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leflunomide and Acute Liver Injury, Drug-Induced

leflunomide has been researched along with Acute Liver Injury, Drug-Induced in 35 studies

Leflunomide: An isoxazole derivative that inhibits dihydroorotate dehydrogenase, the fourth enzyme in the pyrimidine biosynthetic pathway. It is used an immunosuppressive agent in the treatment of RHEUMATOID ARTHRITIS and PSORIATIC ARTHRITIS.
leflunomide : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-methyl-1,2-oxazole-4-carboxylic acid with the anilino group of 4-(trifluoromethyl)aniline. The prodrug of teriflunomide.

Research Excerpts

ExcerptRelevanceReference
" Methotrexate (MTX) and Leflunomide (LEF) combination has a better efficacy in the treatment of active rheumatoid arthritis (RA), but hepatotoxicity was observed."9.20Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis. ( Chen, Z; Li, XM; Li, XP; Li, ZG; Su, Y; Xiang, N; Yang, M; Zhang, MJ; Zhao, DB; Zhu, P; Zuo, XX, 2015)
" In patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA), the incidence of elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) enzymes associated with methotrexate (MTX), leflunomide (LEF) and MTX+LEF versus other DMARDs was examined."7.76Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leflunomide. ( Beukelman, T; Cassell, S; Curtis, JR; Greenberg, JD; Kavanaugh, A; Kremer, JM; Onofrei, A; Reed, G; Strand, V, 2010)
" Methotrexate (MTX) and Leflunomide (LEF) combination has a better efficacy in the treatment of active rheumatoid arthritis (RA), but hepatotoxicity was observed."5.20Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis. ( Chen, Z; Li, XM; Li, XP; Li, ZG; Su, Y; Xiang, N; Yang, M; Zhang, MJ; Zhao, DB; Zhu, P; Zuo, XX, 2015)
"A 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate for 8 years and on leflunomide for 6 years was admitted for weakness, edema, ascites, and petechiae of the lower legs."3.96Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report. ( Girndt, M; Lübbert, C; Pliquett, RU; Schäfer, C, 2020)
" In patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA), the incidence of elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) enzymes associated with methotrexate (MTX), leflunomide (LEF) and MTX+LEF versus other DMARDs was examined."3.76Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leflunomide. ( Beukelman, T; Cassell, S; Curtis, JR; Greenberg, JD; Kavanaugh, A; Kremer, JM; Onofrei, A; Reed, G; Strand, V, 2010)
"Leflunomide, a new immunomodulatory agent, was prescribed to a 67-year-old female patient with rheumatoid arthritis."3.72Leflunomide-induced acute hepatitis. ( Agúndez, JA; Díaz-Rubio, M; Fernández-Gutiérrez, B; Ladero, JM; Ortega, L; Sevilla-Mantilla, C, 2004)
"Spontaneous cases of hepatic adverse events have been reported in patients with rheumatoid arthritis who were being treated with leflunomide, one of the newer disease-modifying antirheumatic drugs (DMARDs)."3.72Newer disease-modifying antirheumatic drugs and the risk of serious hepatic adverse events in patients with rheumatoid arthritis. ( Bitton, A; Ernst, P; Hudson, M; Kezouh, A; Suissa, S, 2004)
"Leflunomide is a disease modifying anti-rheumatic drug (DMARD) beneficial in refractory cases of rheumatoid arthritis."1.51Leflunomide-induced liver injury in mice: Involvement of TLR4 mediated activation of PI3K/mTOR/NFκB pathway. ( El-Ghaiesh, SH; Elshaer, RE; Elsherbiny, NM; Nosseir, N; Tawfik, MK; Toraih, EA; Zaitone, SA, 2019)
"Leflunomide is an immunosuppressive agent marketed as a disease-modifying antirheumatic drug."1.43Inhibition of hepatic cytochrome P450 enzymes and sodium/bile acid cotransporter exacerbates leflunomide-induced hepatotoxicity. ( Cao, YY; Chen, C; Lin, YF; Luan, Y; Ma, LL; Ni, X; Pan, GY; Wang, J; Wang, L; Wu, ZT; Zhang, XF, 2016)
" We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts."1.37FDA-approved drug labeling for the study of drug-induced liver injury. ( Chen, M; Fang, H; Liu, Z; Shi, Q; Tong, W; Vijay, V, 2011)
" An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems."1.36Developing structure-activity relationships for the prediction of hepatotoxicity. ( Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ, 2010)
"Leflunomide has high hepatotoxic potential, especially when combined with methotrexate."1.36[Hepatotoxicity induced by new immunosuppressants]. ( Andrade, RJ; Cotta, J; Lucena, MA; Robles, M; Toscano, E, 2010)
"Acetaminophen (APAP) is safe at therapeutic levels but causes liver injury via N-acetyl-p-benzoquinone imine (NAPQI)-induced oxidative stress when overdose."1.35Prevention of acetaminophen (APAP)-induced hepatotoxicity by leflunomide via inhibition of APAP biotransformation to N-acetyl-p-benzoquinone imine. ( Chan, EC; New, LS; Tan, SC, 2008)
"Following repeated liver biopsy, autoimmune hepatitis was assumed and prednisolone and azathioprine were initiated."1.35[Elevated liver enzymes in rheumatoid arthritis : differential diagnostic considerations based on a case report]. ( Hartmann, U; Reuss-Borst, M; Schmitt, S, 2008)
"Leflunomide is a novel disease modifying antirheumatic drug (DMARD)."1.32Leflunomide for the treatment of rheumatoid arthritis in clinical practice: incidence and severity of hepatotoxicity. ( Brouwers, JR; Houtman, NM; Jansen, TL; Spoelstra, P; van Roon, EN, 2004)

