide).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.rosenthal.1996.451">Rosenthal SA, Linstadt DE, Leibenhaut MH, Andras EJ, Brooks CP, Stickney DR, Chang GC, et al. Flutamide-associated liver toxicity during treatment with total androgen suppression and radiation therapy for prostate cancer. <span><span class="ref-journal">Radiology. </span>1996;<span class="ref-vol">199</span>:451–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8668793" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8668793</span></a>]<div>
|
||
<i>(Prospective study of liver tests in 65 prostate cancer patients given flutamide and goserelin for 4 months; ALT rose above normal in 62%, and to >5 times ULN in 7%; 14 patients stopped therapy early because of ALT levels; 2 patients developed hepatitis [bilirubin 3.9 and 3.8 mg/dL, ALT 1116 and 816 U/L], all resolved within 3 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.wysowski.1996.209">Wysowski DK, Fourcroy JL. Flutamide hepatotoxicity. <span><span class="ref-journal">J Urol. </span>1996;<span class="ref-vol">155</span>:209–12.</span> Erratum in: J Urol 1996; 155: 1396. [<a href="https://pubmed.ncbi.nlm.nih.gov/7490837" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7490837</span></a>]<div>
|
||
<i>(Review of flutamide events reported to FDA MedWatch 1989-1994, found 20 deaths and 26 hospitalizations for flutamide hepatotoxicity ~3/10,000; autopsy in 6 showed massive necrosis, mean onset of 3 months after starting; found 16 cases in literature).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.cantalejo_moreira.1997.819">Cantalejo Moreira M, García Espinosa V, Martín Gutiérrez JC, García Puig J. <span><span class="ref-journal">Med Clin (Barc). </span>1997;<span class="ref-vol">109</span>:819–20.</span> [Hepatotoxicity from flutamide] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/9493165" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9493165</span></a>]<div>
|
||
<i>(82 year old man with prostate cancer developed jaundice 6 months after starting flutamide [bilirubin 22.7 mg/dL, ALT 686 U/L, Alk P 691 U/L], with rapid recovery within 1 month of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.fern_ndez_pe_a.1997.237">Fernández Peña CM, Morano Amado LE, Montes Santiago J, Fachal C. <span><span class="ref-journal">Med Clin (Barc). </span>1997;<span class="ref-vol">108</span>:237–8.</span> [Fulminant liver failure with a fatal outcome due to flutamide] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/9102495" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9102495</span></a>]<div>
|
||
<i>(68 year old man with metastatic prostate cancer developed jaundice 3 months after starting flutamide and LHRH analog therapy [bilirubin 17.4 mg/dL, ALT 1429 U/L, Alk P 8679 U/L, protime 66%]; despite stopping therapy promptly, he developed liver failure and died within a month of presentation).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.garc_agasc_.1997.820">García-Gascó P, Morata Aldea C, Segura Huertas A, Aparicio Urtasun J. <span><span class="ref-journal">Med Clin (Barc). </span>1997;<span class="ref-vol">109</span>:820.</span> [Fulminant hepatitis associated with treatment with flutamide] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/9493166" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9493166</span></a>]<div>
|
||
<i>(80 year old man with prostate cancer developed jaundice 4 months after starting flutamide therapy [bilirubin 27 mg/dL, ALT 781 U/L, Alk P 590 U/L, protime 41%]; rapid progression despite stopping drug to liver failure and death within 15 days).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.guzm_n_mart_nezvalls.1997.278">Guzmán Martínez-Valls PL, Ferrero Doria R, Morga Egea JP, Ros R, Galiano R, Gutierrez A, Franco G, et al. <span><span class="ref-journal">Actas Urol Esp. </span>1997;<span class="ref-vol">21</span>:278–82.</span> [Liver failure caused by flutamide] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/9324896" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9324896</span></a>]</div></li><li><div class="bk_ref" id="Flutamide.REF.mcleod.1997.18">McLeod DG. Tolerability of nonsteroidal antiandrogens in the treatment of advanced prostate cancer. <span><span class="ref-journal">Oncologist. </span>1997;<span class="ref-vol">2</span>:18–27.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10388026" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10388026</span></a>]<div>
|
||
<i>(Overview of the safety and side effects of the nonsteroidal antiandrogens; ALT elevations arise in 4-62% receiving flutamide; in comparison studies, 12% with flutamide vs 3% with placebo and 10% vs 6% with bicalutamide; clinically apparent hepatitis can occur and can be fatal; estimated rates being 3/10,000 treated).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.satoh.1997.694">Satoh T, Egawa S, Katsuta M, Iwamura M, Uchida T, Koshiba K. <span><span class="ref-journal">Nippon Hinyokika Gakkai Zasshi. </span>1997;<span class="ref-vol">88</span>:694–6.</span> [A case of fulminant hepatitis caused by antiandrogen, flutamide in a patient with prostate cancer] Japanese. [<a href="https://pubmed.ncbi.nlm.nih.gov/9267134" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9267134</span></a>]<div>
|
||
