{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:54:07Z","timestamp":1780455247245,"version":"3.54.1"},"reference-count":42,"publisher":"Deutscher Arzte-Verlag GmbH","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"DOI":"10.3238\/arztebl.m2025.0214","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T07:52:31Z","timestamp":1767685951000},"source":"Crossref","is-referenced-by-count":1,"title":["Metamizole: Indications and risks"],"prefix":"10.3238","author":[{"given":"Ingolf","family":"Cascorbi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Baron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"11437","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"10.3238\/arztebl.m2025.0214_ref1","doi-asserted-by":"crossref","unstructured":"Oreskovic Z, Bicanic G, Hrabac P, Tripkovic B, Delimar D: Treatment of postoperative pain after total hip arthroplasty: Comparison between metamizol and paracetamol as adjunctive to opioid analgesics-prospective, double-blind, randomised study. Arch Orthop Trauma Surg 2014; 134: 631\u20136","DOI":"10.1007\/s00402-014-1979-7"},{"key":"10.3238\/arztebl.m2025.0214_ref2","unstructured":"Saray A, Buyukkocak U, Cinel I, Tellioglu AT, Oral U: Diclofenac and metamizol in postoperative analgesia in plastic surgery. Acta Chir Plast 2001; 43: 71\u20136"},{"key":"10.3238\/arztebl.m2025.0214_ref3","doi-asserted-by":"crossref","unstructured":"Schneider T, Mauermann E, Ilgenstein B, Jaquiery C, Ruppen W: Analgesic benefit of metamizole and ibuprofen vs. either medication alone: A randomized clinical trial. Minerva Anestesiol 2022; 88: 448\u201356","DOI":"10.23736\/S0375-9393.22.16346-7"},{"key":"10.3238\/arztebl.m2025.0214_ref4","doi-asserted-by":"crossref","unstructured":"Gaertner J, Stamer UM, Remi C, et al.: Metamizole\/dipyrone for the relief of cancer pain: A systematic review and evidence-based recommendations for clinical practice. Palliat Med 2017; 31: 26\u201334","DOI":"10.1177\/0269216316655746"},{"key":"10.3238\/arztebl.m2025.0214_ref5","unstructured":"BfArM: Rote-Hand-Brief zu metamizolhaltigen Arzneimitteln: Wichtige Ma\u00dfnahmen zur Minimierung der schwerwiegenden Folgen des bekannten Risikos f\u00fcr Agranulozytose. www.bfarm.de\/SharedDocs\/Risikoinformationen\/Pharmakovigilanz\/DE\/RHB\/2024\/rhb-metamizol.html (last accessed on 14 June 2025)."},{"key":"10.3238\/arztebl.m2025.0214_ref6","doi-asserted-by":"crossref","unstructured":"Pierre SC, Schmidt R, Brenneis C, Michaelis M, Geisslinger G, Scholich K: Inhibition of cyclooxygenases by dipyrone. Br J Pharmacol 2007; 151: 494\u2013503","DOI":"10.1038\/sj.bjp.0707239"},{"key":"10.3238\/arztebl.m2025.0214_ref7","doi-asserted-by":"crossref","unstructured":"Cecilio NT, Souza GR, Alves-Filho JC, Cunha FQ, Cunha TM: The PI3K&#947;\/AKT signaling pathway mediates peripheral antinociceptive action of dipyrone. Fundam Clin Pharmacol 2021; 35: 364\u201370","DOI":"10.1111\/fcp.12606"},{"key":"10.3238\/arztebl.m2025.0214_ref8","doi-asserted-by":"crossref","unstructured":"Goncalves Dos Santos G, Vieira WF, Vendramini PH, et al.: Dipyrone is locally hydrolyzed to 4-methylaminoantipyrine and its antihyperalgesic effect depends on CB(2) and kappa-opioid receptors activation. Eur J Pharmacol 2020; 874: 173005","DOI":"10.1016\/j.ejphar.2020.173005"},{"key":"10.3238\/arztebl.m2025.0214_ref9","doi-asserted-by":"crossref","unstructured":"Goncalves Dos Santos G, Li R, Ng MPE, et al.: CB(1) receptor-dependent desensitisation of TRPV1 channels contributes to the analgesic effect