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Metamizole (dipyrone)-associated agranulocytosis. An analysis of German spontaneous reports 1990-2012

Thomas Stammschulte1, Wolf-Dieter Ludwig, Bernd Mühlbauer

  • 1Drug Commission of the German Medical Association (DCGMA), Herbert-Lewin-Platz 1, 10623, Berlin, Germany, thomas.stammschulte@akdae.de.

European Journal of Clinical Pharmacology
|July 15, 2015
PubMed
Abstract

Insights

Metamizole prescriptions and agranulocytosis reports increased significantly in Germany. This analysis of metamizole-induced agranulocytosis cases highlights severe outcomes and the need for better risk management strategies.

Area of Science:

  • Pharmacovigilance
  • Clinical Pharmacology
  • Drug Safety

Background:

  • Metamizole use restrictions were implemented in Germany in 1986 due to agranulocytosis risk.
  • Despite restrictions, metamizole prescriptions surged from under 20 million DDD in 1990 to over 140 million DDD in 2012.
  • Concurrently, spontaneous reports of agranulocytosis rose from approximately 10 to over 50 during the same period.

Purpose of the Study:

  • To analyze reports of metamizole-induced agranulocytosis to identify targets for risk minimization measures.
  • To assess patient characteristics, indications, clinical course, and outcomes of metamizole-associated agranulocytosis.
  • To evaluate the impact of increased metamizole use on agranulocytosis incidence and severity.

Main Methods:

  • Analysis of suspected metamizole-induced agranulocytosis cases reported in the German spontaneous reporting database from 1990 to 2012.
  • Inclusion criteria: neutrophils < 0.5 × 10(9) cells/l and availability of original reporting documents.
  • Assessment of patient demographics, drug indications, treatment duration, clinical presentation, and patient outcomes.

Main Results:

  • 161 reports of metamizole-induced agranulocytosis were analyzed; mean patient age was 56.8 years, with 64.6% females.
  • Off-label use was noted in approximately 25% of cases. Severe neutropenia (<100/μl) occurred in 63 patients, and 109 experienced intercurrent infections.
  • Mortality was 23.6% (38 patients). Agranulocytosis onset varied, with two-thirds occurring within 6 weeks of treatment, and 18 cases showing immediate onset after initial doses.

Conclusions:

  • Metamizole-associated agranulocytosis cases frequently present with severe clinical courses, partly due to off-label use.
  • The lack of identifiable individual risk factors and variable onset patterns necessitate focused risk minimization.
  • Recommendations include restricting metamizole use to specific clinical situations and enhancing risk communication for patients and healthcare providers.

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