<i>(Abstract only: 66 year old man with metastatic prostate cancer developed jaundice 7 weeks after starting flutamide [375 mg/day], resolving within 2 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.wietzke.1997.631">Wietzke P, Münke H, Hartmann H, Ramadori G. <span><span class="ref-journal">Z Gastroenterol. </span>1997;<span class="ref-vol">35</span>:631–5.</span> [Hepatotoxicity of flutamide] German. [<a href="https://pubmed.ncbi.nlm.nih.gov/9381745" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9381745</span></a>]<div>
|
||
<i>(Two cases of jaundice in men, ages 76 and 64 years, with prostate cancer given flutamide for 16 and 8 weeks [bilirubin 8.9 and 8.4 mg/dL, ALT 699 and 612 U/L, Alk P 206 and 241 U/L, one patient with ascites], resolving within 9-10 weeks of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.chu.1998.678">Chu CW, Hwang SJ, Luo JC, et al. Flutamide-induced liver injury: a case report. <span><span class="ref-journal">Zhonghua Yi Xue Za Zhi (Taipei). </span>1998;<span class="ref-vol">61</span>:678–82.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9872026" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9872026</span></a>]<div>
|
||
<i>(72 year old man with prostate cancer developed jaundice 5 months after starting flutamide [bilirubin 7.0 mg/dL, ALT 1035 U/L, Alk P 145 U/L], resolving within 3 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.cuevas_campos.1998.499">Cuevas Campos MA, Pareja Llorens G, García Romero E, Bertomeu Blanch F. <span><span class="ref-journal">Gastroenterol Hepatol. </span>1998;<span class="ref-vol">21</span>:499–500.</span> [Toxic hepatitis caused by flutamide] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/9927799" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9927799</span></a>]<div>
|
||
<i>(67 year old man with prostate cancer developed jaundice 2 months after starting flutamide [bilirubin 11.2 mg/dL, ALT 1050 U/L, Alk P 381 U/L], resolving promptly upon stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.mena.1998.376">Mena FJ, Goyeneche ML, Velicia R, González JM, Bellido J, Caro-Patón A. <span><span class="ref-journal">Rev Esp Enferm Dig. </span>1998;<span class="ref-vol">90</span>:376–7.</span> [Acute cholestatic hepatitis secondary to flutamide] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/9656761" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9656761</span></a>]<div>
|
||
<i>(Two men, ages 77 and 69 years, with prostate cancer treated with flutamide and leuprolide for 4-5 months presented with jaundice [bilirubin 9.7 and 6.0 mg/dL, ALT 1058 and 1073 U/L, Alk P 620 and 459 U/L], resolving within 7 to 8 weeks of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.pogromov.1998.56">Pogromov AP, Popova AM. <span><span class="ref-journal">Klin Med (Mosk). </span>1998;<span class="ref-vol">76</span>:56–8.</span> [The hepatotoxicity of flutamide] Russian. [<a href="https://pubmed.ncbi.nlm.nih.gov/9742783" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9742783</span></a>]</div></li><li><div class="bk_ref" id="Flutamide.REF.pontiroli.1998.310">Pontiroli L, Sartori M, Pittau S, Morelli S, Boldorini R, Albano E. Flutamide-induced acute hepatitis: investigation on the role of immunoallergic mechanisms. <span><span class="ref-journal">Ital J Gastroenterol Hepatol. </span>1998;<span class="ref-vol">30</span>:310–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9759603" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9759603</span></a>]<div>
|
||
<i>(69 year old man with prostate cancer developed jaundice 4 months after starting flutamide therapy [bilirubin 14.1 mg/dL, ALT 946 U/L, Alk P 352 U/L], resolving rapidly upon stopping; tests for antibodies to flutamide-treated rat microsomes were negative).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.andrade.1999.983">Andrade RJ, Lucena MI, Fernández MC, Suarez F, Montero JL, Fraga E, Hidalgo F. Fulminant liver failure associated with flutamide therapy for hirsutism. <span><span class="ref-journal">Lancet. </span>1999;<span class="ref-vol">353</span>:983.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10459914" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10459914</span></a>]<div>
|
||
<i>(14 year old girl developed jaundice 3 months after starting therapy with flutamide for acne [bilirubin 7.3 mg/dL, ALT 2372 U/L], with subsequent liver failure requiring transplantation; explant showed massive necrosis: Case 1).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.cetin.1999.137">Cetin M, Demirci D, Unal A, Altinbas M, Güven M, Unlühizarci K. Frequency of flutamide induced hepatotoxicity in patients with prostate carcinoma. <span><span class="ref-journal">Hum Exp Toxicol. </span>1999;<span class="ref-vol">18</span>:137–40.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10215102" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10215102</span></a>]<div>
|
||
<i>(Prospective study of 22 patients with prostate cancer; two patients [9%] developed jaundice 5 and 8 weeks after starting flutamide [bilirubin 3.0 and 9.6 mg/dL, ALT 380 and 284 U/L, Alk P 1289 and 864 U/L]; one resolving within 4 weeks of stopping, the second being fatal).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.falsetti.1999.361">Falsetti L, Gambera A, Legrenzi L, Iacobello C, Bugari G. Comparison of finasteride versus flutamide in the treatment of hirsutism. <span><span class="ref-journal">Eur J Endocrinol. </span>1999;<span class="ref-vol">141</span>:361–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10526249" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10526249</span></a>]<div>
|
||