of dipyrone in sensitised primary sensory neurons. Br J Pharmacol 2020; 177: 4615\u201326","DOI":"10.1111\/bph.15170"},{"key":"10.3238\/arztebl.m2025.0214_ref10","doi-asserted-by":"crossref","unstructured":"Ludwig WD, M\u00fchlbauer B; Seifert, R.: Arzneimittelverordnungsreport 2023. Berlin: Springer 2024","DOI":"10.1007\/978-3-662-68371-2"},{"key":"10.3238\/arztebl.m2025.0214_ref11","doi-asserted-by":"crossref","unstructured":"Hoffmann F, Bantel C, von Rosen FT, Jobski K: Regional differences in prescribing patterns of metamizole in Germany based on data from 70 million persons. Int J Environ Res Public Health 2020; 17: 3892","DOI":"10.3390\/ijerph17113892"},{"key":"10.3238\/arztebl.m2025.0214_ref12","unstructured":"Grandt D, Lappe, V., Schubert, I.: BARMER Arzneimittelreport 2023 www.barmer.de\/resource\/blob\/1241248\/8e2483171c80ba878809dfdac7ccdb8e\/arzneimittelreport-2023-data.pdf (last accessed on 13 June 2025)."},{"key":"10.3238\/arztebl.m2025.0214_ref13","doi-asserted-by":"crossref","unstructured":"Klose S, Pflock R, Konig IR, Linder R, Schwaninger M: Metamizole and the risk of drug-induced agranulocytosis and neutropenia in statutory health insurance data. Naunyn Schmiedebergs Arch Pharmacol 2020; 393: 681\u201390","DOI":"10.1007\/s00210-019-01774-4"},{"key":"10.3238\/arztebl.m2025.0214_ref14","doi-asserted-by":"crossref","unstructured":"Reist L, Erlenwein J, Meissner W, Stammschulte T, Stuber F, Stamer UM: Dipyrone is the preferred nonopioid analgesic for the treatment of acute and chronic pain. A survey of clinical practice in German-speaking countries. Eur J Pain 2018; 22: 1103\u201312","DOI":"10.1002\/ejp.1194"},{"key":"10.3238\/arztebl.m2025.0214_ref15","doi-asserted-by":"crossref","unstructured":"Jipa M, Isac S, Klimko A, et al.: Opioid-sparing analgesia impacts the perioperative anesthetic management in major abdominal surgery. Medicina (Kaunas) 2022; 58: 487","DOI":"10.3390\/medicina58040487"},{"key":"10.3238\/arztebl.m2025.0214_ref16","doi-asserted-by":"crossref","unstructured":"Tempel G, von Hundelshausen B, Reeker W: The opiate-sparing effect of dipyrone in post-operative pain therapy with morphine using a patient-controlled analgesic system. Intensive Care Med 1996; 22: 1043\u20137","DOI":"10.1007\/BF01699225"},{"key":"10.3238\/arztebl.m2025.0214_ref17","doi-asserted-by":"crossref","unstructured":"Peiro AM, Martinez J, Martinez E, et al.: Efficacy and tolerance of metamizole versus morphine for acute pancreatitis pain. Pancreatology 2008; 8: 25\u20139","DOI":"10.1159\/000114852"},{"key":"10.3238\/arztebl.m2025.0214_ref18","doi-asserted-by":"crossref","unstructured":"Stessel B, Boon M, Pelckmans C, et al.: Metamizole vs. ibuprofen at home after day case surgery: A double-blind randomised controlled noninferiority trial. Eur J Anaesthesiol 2019; 36: 351\u20139","DOI":"10.1097\/EJA.0000000000000972"},{"key":"10.3238\/arztebl.m2025.0214_ref19","unstructured":"Abdulla S, Eckhardt R, Netter U, Abdulla W: A randomized, double-blind, controlled trial on non-opioid analgesics and opioid consumption for postoperative pain relief after laparoscopic cholecystectomy. Acta Anaesthesiol Belg 2012; 63: 43\u201350"},{"key":"10.3238\/arztebl.m2025.0214_ref20","doi-asserted-by":"crossref","unstructured":"Ohnesorge H, Bein B, Hanss R, et al.: Paracetamol versus metamizol in the treatment of postoperative pain after breast surgery: A randomized, controlled trial. Eur J Anaesthesiol 2009; 26: 648\u201353","DOI":"10.1097\/EJA.0b013e328329b0fd"},{"key":"10.3238\/arztebl.m2025.0214_ref21","doi-asserted-by":"crossref","unstructured":"Soliman N, Moisset X, Ferraro MC, et al.: Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: A systematic review and meta-analysis. Lancet Neurol 2025; 24: 413\u201328","DOI":"10.1016\/S1474-4422(25)00068-7"},{"key":"10.3238\/arztebl.m2025.0214_ref22","unstructured":"Fachinformation Metamizol AbZ 500 mg Tabletten. www.fachinfo.de\/fi\/pdf\/013816\/metamizol-abz-500-mg-tabletten (last accessed on 13 June 2025)."