BETWEEN EFFICACY AND RISK: A CRITICAL APPRAISAL OF METAMIZOLE’S PHARMACOLOGY, CLINICAL USE AND REGULATORY STATUS
Abstract
This review critically assesses metamizole's pharmacology, clinical efficacy, and safety profile, with particular focus on its widespread over-the-counter (OTC) availability in Poland versus more restrictive approaches elsewhere. The primary research objective was to evaluate whether the clinical benefits of metamizole outweigh its well-documented risks, especially severe adverse effects such as agranulocytosis and immune-mediated liver injury. During the research PubMed, Google Scholar, and institutional sources were used, applying keywords: “pyralgin,” “metamizole,” “analgesic,” “side effects,” “synergy,” and “combination”. Publications from 2000 to 2025 were screened for relevance, with a primary focus on articles in English and Polish. Abstracts were initially analyzed, followed by full-text review; 20 pertinent sources were ultimately selected for appraisal, comparing indications, mechanisms, and interactions with other analgesics, notably paracetamol, NSAIDs, opioids, and gabapentin. Findings demonstrate that metamizole shows unique spasmolytic, analgesic, and antipyretic properties, and offers therapeutic synergism with various analgesic combinations, aiding multimodal pain management when minimizing opioid or NSAID use is preferred. However, serious adverse events, while infrequent, are potentially fatal and unpredictable, with no effective preventive measures or reliable individual risk prediction identified. The review concludes that the unrestricted OTC availability and mass media promotion of metamizole pose disproportionate public health risks. It recommends limiting access to prescription-only status and ending promotional advertising for common ailments, given the availability of safer first-line analgesics.
References
Sznejder, H., Amand, C., Stewart, A., Salazar, R., & Scala, W. A. R. (2022). Real world evidence of the use of metamizole (dipyrone) by the Brazilian population: A retrospective cohort with over 380,000 patients. Einstein (São Paulo, Brazil), 20, eAO6353. https://doi.org/10.31744/einstein_journal/2022AO6353
National Institute of Diabetes and Digestive and Kidney Diseases. (2012–). LiverTox: Clinical and research information on drug-induced liver injury [Internet]. Metamizole [Dipyrone] (updated 2024, June 2). Bethesda, MD: U.S. National Library of Medicine. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK604194/
Poradowski, D., Chrószcz, A., Spychaj, R., Wolińska, J., & Onar, V. (2024). Influence of metamizole on antitumour activity of risedronate sodium in in vitro studies on canine (D-17) and human (U-2 OS) osteosarcoma cell lines. Biomedicines, 12(8), 1869. https://doi.org/10.3390/biomedicines12081869
Pyznar, O., Mól, N., Zasada, M., Zasada, W., Mazurek, M., & Kwinta, P. (2021). Over-the-counter antipyretics use among children from Southeastern Poland. Journal of Mother and Child, 25(1), 35–43. https://doi.org/10.34763/jmotherandchild.20212501.d-20-00024
Malheiro, L., Viana, A., Nascimento, J., Apolonio, J., Júnior, R., & Silva, K. (2023). One hundred years of dipyrone (metamizole): The recent evidence on its safety. Peer Review, 5, 89–122. https://doi.org/10.53660/380.prw1407
European Medicines Agency. (2024, September 6). EMA recommends measures to minimise serious outcomes of known side effect with painkiller metamizole. Retrieved from https://www.ema.europa.eu/en/documents/referral/metamizole-containing-medicinal-products-article-107i-referral-ema-recommends-measures-minimise-serious-outcomes-known-side-effect-painkiller-metamizole_en.pdf
Topuz, R. D., Gündüz, Ö., Karadağ, Ç. H., & Ulugöl, A. (2020). Non-opioid analgesics and the endocannabinoid system. Balkan Medical Journal, 37(6), 309–315. https://doi.org/10.4274/balkanmedj.galenos.2020.2020.6.66
Misiołek, H., Zajączkowska, R., Daszkiewicz, A., Woroń, J., Dobrogowski, J., & Wordliczek, J., et al. (2018). Postoperative pain management—2018 consensus statement of the Section of Regional Anaesthesia and Pain Therapy of the Polish Society of Anaesthesiology and Intensive Therapy, the Polish Society of Regional Anaesthesia and Pain Therapy, the Polish Association for the Study of Pain and the National Consultant in Anaesthesiology and Intensive Therapy. Anaesthesiology Intensive Therapy, 50(3).