<i>(Controlled trial of finasteride [5 mg/day] vs flutamide [500 mg/day] for 12 months in 110 women with hirsutism; 2 patients on flutamide [4%] developed ALT elevations after 6 months, both resolving with stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.nakagawa.1999.821">Nakagawa Y, Koyama M, Matsumoto M. <span><span class="ref-journal">Hinyokika Kiyo. </span>1999;<span class="ref-vol">45</span>:821–6.</span> [Flutamide-induced hepatic disorder and serum concentrations of flutamide and its metabolites in patients with prostate cancer] Japanese. [<a href="https://pubmed.ncbi.nlm.nih.gov/10659414" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10659414</span></a>]<div>
|
||
<i>(Case report of severe hepatotoxicity after 11 weeks of flutamide therapy associated with high levels of metabolites; among 37 men with prostate cancer treated with flutamide, minor ALT elevations occurred in 7 [19%], rapidly resolving; >100 U/L in 2 patients).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.nicol_s.1999.262">Nicolás D. Pérez-EbrI ML, Sarrión JV, Nos P. <span><span class="ref-journal">Gastroenterol Hepatol. </span>1999;<span class="ref-vol">22</span>:262–3.</span> [Acute flutamide-induced hepatitis] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/10396113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10396113</span></a>]<div>
|
||
<i>(73 year old man with prostate cancer developed jaundice 10 months after starting flutamide and an LHRH analog [bilirubin 6.7 mg/dL, ALT 697 U/L, Alk P 164 U/L, protime 45% and mild ascites], resolving within 3-5 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.okaneya.1999.590">Okaneya T, Murata Y, Kinebuchi Y. <span><span class="ref-journal">Nippon Hinyokika Gakkai Zasshi. </span>1999;<span class="ref-vol">90</span>:590–3.</span> [Fatal hepatic failure following hepatitis caused by flutamide: a case report] Japanese. [<a href="https://pubmed.ncbi.nlm.nih.gov/10386060" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10386060</span></a>]<div>
|
||
<i>(73 year old man with prostate cancer developed flutamide hepatotoxicity [ALT 3045 U/L] and died of complications of duodenal ulcer bleeding [abstract only]).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.pu.1999.293">Pu YS, Liu CM, Kao JH, Chen J, Lai MK. Antiandrogen hepatotoxicity in patients with chronic viral hepatitis. <span><span class="ref-journal">Eur Urol. </span>1999;<span class="ref-vol">36</span>:293–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10473987" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10473987</span></a>]<div>
|
||
<i>(Retrospective study of 121 men receiving antiandrogen therapy with flutamide or cyproterone found abnormal ALT levels in most or all who were HBsAg or anti-HCV-positive; but many were not tested, and frequency of ALT monitoring was unclear. Authors propose that antiandrogen hepatotoxicity is more frequent among men with preexisting hepatitis, but no attempt was made to separate hepatotoxicity from exacerbation of underlying disease).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.wada.1999.521">Wada T, Ueda M, Abe K, Kobari T, Yamazaki H, Nakata J, Ikemoto I, et al. <span><span class="ref-journal">Hinyokika Kiyo. </span>1999;<span class="ref-vol">45</span>:521–6.</span> [Risk factor of liver disorders caused by flutamide--statistical analysis using multivariate logistic regression analysis] Japanese. [<a href="https://pubmed.ncbi.nlm.nih.gov/10500955" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10500955</span></a>]<div>
|
||
<i>(Among 123 men with prostate cancer treated with flutamide, 33 [26%] developed "liver disorders;" rate was higher in those with previous histories of liver disease and preexisting elevations in GGT or ALT [abstract only]).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.ikemoto.2000.556">Ikemoto I, Ohishi Y, Yamazaki H, Wada T, Aizawa Y. <span><span class="ref-journal">Nippon Hinyokika Gakkai Zasshi. </span>2000;<span class="ref-vol">91</span>:556–61.</span> [Changes in liver function induced by flutamide in patients with prostate cancer (studies in patients treated with total androgen blockage)] Japanese. [<a href="https://pubmed.ncbi.nlm.nih.gov/10897581" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10897581</span></a>]<div>
|
||
<i>(Prospective study of ALT elevations in 50 patients with prostate cancer receiving flutamide; 12 patients developed abnormalities which were severe in 2 [4%] and with only mild bilirubin elevations [abstract only]).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.rom_n_llorente.2000.258">Román Llorente FJ, Alvarez Navascués C, Suárez González A, González Bernal AC. <span><span class="ref-journal">Gastroenterol Hepatol. </span>2000;<span class="ref-vol">23</span>:258.</span> [Toxic hepatitis caused by flutamide and hirsutism] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/10902281" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10902281</span></a>]<div>
|
||
<i>(23 year old woman treated with flutamide [500 mg/day] for hirsutism for 5 months developed jaundice [bilirubin 26.6 mg/dL, ALT 1268 U/L, Alk P 119 U/L], resolving within 3 months of withdrawal).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.garc_a_cort_s.2001.423">García Cortés M, Andrade RJ, Lucena MI, Sanchez Martinez H, Fernandez MC, Ferrer T, Martin-Vivaldi R, et al. Flutamide-induced hepatotoxicity: report of a case series. <span><span class="ref-journal">Rev Esp Enferm Dig. </span>2001;<span class="ref-vol">93</span>:423–32.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11685939" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11685939</span></a>]<div>