},{"key":"10.3238\/arztebl.m2025.0214_ref23","unstructured":"EMA: European database of suspected adverse drug reactions reports www.adrreports.eu."},{"key":"10.3238\/arztebl.m2025.0214_ref24","doi-asserted-by":"crossref","unstructured":"Sabate M, Ibanez L, Perez E, et al.: Risk of acute liver injury associated with the use of drugs: A multicentre population survey. Aliment Pharmacol Ther 2007; 25: 1401\u20139","DOI":"10.1111\/j.1365-2036.2007.03338.x"},{"key":"10.3238\/arztebl.m2025.0214_ref25","doi-asserted-by":"crossref","unstructured":"Lutz M: Metamizole (Dipyrone) and the liver: A review of the literature. J Clin Pharmacol 2019; 59: 1433\u201342","DOI":"10.1002\/jcph.1512"},{"key":"10.3238\/arztebl.m2025.0214_ref26","doi-asserted-by":"crossref","unstructured":"Hedenmalm K, Pacurariu A, Slattery J, Kurz X, Candore G, Flynn R: Is there an increased risk of hepatotoxicity with Metamizole? A comparative cohort study in incident users. Drug Saf 2021; 44: 973\u201385","DOI":"10.1007\/s40264-021-01087-7"},{"key":"10.3238\/arztebl.m2025.0214_ref27","unstructured":"BfArM: Rote-Hand-Brief zu Metamizol: Risiko f\u00fcr arzneimittelbedingten Leberschaden. www.bfarm.de\/SharedDocs\/Risikoinformationen\/Pharmakovigilanz\/DE\/RHB\/2020\/rhb-metamizol.html (last accessed on 14 June 2025)."},{"key":"10.3238\/arztebl.m2025.0214_ref28","doi-asserted-by":"crossref","unstructured":"Sebode M, Reike-Kunze M, Weidemann S, et al.: Metamizole: An underrated agent causing severe idiosyncratic drug-induced liver injury. Br J Clin Pharmacol 2020; 86: 1406\u201315","DOI":"10.1111\/bcp.14254"},{"key":"10.3238\/arztebl.m2025.0214_ref29","doi-asserted-by":"crossref","unstructured":"Hoffmann F, Bantel C, Jobski K: Agranulocytosis attributed to metamizole: An analysis of spontaneous reports in EudraVigilance 1985\u20132017. Basic Clin Pharmacol Toxicol 2020; 126: 116\u201325","DOI":"10.1111\/bcpt.13310"},{"key":"10.3238\/arztebl.m2025.0214_ref30","doi-asserted-by":"crossref","unstructured":"Andrade S, Bartels DB, Lange R, Sandford L, Gurwitz J: Safety of metamizole: A systematic review of the literature. J Clin Pharm Ther 2016; 41: 459\u201377","DOI":"10.1111\/jcpt.12422"},{"key":"10.3238\/arztebl.m2025.0214_ref31","doi-asserted-by":"crossref","unstructured":"Backstrom M, Hagg S, Mjorndal T, Dahlqvist R: Utilization pattern of metamizole in northern Sweden and risk estimates of agranulocytosis. Pharmacoepidemiol Drug Saf 2002; 11: 239\u201345","DOI":"10.1002\/pds.697"},{"key":"10.3238\/arztebl.m2025.0214_ref32","doi-asserted-by":"crossref","unstructured":"Macia-Martinez MA, Castillo-Cano B, Garcia-Poza P, Martin-Merino E: Risk of agranulocytosis with metamizole in comparison with alternative medications based on health records in Spain. Eur J Clin Pharmacol 2024; 80: 1503\u201314","DOI":"10.1007\/s00228-024-03706-5"},{"key":"10.3238\/arztebl.m2025.0214_ref33","unstructured":"EMA: Measures to minimise serious outcomes of known side effect with painkiller metamizole. www.ema.europa.eu\/en\/documents\/referral\/metamizole-containing-medicinal-products-article-107i-referral-measures-minimise-serious-outcomes-known-side-effect-painkiller-metamizole_en.pdf (last accessed on 14 June 2025)."