Is There an Increased Risk of Hepatotoxicity with Metamizole? A Comparative Cohort Study in Incident Users

Hedenmalm, Karin; Păcurariu, Alexandra; Slattery, Jim; Kurz, Xavier; Candore, Gianmario; Flynn, Rob

doi:10.1007/s40264-021-01087-7

Cited by 7 publications

(4 citation statements)

References 56 publications

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“…As the studies cover several aspects related to the safety implications of dipyrone therapy, a didactic division has been made to group the issues in the discussion: dipyrone in children [22][23][24][25][26][27], dipyrone during pregnancy [28], dipyrone and blood dyscrasias [29][30][31][32][33][34], dipyrone in specific diseases [35][36][37][38][39][40][41][42][43][44], in addition to anaphylactic reactions and general adverse effects of dipyrone [45][46][47][48][49][50][51]. About the quality of the studies, it is worth mentioning the scarcity of clinical trials, with the majority being of observational retrospective or cohort design (n = 27).…”

Section: Resultsmentioning

confidence: 99%

“…There were no cases of injury in children. Of the patients using dipyrone, some of them developed significant liver events (liver failure, liver disease, among others), while those using paracetamol had comparatively fewer events [40]. This shows that there is a great concern about the hepatotoxicity of paracetamol, also because the mechanisms are already well established, while the risks with dipyrone are neglected.…”

Section: Dipyrone In Specific Diseasesmentioning

confidence: 99%

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One hundred years of dipyrone (metamizole): the recent evidence on its safety

Malheiro

Viana²,

Nascimento³

et al. 2023

PRW

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Dipyrone is a non-opioid analgesic drug used for fever and many types of pain. Due to the risk of induced agranulocytosis, it was banned in the early 1980s in several countries, but is still widely used in Brazil, Mexico, China and others. This study is a systematic review of literature focusing on the recent evidence about dipyrone safety. To this, a literature search was performed for epidemiological studies published between 2015 and 2022, in English, German, Portuguese, and Spanish languages. From the 30 articles that met the inclusion criteria, most of them consisted in observational studies (n = 27). In children, the frequency of adverse events with dipyrone is low, but can affect the renal and circulatory systems. During pregnancy, the drug doesn't seem to be related to teratogenic abnormalities. Agranulocytosis is still a matter of debate. However, the occurrence is rare, with an estimated risk of 1:1,602. In adults, dipyrone is related to several adverse effects on renal, hepatic, respiratory and epidermal systems. Thus, dipyrone seems to have a low incidence of adverse effects, but some can be considered of high severity. Especially in children, elderly and patients who need treatment for long periods, other analgesic options should be evaluated.

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Section: Resultsmentioning

confidence: 99%

Section: Dipyrone In Specific Diseasesmentioning

confidence: 99%

One hundred years of dipyrone (metamizole): the recent evidence on its safety

Malheiro

Viana²,

Nascimento³

et al. 2023

PRW

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“…В двух немецких когортных исследованиях, результаты которых были опубликованы в 2020-2021 гг., доля лекарственно-индуцированных поражений печени (ЛПП) при применении МН составляла 13-15% среди всех случаев ЛПП, что авторы объяснили ростом потребления данного препарата [58,59]. Высокий риск гепатотоксичности МН был отмечен в результате анализа информации за 2009-2018 гг., содержащейся в базе данных Intercontinental Medical Statistics (IMS)® Disease Analyzer (сведения по Германии), проведенном с целью сравнения риска развития ЛПП в течение 270 сут после начала лечения МН или парацетамолом [60]. По результатам исследования применение МН было ассоциировано с более высоким риском ЛПП по сравнению с парацетамолом (скорректированное отношение рисков 1,69, 95% ДИ 1,46-1,97).…”

Section: нежелательные реакцииunclassified

Sodium Metamizole: Regulatory Status around the World, Safety Problems and Medication Errors