|
||
<i>(Spanish registry from 1994-2000 contained 9 cases [5%] of flutamide hepatotoxicity; 8 were men, mean age 75 years, no autoantibodies, no eosinophilia, latency to onset of 4 to 433 days [mean=151 days], usually with hepatocellular pattern of enzyme elevations; 2 deaths).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.kraus.2001.395">Kraus I, Vitezic D, Oguic R. Flutamide-induced acute hepatitis in advanced prostate cancer patients. <span><span class="ref-journal">Int J Clin Pharmacol Ther. </span>2001;<span class="ref-vol">39</span>:395–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11563686" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11563686</span></a>]<div>
|
||
<i>(3 cases of jaundice arising 20-22 weeks after starting flutamide therapy for prostate cancer [bilirubin 16.8, 24.6 and 10 mg/dL, ALT 750, 670 and 854 U/L, Alk P 158, 411 and 238 U/L], all 3 resolving within 2 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.ruiz.2001.565">Ruiz R, Casañ R, Juan O. <span><span class="ref-journal">Aten Primaria. </span>2001;<span class="ref-vol">28</span>:565.</span> [Hepatotoxicity due to flutamide] Spanish. [<a href="/pmc/articles/PMC7681665/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7681665</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11792276" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11792276</span></a>]<div>
|
||
<i>(74 year old man with prostate cancer developed jaundice 6 months after starting flutamide [bilirubin 11.1 mg/dL, ALT 806 U/L, GGT 689 U/L], severe course but ultimately resolved).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.ruizrebollo.2001.218">Ruiz-Rebollo M, Atienza-Sánchez R, López-García E. <span><span class="ref-journal">Gastroenterol Hepatol. </span>2001;<span class="ref-vol">24</span>:218.</span> [Hirsutism, flutamide and hepatotoxicity] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/11333662" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11333662</span></a>]<div>
|
||
<i>(23 year old woman with hirsutism treated with flutamide [500 mg/day] for 4 months developed abdominal pain and jaundice [bilirubin 22.4 mg/dL, ALT 1618 U/L, Alk P 422 U/L], relapsing upon inadvertent reintroduction of flutamide [bilirubin rising to 46.7 mg/dL, ALT 965 U/L, Alk P 459 U/L], but then resolution within 4 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.venturoli.2001.25">Venturoli S, Paradisi R, Bagnoli A, Colombo FM, Ravaioli B, Vianello F, Mancini F, et al. Low-dose flutamide (125 mg/day) as maintenance therapy in the treatment of hirsutism. <span><span class="ref-journal">Horm Res. </span>2001;<span class="ref-vol">56</span>:25–31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11815724" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11815724</span></a>]<div>
|
||
<i>(Trial of flutamide [250 for 12 months followed by 125 mg/day for 12 months] in 47 women with hirsutism found ALT elevations in 4 [9%] during first 2 months, thereafter no further ALT elevations or liver toxicity observed).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.ozono.2002.128">Ozono S, Yamaguchi A, Mochizuki H, Kawakami T, Fujimoto K, Otani T, Yoshida K, et al. Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer. <span><span class="ref-journal">Prostate Cancer Prostatic Dis. </span>2002;<span class="ref-vol">5</span>:128–31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12497002" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12497002</span></a>]<div>
|
||
<i>(Study of patients who received flutamide for prostate cancer found that the 9 with ALT elevations had decreased caffeine metabolism compared to 2 who did not, suggesting a role for CYP1A2).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.aizawa.2003.149">Aizawa Y, Ikemoto I, Kishimoto K, Wada T, Yamazaki H, Ohishi Y, Kiyota H, et al. Flutamide-induced hepatic dysfunction in relation to steady-state plasma concentrations of flutamide and its metabolites. <span><span class="ref-journal">Mol Cell Biochem. </span>2003;<span class="ref-vol">252</span>:149–56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14577588" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14577588</span></a>]<div>
|
||
<i>(Prospective study of 55 patients with prostate cancer treated with flutamide, found higher levels of metabolite [FLU-1] in 2 patients who developed hepatotoxicity compared to others).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.ashar.2003.75">Ashar U, Desai D, Bhaduri A. Flutamide-induced hepatotoxicity with possible potentiation by simvastatin. <span><span class="ref-journal">J Assoc Physicians India. </span>2003;<span class="ref-vol">51</span>:75–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12693464" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12693464</span></a>]<div>
|
||
<i>(65 year old man with prostate cancer developed jaundice 8-9 months after starting flutamide [bilirubin 24 mg/dL, ALT 646 U/L, Alk P 290 U/L]; jaundice lasted 2 months but ultimately there was full recovery within 4 months of stopping: Case 2).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.famularo.2003.250">Famularo G, De Simone C, Minisola G, Nicotra GC. Flutamide-associated acute liver failure. <span><span class="ref-journal">Ann Ital Med Int. </span>2003;<span class="ref-vol">18</span>:250–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14971714" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14971714</span></a>]<div>