},{"key":"10.3238\/arztebl.m2025.0214_ref34","doi-asserted-by":"crossref","unstructured":"Goldstein JI, Jarskog LF, Hilliard C, et al.: Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles. Nat Commun 2014; 5: 4757","DOI":"10.1038\/ncomms5757"},{"key":"10.3238\/arztebl.m2025.0214_ref35","doi-asserted-by":"crossref","unstructured":"Cismaru AL, Rudin D, Ibanez L, et al.: Genome-wide association study of Metamizole-induced agranulocytosis in European populations. Genes (Basel) 2020; 11: 1275","DOI":"10.3390\/genes11111275"},{"key":"10.3238\/arztebl.m2025.0214_ref36","doi-asserted-by":"crossref","unstructured":"Caraco Y, Zylber-Katz E, Fridlander M, Admon D, Levy M: The effect of short-term dipyrone administration on cyclosporin pharmacokinetics. Eur J Clin Pharmacol 1999; 55: 475\u20138","DOI":"10.1007\/s002280050659"},{"key":"10.3238\/arztebl.m2025.0214_ref37","doi-asserted-by":"crossref","unstructured":"Bachmann F, Duthaler U, Meyer Zu Schwabedissen HE, et al.: Metamizole is a moderate cytochrome P450 inducer via the constitutive androstane receptor and a weak inhibitor of CYP1A2. Clin Pharmacol Ther 2021; 109: 1505\u201316","DOI":"10.1002\/cpt.2141"},{"key":"10.3238\/arztebl.m2025.0214_ref38","doi-asserted-by":"crossref","unstructured":"Watermeyer F, Gaebler AJ, Neuner I, et al.: Discovering interactions in polypharmacy: Impact of metamizole on the metabolism of quetiapine. Br J Clin Pharmacol 2024; 90: 2793\u2013801","DOI":"10.1111\/bcp.16168"},{"key":"10.3238\/arztebl.m2025.0214_ref39","unstructured":"FDA: Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. www.fda.gov\/drugs\/drug-interactions-labeling\/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers."},{"key":"10.3238\/arztebl.m2025.0214_ref40","doi-asserted-by":"crossref","unstructured":"Dannenberg L, Petzold T, Achilles A, et al.: Dose reduction, oral application, and order of intake to preserve aspirin antiplatelet effects in dipyrone co-medicated chronic artery disease patients. Eur J Clin Pharmacol 2019; 75: 13\u201320","DOI":"10.1007\/s00228-018-2560-z"},{"key":"10.3238\/arztebl.m2025.0214_ref41","doi-asserted-by":"crossref","unstructured":"Eleuterio OHP, Veronezi RN, Martinez-Sobalvarro JV, et al.: Safety of metamizole (dipyrone) for the treatment of mild to moderate pain-an overview of systematic reviews. Naunyn Schmiedebergs Arch Pharmacol 2024; 397: 8515\u201325","DOI":"10.1007\/s00210-024-03240-2"},{"key":"10.3238\/arztebl.m2025.0214_ref42","doi-asserted-by":"crossref","unstructured":"Stammschulte T, Ludwig WD, Muhlbauer B, Bronder E, Gundert-Remy U: Metamizole (dipyrone)-associated agranulocytosis. An analysis of German spontaneous reports 1990\u20132012. Eur J Clin Pharmacol 2015; 71: 1129\u201338","DOI":"10.1007\/s00228-015-1895-y"}],"container-title":["Deutsches \u00c4rzteblatt international"],"original-title":[],"link":[{"URL":"https:\/\/www.aerzteblatt.de\/10.3238\/arztebl.m2025.0214","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T07:53:34Z","timestamp":1767686014000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.aerzteblatt.de\/10.3238\/arztebl.m2025.0214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":42,"URL":"https:\/\/doi.org\/10.3238\/arztebl.m2025.0214","relation":{},"ISSN":["1866-0452"],"issn-type":[{"value":"1866-0452","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]}}}