Research

Studies (35)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's10 (28.57)29.6817
2010's21 (60.00)24.3611
2020's4 (11.43)2.80

Authors

AuthorsStudies
Fourches, D1
Barnes, JC1
Day, NC1
Bradley, P1
Reed, JZ1
Tropsha, A1
Greene, N1
Fisk, L1
Naven, RT1
Note, RR1
Patel, ML1
Pelletier, DJ1
Ekins, S1
Williams, AJ1
Xu, JJ1
Chen, M2
Vijay, V1
Shi, Q2
Liu, Z2
Fang, H2
Tong, W3
Dawson, S1
Stahl, S2
Paul, N1
Barber, J1
Kenna, JG2
Ding, D1
Kelly, R1
Warner, DJ1
Chen, H1
Cantin, LD1
Walker, CL1
Noeske, T1
Morgan, RE1
van Staden, CJ1
Chen, Y1
Kalyanaraman, N1
Kalanzi, J1
Dunn, RT1
Afshari, CA1
Hamadeh, HK1
Suzuki, A1
Thakkar, S1
Yu, K1
Hu, C1
Devarbhavi, H1
Ghabril, M1
Barnhart, H1
Patil, M1
Raj, S1
Gu, J1
Chalasani, N1
Bonkovsky, HL1
Sokar, SS1
Alkabbani, MA1
Akool, ES1
Abu-Risha, SE1
Elshaer, RE1
Tawfik, MK1
Nosseir, N1
El-Ghaiesh, SH2
Toraih, EA1
Elsherbiny, NM1
Zaitone, SA2
Pliquett, RU1
Lübbert, C1
Schäfer, C1
Girndt, M1
Alamri, RD1
Elmeligy, MA1
Albalawi, GA1
Alquayr, SM1
Alsubhi, SS1
Xuan, J1
Ren, Z1
Qing, T1
Couch, L1
Shi, L1
Tolleson, WH1
Guo, L1
Huang, RY1
Pan, HD1
Wu, JQ1
Zhou, H1
Li, ZG2
Qiu, P1
Zhou, YY1
Chen, XM1
Xie, ZX1
Xiao, Y1
Huang, QC1
Liu, L1
Bilasy, SE1
Essawy, SS1
Mandour, MF1
Ali, EA1
Lin, KM1
Cheng, TT1
Lin, JC1
Chen, CJ1
Xiang, N1
Li, XM1
Zhang, MJ1
Zhao, DB1
Zhu, P1
Zuo, XX1
Yang, M1
Su, Y1
Chen, Z1
Li, XP1
Ma, LL1
Wu, ZT1
Wang, L1
Zhang, XF1
Wang, J1
Chen, C1
Ni, X1
Lin, YF1
Cao, YY1
Luan, Y1
Pan, GY1
Goda, K1
Takahashi, T1
Kobayashi, A1
Shoda, T1
Kuno, H1
Sugai, S1
Tan, SC1
New, LS1
Chan, EC1
Curtis, JR1
Beukelman, T1
Onofrei, A1
Cassell, S1
Greenberg, JD1
Kavanaugh, A1
Reed, G1
Strand, V1
Kremer, JM1
Toscano, E1
Cotta, J1
Robles, M1
Lucena, MA1
Andrade, RJ1
Gupta, R2
Bhatia, J1
Gupta, SK2
Perdan-Pirkmajer, K1
Hočevar, A1
Rotar, Ž1
Žibert, J1
Marolt, VF1
Gučev, F1
Tomšič, M1
Grove, ML1
Yao, HW1
Jin, Y1
Li, J1
Zhang, YF1
Li, CY1
Xu, SY1
Sevilla-Mantilla, C1
Ortega, L1
Agúndez, JA1
Fernández-Gutiérrez, B1