|
||
<i>(74 year old man with prostate cancer developed jaundice 2 months after starting flutamide [bilirubin 26 mg/dL, ALT 2372 U/L, Alk P 3 times ULN, INR 2.3 and ascites], resolving slowly and incompletely over the next 10 months).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.kackar.2003.149">Kackar RR, Desai HG. Hepatic failure with flutamide. <span><span class="ref-journal">Indian J Gastroenterol. </span>2003;<span class="ref-vol">22</span>:149–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12962443" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12962443</span></a>]<div>
|
||
<i>(41 year old woman with hair loss developed fever and jaundice 3 months after starting flutamide [bilirubin 2.3 rising to 24.4 mg/dL, ALT 1800 U/L, Alk P 183 U/L, rising INR, ascites and coma], but ultimately recovering spontaneously without transplantation).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.lin.2003.735">Lin AD, Chen KK, Lin AT, Chang Y-H, Wu HHH, Kuo J-Y, Huang WJS, et al. Antiandrogen-associated hepatotoxicity in the management of advanced prostate cancer. <span><span class="ref-journal">J Chin Med Assoc. </span>2003;<span class="ref-vol">66</span>:735–40.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15015823" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15015823</span></a>]<div>
|
||
<i>(Retrospective review of 229 patients with prostate cancer treated with flutamide or cyproterone and a LHRH agonist, orchiectomy or radiotherapy with regular monitoring of ALT; ALT >2 times ULN arose in 15.3% of flutamide and 9.5% of cyproterone treated subjects; ALT >6 times ULN in 5% vs 4%; no deaths, a few had jaundice).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.takashima.2003.1455">Takashima E, Iguchi K, Usui S, Yamamoto H, Hirano K. Metabolite profiles of flutamide in serum from patients with flutamide-induced hepatic dysfunction. <span><span class="ref-journal">Biol Pharm Bull. </span>2003;<span class="ref-vol">26</span>:1455–60.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14519954" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14519954</span></a>]<div>
|
||
<i>(Analysis of metabolic products of flutamide; pattern found to be similar in patients with and without ALT elevations).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.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 done in the US between 1990 and 2002, 270 [0.5%] were done for drug induced acute liver failure, but no case was attributed to an antiandrogen, perhaps because patients with prostate cancer were less likely to be eligible for liver transplantation).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.l_bbert.2004.333">Lübbert C, Wiese M, Haupt R, Ruf BR. <span><span class="ref-journal">Internist (Berl). </span>2004;<span class="ref-vol">45</span>:333–40.</span> [Toxic hepatitis and liver failure under therapy with flutamide] German. [<a href="https://pubmed.ncbi.nlm.nih.gov/14997310" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14997310</span></a>]<div>
|
||
<i>(77 and 66 year old men with prostate cancer developed jaundice 4 and 12 weeks after starting flutamide [bilirubin 13.6 and 25 mg/dL, ALT 1825 and 2145 U/L, Alk P 1.5 and 3 times ULN], one resolving within 4 weeks of stopping and the other progressing to liver failure and death: Case 3).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.manolakopoulos.2004.462">Manolakopoulos S, Bethanis S, Armonis A, Economou M, Avgerinos A, Tzourmakliotis D. Toxic hepatitis after sequential administration of flutamide and cyproterone acetate. <span><span class="ref-journal">Dig Dis Sci. </span>2004;<span class="ref-vol">49</span>:462–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15139499" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15139499</span></a>]<div>
|
||
<i>(76 year old man with prostate cancer developed jaundice 6 months after starting flutamide [bilirubin 23.6 mg/dL, ALT 164 U/L, Alk P 132 U/L], which recurred 5 months after switching to cyproterone [bilirubin 6.8 mg/dL, ALT 162 U/L, Alk P 302], having a similar time course of recovery).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.thole.2004.289">Thole Z, Manso G, Salgueiro E, Revuelta P, Hidalgo A. Hepatotoxicity induced by antiandrogens: a review of the literature. <span><span class="ref-journal">Urol Int. </span>2004;<span class="ref-vol">73</span>:289–95.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15604569" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15604569</span></a>]<div>
|
||
<i>(Systematic review of the literature from the Spanish pharmacovigilance group; 21 reports of hepatotoxicity on cyproterone, 46 flutamide, 4 nilutamide and only 1 bicalutamide; 6 cases of hepatocellular carcinoma linked to cyproterone therapy).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.v_zquez_romero.2004.307">Vázquez Romero M, Gil Grande L, López Serrano P, Alemán Villanueva S, García Plaza A. <span><span class="ref-journal">An Med Interna. </span>2004;<span class="ref-vol">21</span>:307–8.</span> [Liver toxicity associated with flutamide] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/15283649" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15283649</span></a>]<div>
|
||