SUN-FARM Sp. z o.o. (2020). Metamizol-SF, 500 mg/ml, roztwór do wstrzykiwań: Charakterystyka produktu leczniczego. Retrieved from https://rejestry.ezdrowie.gov.pl/api/rpl/medicinal-products/42945/characteristic
National Institute of Child Health and Human Development. (2006–). Drugs and Lactation Database (LactMed®) [Internet]. Dipyrone. Bethesda, MD: U.S. National Library of Medicine. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK501526/
Brinkman, D. J., Hendriksen, L. C., Rigter, I. M., & Hollmann, M. W. (2025). Pharmacology and relevant drug interactions of metamizole. British Journal of Clinical Pharmacology, 91(7), 2095–2102. https://doi.org/10.1002/bcp.70101
López-Muñoz, F. J., Godínez-Chaparro, B., Huerta-Cruz, J. C., Guevara-López, U., Domínguez-Ramírez, A. M., & Cortés-Arroyo, A. R. (2008). The antinociceptive efficacy of morphine, metamizol, or their combination in an experimental rat model with different levels of inflammatory pain. Pharmacology, Biochemistry, and Behavior, 91(1), 196–201. https://doi.org/10.1016/j.pbb.2008.07.007
Krzyżak-Jankowicz, M., & Jankowicz, R. (2015). Metamizole and paracetamol—Similar but not the same drugs. Medycyna Paliatywna w Praktyce, 9(2), 59–65.
Wordliczek, J., Zajączkowska, R., Dziki, A., Jackowski, M., Richter, P., Woroń, J., Misiołek, H., Dobrogowski, J., Paśnik, K., Wallner, G., & Malec-Milewska, M. (2019). Postoperative pain relief in general surgery: Recommendations of the Association of Polish Surgeons, Polish Society of Anaesthesiology and Intensive Therapy, Polish Association for the Study of Pain and Polish Association of Regional Anaesthesia and Pain Treatment. Polski Przegląd Chirurgiczny, 91(1), 47–68. https://doi.org/10.5604/01.3001.0013.1088
Montes, A., Warner, W., & Puig, M. M. (2000). Use of intravenous patient-controlled analgesia for the documentation of synergy between tramadol and metamizol. British Journal of Anaesthesia, 85(2), 217–223. https://doi.org/10.1093/bja/85.2.217
Dobrogowski, J., Przeklasa-Muszyńska, A., Woroń, J., et al. (2007). Zasady kojarzenia leków w terapii bólu. Medycyna Paliatywna w Praktyce, 1(1), 6–15.
Bańka, K. (2022). Co wiemy o metamizolu? Przegląd literatury. Wydział Farmaceutyczny z Oddziałem Analityki Medycznej, Uniwersytet Medyczny im. Piastów Śląskich we Wrocławiu.
Tomidis Chatzimanouil, M. K., Goppelt, I., Zeissig, Y., Sachs, U. J., & Laass, M. W. (2023). Metamizole-induced agranulocytosis (MIA): A mini review. Molecular and Cellular Pediatrics, 10(1), 6. https://doi.org/10.1186/s40348-023-00160-8
Calvo, D. M., Saiz, L. C., Leache, L., Celaya, M. C., Gutiérrez-Valencia, M., Alonso, A., & Erviti, J. (2025). Does metamizole cause less acute kidney injury than non-steroidal anti-inflammatory drugs when combined with diuretics and antihypertensives? Toxics, 13(5), 417. https://doi.org/10.3390/toxics13050417
Kötter, T., da Costa, B. R., Fässler, M., Blozik, E., Linde, K., Jüni, P., Reichenbach, S., & Scherer, M. (2015). Metamizole-associated adverse events: A systematic review and meta-analysis. PLOS ONE, 10(4), e0122918. https://doi.org/10.1371/journal.pone.0122918
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Copyright (c) 2025 Julia Maszewska, Szymon Milnerowicz, Paulina Rzepa, Łukasz Brzost, Marta Danuta Cendrowska, Beata Choromańska, Julia Procyk, Justyna Berent, Karolina Stępień, Barbara Ponitka, Aleksandra Klukowska, Wiktoria Szumlińska
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