Ladero, JM1
Díaz-Rubio, M1
van Roon, EN1
Jansen, TL1
Houtman, NM1
Spoelstra, P1
Brouwers, JR1
Suissa, S1
Ernst, P1
Hudson, M1
Bitton, A1
Kezouh, A1
Suzuki, Y1
Saito, E1
Wakabayashi, T1
Suwa, A1
Hartmann, U1
Schmitt, S1
Reuss-Borst, M1
Breedveld, FC1

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Multi-Center, Longitudinal Study of Drug-and CAM-Induced Liver Injury[NCT00345930]4,000 participants (Anticipated)Observational2004-09-30Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Reviews

3 reviews available for leflunomide and Acute Liver Injury, Drug-Induced

ArticleYear
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
    Drug discovery today, 2016, Volume: 21, Issue:4

    Topics: Chemical and Drug Induced Liver Injury; Databases, Factual; Drug Labeling; Humans; Pharmaceutical Pr

2016
Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induced liver injury: A comprehensive review.
    International immunopharmacology, 2021, Volume: 93

    Topics: Antineoplastic Agents; Antiviral Agents; Chemical and Drug Induced Liver Injury; Clinical Trials as

2021
[Adverse effects of conventional DMARDs and biologic DMARDs].
    Nihon rinsho. Japanese journal of clinical medicine, 2007, Oct-28, Volume: 65 Suppl 8

    Topics: Antibodies, Monoclonal; Antirheumatic Agents; Chemical and Drug Induced Liver Injury; Cysteine; Drug

2007

Trials

3 trials available for leflunomide and Acute Liver Injury, Drug-Induced

ArticleYear
Comparison of combination therapy with methotrexate and sinomenine or leflunomide for active rheumatoid arthritis: A randomized controlled clinical trial.
    Phytomedicine : international journal of phytotherapy and phytopharmacology, 2019, Volume: 57

    Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Chemical and Drug Induced Liver Injury; Drug The

2019
Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis.
    International immunopharmacology, 2015, Volume: 28, Issue:1

    Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Chemical and Drug Induced

2015
Risk of hepatotoxicity with add-on leflunomide in rheumatoid arthritis patients.
    Arzneimittel-Forschung, 2011, Volume: 61, Issue:5

    Topics: Adult; Aged; Alanine Transaminase; Antirheumatic Agents; Arthritis, Rheumatoid; Aspartate Aminotrans

2011

Other Studies

29 other studies available for leflunomide and Acute Liver Injury, Drug-Induced

ArticleYear
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
    Chemical research in toxicology, 2010, Volume: 23, Issue:1

    Topics: Animals; Chemical and Drug Induced Liver Injury; Cluster Analysis; Databases, Factual; Humans; MEDLI

2010
Developing structure-activity relationships for the prediction of hepatotoxicity.
    Chemical research in toxicology, 2010, Jul-19, Volume: 23, Issue:7

    Topics: Chemical and Drug Induced Liver Injury; Databases, Factual; Humans; Structure-Activity Relationship;

2010
A predictive ligand-based Bayesian model for human drug-induced liver injury.
    Drug metabolism and disposition: the biological fate of chemicals, 2010, Volume: 38, Issue:12

    Topics: Bayes Theorem; Chemical and Drug Induced Liver Injury; Humans; Ligands

2010
FDA-approved drug labeling for the study of drug-induced liver injury.
    Drug discovery today, 2011, Volume: 16, Issue:15-16

    Topics: Animals; Benchmarking; Biomarkers, Pharmacological; Chemical and Drug Induced Liver Injury; Drug Des

2011
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.
    Drug metabolism and disposition: the biological fate of chemicals, 2012, Volume: 40, Issue:1

    Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters

2012
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
    PLoS computational biology, 2011, Volume: 7, Issue:12

    Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Chemical and Drug Induced Liver Injury; Da

2011
Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.
    Drug metabolism and disposition: the biological fate of chemicals, 2012, Volume: 40, Issue:12

    Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters

2012
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
    Toxicological sciences : an official journal of the Society of Toxicology, 2013, Volume: 136, Issue:1

    Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily

2013
Leflunomide-induced liver injury: Differences in characteristics and outcomes in Indian and US registries.
    Liver international : official journal of the International Association for the Study of the Liver, 2022, Volume: 42, Issue:6

    Topics: Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic; Drug-Relate

2022
Hepatoprotective effects of carvedilol and crocin against leflunomide-induced liver injury.
    International immunopharmacology, 2022, Volume: 113, Issue:Pt A

    Topics: Animals; Carvedilol; Catalase; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liv

2022
Leflunomide-induced liver injury in mice: Involvement of TLR4 mediated activation of PI3K/mTOR/NFκB pathway.
    Life sciences, 2019, Oct-15, Volume: 235

    Topics: Animals; Caspase 3; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Leflun

2019
Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report.
    Journal of medical case reports, 2020, Feb-05, Volume: 14, Issue:1

    Topics: Arthritis, Rheumatoid; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Female; Hu

2020
Mitochondrial dysfunction induced by leflunomide and its active metabolite.
    Toxicology, 2018, 03-01, Volume: 396-397

    Topics: Adenosine Triphosphate; Anti-Inflammatory Agents, Non-Steroidal; Bongkrekic Acid; Chemical and Drug

2018
Myelosuppressive and hepatotoxic potential of leflunomide and methotrexate combination in a rat model of rheumatoid arthritis.
    Pharmacological reports : PR, 2015, Volume: 67, Issue:1

    Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Blood

2015
Tumor necrosis factor-α antagonist therapy for concomitant rheumatoid arthritis and hepatitis C virus infection: a case series study.
    Clinical rheumatology, 2015, Volume: 34, Issue:6

    Topics: Adalimumab; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumato

2015
Inhibition of hepatic cytochrome P450 enzymes and sodium/bile acid cotransporter exacerbates leflunomide-induced hepatotoxicity.
    Acta pharmacologica Sinica, 2016, Volume: 37, Issue:3