<i>(82 year old man with prostate cancer developed jaundice 2-3 months after starting flutamide and leuprolide [bilirubin 13.6 mg/dL, ALT 1369 U/L, GGT 586 U/L], with rapid recovery upon stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.bengoechea_gallastegui.2005.112">Bengoechea Gallastegui L, Vita Garay A, Castiella Eguzkiza A, Egido Arroyo JF. <span><span class="ref-journal">Aten Primaria. </span>2005;<span class="ref-vol">36</span>:112.</span> [Toxic hepatitis after flutamide treatment] Spanish. [<a href="/pmc/articles/PMC7676060/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7676060</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15989835" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15989835</span></a>]<div>
|
||
<i>(68 year old man with prostate cancer and HBsAg carrier state [HBV DNA 10,100 copies/mL, HBeAg negative] developed elevated ALT [1474 U/L] and GGT [540 U/L] 30 weeks after starting flutamide therapy, rapid recovery upon stopping; no mention of jaundice).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.ib__ez.2005.1833">Ibáñez L, Jaramillo A, Ferrer A, de Zegher F. Absence of hepatotoxicity after long-term, low-dose flutamide in hyperandrogenic girls and young women. <span><span class="ref-journal">Hum Reprod. </span>2005;<span class="ref-vol">20</span>:1833–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15802316" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15802316</span></a>]<div>
|
||
<i>(Prospective study of long term flutamide in doses of 62.5, 125 and 250 mg daily in 190 women with hirsutism, found no ALT elevations during routine screening, suggesting that flutamide hepatotoxicity is partially dose related).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.legro.2006.188">Legro RS. Long-term, low-dose flutamide does not cause hepatotoxicity in hyperandrogenic women. <span><span class="ref-journal">Nat Clin Pract Endocrinol Metab. </span>2006;<span class="ref-vol">2</span>:188–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16932279" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16932279</span></a>]<div>
|
||
<i>(Editorial on study by Ibanez [2005] expressing caution about using flutamide particularly in view of potential of fetal toxicity in young women).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.papaioannides.2005.515">Papaioannides D, Korantzopoulos P, Bouropoulos C, Latsi P, Fotinou M, Orphanidou D. Microscopic polyangiitis complicated by the development of prostate cancer and flutamide-induced hepatitis. <span><span class="ref-journal">Int Urol Nephrol. </span>2005;<span class="ref-vol">37</span>:515–20.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16307333" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16307333</span></a>]<div>
|
||
<i>(65 year old man on long term cyclophosphamide developed prostate cancer and then became jaundiced 6 months after starting flutamide [bilirubin 12.5 mg/dL, ALT 480 U/L, Alk P 410 U/L], resolving within 6 weeks of stopping; later developed gastric cancer).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.ram_rez.2005.433">Ramírez R, Ruiz MA, Auguet T, Richart C. <span><span class="ref-journal">Gastroenterol Hepatol. </span>2005;<span class="ref-vol">28</span>:433.</span> [Severe acute hepatitis due to flutamide and elevated CA 19.9] Spanish. [<a href="https://pubmed.ncbi.nlm.nih.gov/16137480" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16137480</span></a>]<div>
|
||
<i>(91 year old man developed jaundice and confusion 6 months after starting flutamide for prostatism [bilirubin 9.4 mg/dL, ALT 342 U/L, GGT 223 U/L, ammonia 420 μmol/L], but with ultimate full recovery within 6 weeks of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.manso.2006.253">Manso G, Thole Z, Salgueiro E, Revuelta P, Hidalgo A. Spontaneous reporting of hepatotoxicity associated with antiandrogens: data from the Spanish pharmacovigilance system. <span><span class="ref-journal">Pharmacoepidemiol Drug Saf. </span>2006;<span class="ref-vol">15</span>:253–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16294367" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16294367</span></a>]<div>
|
||
<i>(Analysis of spontaneous reporting to Spanish Pharmacovigilance system found 88 cases of flutamide, 11 bicalutamide and 15 cyproterone hepatotoxicity, latency 3-6 months; 2 fatalities, both from flutamide).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.bj_rnsson.2006.33">Björnsson E, Olsson R. Suspected drug-induced liver fatalities reported to the WHO database. <span><span class="ref-journal">Dig Liver Dis. </span>2006;<span class="ref-vol">38</span>:33–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16054882" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16054882</span></a>]<div>
|
||
<i>(Survey of drug induced liver fatalities reported to WHO database between 1968-2003 revealed 4690 reports; flutamide ranked 11th with a total of 59 cases).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.osculati.2006.1140">Osculati A, Castiglioni C. Fatal liver complications with flutamide. <span><span class="ref-journal">Lancet. </span>2006;<span class="ref-vol">367</span>:1140–1.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16616550" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16616550</span></a>]<div>
|
||
<i>(18 year old woman developed jaundice 5 months after starting flutamide therapy of acne [bilirubin 13 rising to 32 mg/dL, ALT 4717 U/L, GGT 140 U/L], with progressive hepatic failure, liver transplantation but death in perioperative period due to sepsis).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.miquel.2007.1144">Miquel M, Soler A, Vaqué A, Ojanguren I, Costa J, Planas R. Suspected cross-hepatotoxicity of flutamide and cyproterone acetate. <span><span class="ref-journal">Liver Int. </span>2007;<span class="ref-vol">27</span>:1144–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17845544" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17845544</span></a>]<div>
