Metamizole and the risk of drug-induced agranulocytosis and neutropenia in statutory health insurance data

The non-opioid analgesic metamizole (dipyrone) is used for the treatment of acute and chronic pain and fever. Agranulocytosis is known as a serious adverse drug reaction of metamizole with potentially fatal outcome. However, its frequency is controversially discussed. The aim of our study was to determine the risk of metamizole-associated agranulocytosis and neutropenia using statutory health insurance data. We analyzed data from a large German health insurance fund in the period from 2010 to 2013. Metamizole-exposed subjects were identified and compared to a propensity score-matched control cohort. A total of 630,285 metamizole-treated subjects and 390,830 matched control subjects were included. In the metamizole cohort, ICD codes for agranulocytosis and neutropenia appeared more often than in non-users. The relative risk for drug-induced agranulocytosis and neutropenia (D70.1) was 3.03 (95% confidence interval, 2.49 to 3.69). The risk for developing drug-induced agranulocytosis and neutropenia after metamizole prescription was 1: 1602 (CI 95%, 1:1926 to 1:1371). Our results confirm the risk estimation of previous studies. However, the outcome of our study may be confounded by an association of metamizole treatment and chemotherapy. Therefore, consequences for treatment have to be drawn with care.