    Topics: Animals; Antirheumatic Agents; Cells, Cultured; Chemical and Drug Induced Liver Injury; Crotonates;

2016
Usefulness of in vitro combination assays of mitochondrial dysfunction and apoptosis for the estimation of potential risk of idiosyncratic drug induced liver injury.
    The Journal of toxicological sciences, 2016, Volume: 41, Issue:5

    Topics: Acetaminophen; Apoptosis; Biological Assay; Biomarkers; Caspase 3; Caspase 7; Cells, Cultured; Chemi

2016
Prevention of acetaminophen (APAP)-induced hepatotoxicity by leflunomide via inhibition of APAP biotransformation to N-acetyl-p-benzoquinone imine.
    Toxicology letters, 2008, Aug-28, Volume: 180, Issue:3

    Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Antirheumatic Agents; Benzoquinones; Biotransforma

2008
Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leflunomide.
    Annals of the rheumatic diseases, 2010, Volume: 69, Issue:1

    Topics: Adolescent; Adult; Aged; Alanine Transaminase; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis

2010
[Hepatotoxicity induced by new immunosuppressants].
    Gastroenterologia y hepatologia, 2010, Volume: 33, Issue:1

    Topics: Azathioprine; Chemical and Drug Induced Liver Injury; Cyclosporine; Humans; Immunosuppressive Agents

2010
Tumour necrosis factor-alpha inhibitor-induced hepatic injury in patients with rheumatoid arthritis: two case reports and an analysis of the laboratory data from the Slovenian national biologicals registry.
    Rheumatology international, 2013, Volume: 33, Issue:11

    Topics: Adalimumab; Adult; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; B

2013
US Food and Drug Administration gets it right.
    BMJ (Clinical research ed.), 2002, Oct-05, Volume: 325, Issue:7367

    Topics: Cardiovascular Diseases; Chemical and Drug Induced Liver Injury; Cyclooxygenase 2; Drug Approval; Hu

2002
[Effects of leflunomide on immunological liver injury].
    Yao xue xue bao = Acta pharmaceutica Sinica, 2001, Volume: 36, Issue:10

    Topics: Adjuvants, Immunologic; Animals; Cell Division; Chemical and Drug Induced Liver Injury; Interleukin-

2001
Leflunomide-induced acute hepatitis.
    Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2004, Volume: 36, Issue:1

    Topics: Adjuvants, Immunologic; Aged; Anion Exchange Resins; Arthritis, Rheumatoid; Chemical and Drug Induce

2004
Leflunomide for the treatment of rheumatoid arthritis in clinical practice: incidence and severity of hepatotoxicity.
    Drug safety, 2004, Volume: 27, Issue:5

    Topics: Adult; Aged; Aged, 80 and over; Antirheumatic Agents; Chemical and Drug Induced Liver Injury; Female

2004
Newer disease-modifying antirheumatic drugs and the risk of serious hepatic adverse events in patients with rheumatoid arthritis.
    The American journal of medicine, 2004, Jul-15, Volume: 117, Issue:2

    Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; C

2004
Severe hepatotoxicity in a rheumatoid arthritis patient switched from leflunomide to methotrexate.
    MedGenMed : Medscape general medicine, 2005, Sep-06, Volume: 7, Issue:3

    Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Chemical and Drug Induced Liver Injury; Female;

2005
[Elevated liver enzymes in rheumatoid arthritis : differential diagnostic considerations based on a case report].
    Zeitschrift fur Rheumatologie, 2008, Volume: 67, Issue:5

    Topics: Adalimumab; Adolescent; Alanine Transaminase; Antibodies, Monoclonal; Antibodies, Monoclonal, Humani

2008
Is there a place for leflunomide in the treatment of rheumatoid arthritis?
    Lancet (London, England), 2001, Oct-13, Volume: 358, Issue:9289

    Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Chemical and Drug Induced Liver Inju

2001