|
||
<i>(78 year old man with prostate cancer developed jaundice 3 months after starting flutamide [bilirubin 20.9 mg/dL, ALT 262 U/L, Alk P 104 U/L], resolving upon stopping, but recurring within 2 months of switching to cyproterone [bilirubin 15.6 mg/dL, ALT 373 U/L, Alk P 70 U/L], similar course of recovery).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.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 an antiandrogen).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.castelo_branco.2009.1183">Castelo Branco C, Moyano D, Gomez O, Balasch J. Long-term safety and tolerability of flutamide for the treatment of hirsutism. <span><span class="ref-journal">Fertil Steril. </span>2009;<span class="ref-vol">91</span>:1183–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18339379" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18339379</span></a>]<div>
|
||
<i>(Prospective study of use of flutamide with or without estrogens in 83 women with hirsutism; side effects were common, two women developed ALT elevations but no details given).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.wang.2009.195">Wang YP, Shi B, Chen YX, Xu J, Jiang CF, Xie WF. Drug-induced liver disease: an 8-year study of patients from one gastroenterological department. <span><span class="ref-journal">J Dig Dis. </span>2009;<span class="ref-vol">10</span>:195–200.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19659787" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19659787</span></a>]<div>
|
||
<i>(Among 30 patients with drug induced liver injury seen at a single medical center in Beijing between 2000 and 2007, one case was due to flutamide; ALT 8 times ULN, Alk P normal, bilirubin 12.7 mg/dL arising 12 weeks after starting drug).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.dikensoy.2009.321">Dikensoy E, Balat O, Pence S, Akcali C, Cicek H. The risk of hepatotoxicity during long-term and low-dose flutamide treatment in hirsutism. <span><span class="ref-journal">Arch Gynecol Obstet. </span>2009;<span class="ref-vol">279</span>:321–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18607612" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18607612</span></a>]<div>
|
||
<i>(Prospective trial of 12 month course of low dose flutamide [50-250 mg/day], with ALT monitoring every 3 months in 214 women with hirsutism; none developed abnormal ALT or AST).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.de_zegher.2009.83">de Zegher F, Ibáñez L. Low-dose flutamide for women with androgen excess: anti-androgenic efficacy and hepatic safety. <span><span class="ref-journal">J Endocrinol Invest. </span>2009;<span class="ref-vol">32</span>:83–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19337022" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19337022</span></a>]<div>
|
||
<i>(Opinion article suggesting that low dose flutamide [62.5-125 mg/day] can be safely and effectively used to treat hirsutism and acne in women with androgen excess, no ALT elevations having been reported in 286 women on 62.5 mg and 166 on 125 mg daily for at least 12 months).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.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 were attributed to antiandrogen therapies).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.paradisi.2010.139">Paradisi R, Venturoli S. Retrospective observational study on the effects and tolerability of flutamide in a large population of patients with various kinds of hirsutism over a 15-year period. <span><span class="ref-journal">Eur J Endocrinol. </span>2010;<span class="ref-vol">163</span>:139–47.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20371655" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20371655</span></a>]<div>
|
||
<i>(Among 414 women with hirsutism treated with flutamide in yearly decreasing doses, 25 [6%] developed ALT elevations, all without jaundice or symptoms, usually mild, arising during first year of therapy while on 250 mg/day, resolving rapidly on stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.paradisi.2011.823">Paradisi R, Fabbri R, Porcu E, Battaglia C, Seracchioli R, Venturoli S. Retrospective, observational study on the effects and tolerability of flutamide in a large population of patients with acne and seborrhea over a 15-year period. <span><span class="ref-journal">Gynecol Endocrinol. </span>2011;<span class="ref-vol">27</span>:823–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21117864" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21117864</span></a>]<div>
|
||
<i>(Among 230 women with acne treated with flutamide in yearly reducing doses, 11 [4.8%] discontinued therapy because of ALT elevations, all during the first year while on 250 mg/day, all resolving upon stopping treatment).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.paradisi.2011.469">Paradisi R, Porcu E, Fabbri R, Seracchioli R, Battaglia C, Venturoli S. Prospective cohort study on the effects and tolerability of flutamide in patients with female pattern hair loss. <span><span class="ref-journal">Ann Pharmacother. </span>2011;<span class="ref-vol">45</span>:469–75.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21487083" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21487083</span></a>]<div>
