preprints.org > medicine and pharmacology > medicine and pharmacology > doi: 10.20944/preprints202402.0658.v1

Preprint Case Report Version 1 Preserved in Portico This version is not peer-reviewed

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)

Objective: We report the case of a patient who developed acute pancytopenia and mixed-pattern liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old female patient with chronic systemic idiopathic erosive arthritis was admitted for conservative treatment with analgesia and physiotherapy for a pelvic ring fracture. Due to the arthritis, she received treatment with MTX 15 mg/week, hydroxychloroquine 200 mg/day and prednisone 7.5 mg/day. On admission, she had no infectious, hematologic or oncologic diseases. She received analgesic therapy with metamizole 4000 mg/day and oxycodone/naloxone 30/15 mg/day. After hospital admission, she received MTX 15 mg as planned in addition to esomeprazole 80 mg/day and torasemide 10 mg/day. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. This condition persisted and worsened during the first two weeks of hospitalization. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures and an exacerbation of pre-existing mouth ulcers. Further investigations were unable to determine a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate 7.5 mg 4 times/day was administered. After an expert pharmacological evaluation, the concomitant administration of metamizole and esomeprazole was discontinued, after which the blood counts and liver parameters normalized. Discussion: After MTX administration, a new onset leukopenia (2.34 G/L), thrombocytopenia (46 G/L), worsened anemia (83 g/L) and elevated liver enzymes were detected. Presumably, a methotrexate-induced bone marrow suppression was already in progress. 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, proton pump inhibitors, and loop diuretics necessitates that healthcare providers consider drug-drug interactions as potential causes of acute hematotoxicity and hepatotoxicity 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 and closely monitor laboratory parameters to preempt any adverse drug reactions.

pharmacokinetic-pharmacodynamic interactions; low-dose methotrexate; proton pump inhibitors; analgesics; pancytopenia; hepatotoxicity

Medicine and Pharmacology, Medicine and Pharmacology

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