Ушкалова

Zyryanov

Бутранова

et al. 2022

Bezopasnost' i risk farmakoterapii

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Sodium metamizole (SM), analgin, was recalled from the pharmaceutical market by the regulatory authorities of some countries in the mid-60s because of side effects (agranulocytosis). However, there has been a trend towards a steady increase in its prescription rates in the recent decades. The aim of the study was to characterise the regulatory status of SM in different countries of the world, to assess the effectiveness and safety, and to analyse available data on medication errors in real clinical practice. According to the reviewed publications, SM is the most frequently used analgesic in surgical practice in German-speaking countries, the third most frequently prescribed analgesic in Switzerland, and a widely used one even in the countries where it has previously been recalled, such as the USA. The increase in the use of SM, according to experts, is due to the opioid crisis and the high risk of cardiotoxicity of non-steroidal anti-inflammatory drugs (NSAIDs). In chronic pain, the efficacy of SM is superior to that not only of paracetamol, but also of NSAIDs; in postoperative pain and acute primary headache, it is not lower than that of other commonly used analgesics. SM has a pronounced analgesic effect in cancer patients; high doses are comparable to narcotic analgesics in effectiveness but have a significantly more favourable safety profile. Randomised and observational studies confirm that the short-term use of SM is quite safe, including in terms of the risk of developing myelosuppressive side effects. When administered as a course of less than 2 weeks, SM is characterised by a lower frequency of adverse events compared to opioids and an approximately equal one compared to placebo and paracetamol, while longer courses are associated with an increased risk of agranulocytosis. Adverse drug reactions may result from medication errors. The risk of lethal outcome associated with agranulocytosis increases when SM is co-administered with methotrexate or used in elderly patients. In the Russian Federation, SM is an over-the-counter medicinal product approved for a wide range of pain types; it can be used as a highly effective analgesic provided that the dose, route, and frequency of administration are appropriate, the baseline characteristics of patients are taken into account, and unreasonably long courses (more than 2 weeks) are avoided.

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“…Although it is emphasized to be safer when compared to other analgesics especially for the treatment of short-term pain, information about its safety in medium and long-term use is limited 3 . Previous studies have revealed that metamizole is associated with a major risk of liver injury 7 . In addition, it has been proven in previous studies that diclofenac, another NSAID drug other than metamizole, has a toxic effect on the liver 8 .…”

Section: Introductionmentioning

confidence: 99%

Effect of Thiamine Pyrophosphate upon Possible Metamizole-Induced Liver Injury in Rats

Bedir¹,

Ozkaloglu²,

Can³

et al. 2023

International J. of Pharmacology

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Background and Objective: Metamizole is a non-selective cyclooxygenase (COX) inhibitor NSAID with a strong analgesic and spasmolytic effects. It is the most common analgesic in the world. Thiamine pyrophosphate (TPP) protects the liver tissue against oxidative damage. The aim of our study was to analyze the effect of TPP against possible liver injury and dysfunction of metamizole in rats biochemically and histopathologically. Materials and Methods: The animals were grouped as healthy (HG), 500 mg kgG 1 metamizole (MT-500), 1000 mg kgG 1 metamizole (MT-1000), 25 mg kgG 1 TPP+500 mg kgG 1 metamizole (TMT-500), 25 mg kgG 1 TPP+1000 mg kgG 1 metamizole (TMT-1000) groups. The TMT-500 and TMT-1000 groups of animals were injected intraperitoneally (ip) at the dose of 25 mg kgG 1 of TPP. Distilled water as the solvent was injected ip to the HG, MT-500 and MT-100 groups. One hour after injecting TPP and distilled water, metamizole 500 and 1000 mg kgG 1 doses were administered orally to the TMT-500 and TMT-1000 groups. The TPP was administered once and metamizole twice a day for 14 days. The animals were euthanized with high-dose anesthesia. The liver tissues excised from the animals were analyzed biochemically and histopathologically. Results: In both doses metamizole significantly increased MDA, ALT and AST levels and decreased tGSH, SOD and CAT levels compared to the healthy group. TPP significantly prevented the decrease of tGSH, SOD and CAT levels and the increase of MDA, ALT and AST levels with metamizole. There was no statistical difference in all of the levels between the TMT-500 and TMT-1000 groups. The histopathological findings indicated TPP significantly suppressed the damage induced by metamizole. Conclusion: The metamizole was possible to cause moderate damage to liver tissue. Therefore, it was considered that the use of TTP to reduce liver toxicity could be clinically beneficial.

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Is There an Increased Risk of Hepatotoxicity with Metamizole? A Comparative Cohort Study in Incident Users

Cited by 7 publications

References 56 publications

One hundred years of dipyrone (metamizole): the recent evidence on its safety

One hundred years of dipyrone (metamizole): the recent evidence on its safety

Sodium Metamizole: Regulatory Status around the World, Safety Problems and Medication Errors

Effect of Thiamine Pyrophosphate upon Possible Metamizole-Induced Liver Injury in Rats

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