Case Report
Version 2
Preserved in Portico This version is not peer-reviewed
Acute Methotrexate Toxicity under Low Dose Therapy
Version 1
: Received: 9 February 2024 / Approved: 12 February 2024 / Online: 12 February 2024 (10:25:33 CET)
Version 2 : Received: 20 February 2024 / Approved: 20 February 2024 / Online: 21 February 2024 (09:30:30 CET)
Version 3 : Received: 29 March 2024 / Approved: 29 March 2024 / Online: 1 April 2024 (11:53:15 CEST)
Version 2 : Received: 20 February 2024 / Approved: 20 February 2024 / Online: 21 February 2024 (09:30:30 CET)
Version 3 : Received: 29 March 2024 / Approved: 29 March 2024 / Online: 1 April 2024 (11:53:15 CEST)
How to cite: Duwor, S.; Aboe, M.; Mensah, D. Acute Methotrexate Toxicity under Low Dose Therapy. Preprints 2024, 2024020658. https://doi.org/10.20944/preprints202402.0658.v2 Duwor, S.; Aboe, M.; Mensah, D. Acute Methotrexate Toxicity under Low Dose Therapy. Preprints 2024, 2024020658. https://doi.org/10.20944/preprints202402.0658.v2
Abstract
Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes, consider dose adjustment of relevant concomitant medications.
Keywords
pharmacokinetic-pharmacodynamic interactions; low-dose methotrexate; proton pump inhibitors; analgesics; pancytopenia; hepatotoxicity
Subject
Medicine and Pharmacology, Medicine and Pharmacology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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