A systematic review and pharmacovigilance analysis of the risk of agranulocytosis associated with metamizole use.

Metamizole is an analgesic widely used after its introduction but later withdrawn in several countries due to the risk of agranulocytosis. Despite this, it remains frequently used worldwide. In June 2024, the Pharmacovigilance Risk Assessment Committee began reviewing metamizole-containing medicines. To assess the current evidence on this risk, we conducted a systematic review and a pharmacovigilance study using EudraVigilance to analyze data cases of agranulocytosis potentially associated with metamizole. In the systematic review, only 14 studies met our inclusion criteria, comprising case-control studies, registry-based descriptive analyses, and two pharmacovigilance studies. Current evidence on metamizole-induced agranulocytosis remains inconclusive. In our pharmacovigilance analysis (from 2003 to 2024), a total of 2244 reports were related to cases of agranulocytosis, of which 1397 (62.3%) related to female and adult patients 1148 (51.2%). The reporting odds ratio (ROR) with a 95% confidence interval (95% CI) showed a higher likelihood of reporting agranulocytosis with metamizole compared to clozapine (ROR: 5.50, 95% CI 5.18-5.82), sulfasalazine (ROR: 7.31, 95% CI 6.58-8.14), penicillamine (ROR: 34.4, 95% CI 11.70-167.89), and NSAIDs (ROR: 41.7, 95% CI 38.24-45.52). Our results confirm an increased likelihood of reporting agranulocytosis with metamizole. Given this risk and the availability of safer, effective alternatives, further research is needed.