|
||
<i>(Among 101 women with female pattern hair loss treated with flutamide for up to 4 years, 4 [4%] discontinued therapy because of ALT elevations during the first year, but none for this reason in subsequent years when lower doses were used [125 and 62.5 mg/day], ALT elevations resolving rapidly after stopping in all).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.brahm.2011.93">Brahm J, Brahm M, Segovia R, Latorre R, Zapata R, Poniachik J, Buckel E, Contreras L. Acute and fulminant hepatitis induced by flutamide: case series report and review of the literature. <span><span class="ref-journal">Ann Hepatol. </span>2011;<span class="ref-vol">10</span>:93–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21301018" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21301018</span></a>]<div>
|
||
<i>(Analysis of 10 patients with flutamide hepatotoxicity seen at a single institution in Chile included 3 men [ages 67-80 with prostate cancer] and 7 women [ages 20-44 with hirsutism], onset in 40-180 days, 9 with jaundice [bilirubin 2.4-44 mg/dL, ALT 159-3360 U/L], 5 progressed to acute liver failure requiring liver transplantation [all women]).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.bruni.2012.1047">Bruni V, Peruzzi E, Dei M, Nannini S, Seravalli V, Sisti G, Fambrini M. Hepatotoxicity with low- and ultralow-dose flutamide: a surveillance study on 203 hyperandrogenic young females. <span><span class="ref-journal">Fertil Steril. </span>2012;<span class="ref-vol">98</span>:1047–52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22795685" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22795685</span></a>]<div>
|
||
<i>(Among 203 young women with polycystic ovary syndrome treated with low doses of flutamide [62.5 or 125 mg/day] for up to 5 years, ALT or AST elevations [43-509 U/L] occurred in 9% during the first year [arising after 2 to 48 weeks], with resolution within 4 weeks of stopping in all; no mention of jaundice or symptoms).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.karaahmet.2012.e27">Karaahmet F, Kurt K. Hepatotoxicity with flutamide. <span><span class="ref-journal">Fertil Steril. </span>2012;<span class="ref-vol">98</span>:e27. </span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22985946" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22985946</span></a>]<div>
|
||
<i>(Letter in response to Bruni [2012] raising issue of definition of hepatotoxicity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.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>(2):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, the most common implicated agents being nimesulide [n=53: 30%], cyproterone [n=18], nitrofurantoin [n=17], antituberculosis drugs [n=13] and flutamide [n=12: 7%]).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.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 bicalutamide, but none to other antiandrogens such as flutamide).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.choudhary.2017.e12907">Choudhary NS, Saigal S, Saraf N, Rastogi A, Goja S, Bhangui P, Vohra V, et al. Good outcome of living donor liver transplantation in drug-induced acute liver failure: A single-center experience. <span><span class="ref-journal">Clin Transplant. </span>2017;<span class="ref-vol">31</span>:e12907. </span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28054388" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28054388</span></a>]<div>
|
||
<i>(Among 1396 adult living donor liver transplants done at a single referral center in India, 64 were done for acute liver failure including 18 caused by drugs; 14 by antituberculosis medications, 1 flutamide, 1 orlistat and 2 herbal supplements).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.castelobranco.2016.723">Castelo-Branco C, Hernández-Angeles C, Alvarez-Olivares L, Balasch J. Long-term satisfaction and tolerability with low-dose flutamide: a 20-year surveillance study on 120 hyperandrogenic women. <span><span class="ref-journal">Gynecol Endocrinol. </span>2016;<span class="ref-vol">32</span>:723–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27176209" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27176209</span></a>]<div>
|
||
<i>(Among 120 women with hyperandrogenism treated with flutamide [125 or 250 mg daily] for up to 20 years, 11 stopped therapy because of ALT abnormalities and one for acute fatty liver requiring hospitalization; timing and degree of abnormalities not provided).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Flutamide.REF.crawford.2018.956">Crawford ED, Schellhammer PF, McLeod DG, Moul JW, Higano CS, Shore N, Denis L, et al. Androgen receptor targeted treatments of prostate cancer: 35 years of progress with antiandrogens. <span><span class="ref-journal">J Urol. </span>2018;<span class="ref-vol">200</span>:956–966.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29730201" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29730201</span></a>]<div>
|
||
<i>(Review of the development of antiandrogen therapies of prostate cancer starting with discovery of the androgen sensitive nature of prostate cancer, the effects of orchiectomy, followed by the development of androgen receptor antagonists, first generation agents flutamide and nilutamide, second generation agent bicalutamide and third generation agents enzalutamide, apalutamide and darolutamide that have more potent androgen receptor inhibition).</i>
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