Metamizole: An underrated agent causing severe idiosyncratic drug‐induced liver injury

Abstract

Drug-induced liver injury (DILI) is a heterogenous entity leading to liver damage. We have analysed the frequency, biochemical and histological patterns and clinical courses of DILI cases due to metamizole at our tertiary care centre in Hamburg, Germany.Methods: Consecutive patients with DILI who presented to our clinic were analysed retrospectively. Causes of acute hepatitis other than DILI were excluded.

Further evidence for the hepatotoxic potential of metamizole

“…Causality assessment was supported by the MH cell test, for which a sensitivity and specificity of 92% and 100%, respectively, have been shown previously in a selected cohort of DILI patients with positive rechallenge. 10 In accordance with Sebode et al, 5 we observed a hepatocellular phenotype in most cases. The median latency between initiation of metamizole therapy and onset of liver injury was 52 days, and median average daily dose was 1000 mg.…”

“…In conclusion, as part of our prospective study on the hepatotoxic potential of drugs, we identified 10 patients with metamizole-induced DILI, who presented with a similar pattern as the previously described cases. 1,5 Metamizole was the most likely causative agent with RUCAM scores of 6 to 9 and a positive rechallenge in 40% of the cases. We therefore support Björnsson's statement that the hepatoxic potential of metamizole has been clearly demonstrated by now.…”

“…However, despite its extensive hepatic metabolism, the potential of metamizole to cause drug‐induced liver injury (DILI) has been disregarded for many years, and only few cases have been reported 4 . Björnsson emphasizes 1 that including recently published cases by Sebode et al, 5 approximately 40 patients with metamizole‐induced liver injury have been reported worldwide, which qualifies metamizole as a Category B drug causing DILI according to the categorization system of LiverTox (http://livertox.nih.gov). 6 As stated by the LiverTox “likelihood score,” Category A drugs are considered to have a definite hepatotoxic potential with a positive rechallenge reported for almost 90% of the drugs, while Category B drugs are highly likely to cause DILI 6,7 .…”

Liver Injury Associated with Metamizole Exposure: Features of an Underestimated Adverse Event

“…Considering the extensive hepatic metabolism of metamizole, mainly mediated by cytochrome P450 [5], its lipophilicity and the relatively high daily dose, all of which are known risk factors for druginduced liver injury (DILI) [6,7], it is surprising that the hepatotoxic potential has not been a topic for pharmacovigilance until now. Interestingly, Sebode et al reported 23 cases of metamizole-induced DILI recently, which corresponded to 15% of all the DILI cases included in their centre [8]. The majority of the cases presented with a hepatocellular type of injury, nearly 50% of patients fulfilled Hy's law criteria, meaning alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) and total bilirubin (TBIL) > 2 × ULN, and 9% of the patients developed ALF [8].…”

“…Interestingly, Sebode et al reported 23 cases of metamizole-induced DILI recently, which corresponded to 15% of all the DILI cases included in their centre [8]. The majority of the cases presented with a hepatocellular type of injury, nearly 50% of patients fulfilled Hy's law criteria, meaning alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) and total bilirubin (TBIL) > 2 × ULN, and 9% of the patients developed ALF [8].…”