U M Stamer1, U Gundert-Remy2, E Biermann3, J Erlenwein4, W Meiβner5, S Wirz6, T Stammschulte2. 1. Klinik für Anästhesiologie und Schmerztherapie, Inselspital und Departement für Klinische Forschung, Universität Bern, Freiburgstr., 3010, Bern, Schweiz. ulrike.stamer@dkf.unibe.ch. 2. Arzneimittelkommission der Deutschen Ärzteschaft, Berlin, Deutschland. 3. Rechtsabteilung, Berufsverband Deutscher Anästhesisten, Nürnberg, Deutschland. 4. Klinik für Anästhesiologie, Universitätsmedizin Göttingen, Göttingen, Deutschland. 5. Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Jena, Jena, Deutschland. 6. Abteilung für Anästhesie, Intensivmedizin, Schmerzmedizin/Palliativmedizin, CURA - katholisches Krankenhaus im Siebengebirge, Bad Honnef, Deutschland.
Abstract
BACKGROUND: Dipyrone (metamizole) is a non-opioid analgesic commonly used in Germany, which can, in very rare cases, cause life-threatening agranulocytosis. The prescribing information calls for regular monitoring of the differential blood count in cases of long-term treatment. However, there is uncertainty about how this testing should be handled in practice. OBJECTIVES: Which recommendations can be derived from the published literature for evaluating blood cell counts during treatment with metamizole and which other options for monitoring exist? METHODS: Data from recent epidemiological studies, reviews, and spontaneously reported cases were evaluated. RESULTS: Agranulocytosis can emerge at highly variable intervals ranging from the first day of metamizole treatment to months after treatment has begun. As a result, there is no conclusive, evidence-based recommendation for the time intervals at which blood cell counts should be tested. Therefore, the onset of clinical symptoms should be used as trigger for monitoring blood cell counts to enable early diagnosis and avoid agranulocytosis-related complications. In addition to general symptoms like fever, sore throat, fatigue, and muscle pain, mucosal ulcerations, severe angina, and systemic infections leading to sepsis are typical of agranulocytosis. CONCLUSIONS: Providing patients and medical staff with better information about early symptoms of agranulocytosis could be a sensible way to prevent complications. Any suspicion of agranulocytosis should immediately lead to a differential blood count and to the withdrawal of all drugs possibly associated with agranulocytosis. Patients should be monitored and treated according to the severity of their symptoms.
BACKGROUND:Dipyrone (metamizole) is a non-opioid analgesic commonly used in Germany, which can, in very rare cases, cause life-threatening agranulocytosis. The prescribing information calls for regular monitoring of the differential blood count in cases of long-term treatment. However, there is uncertainty about how this testing should be handled in practice. OBJECTIVES: Which recommendations can be derived from the published literature for evaluating blood cell counts during treatment with metamizole and which other options for monitoring exist? METHODS: Data from recent epidemiological studies, reviews, and spontaneously reported cases were evaluated. RESULTS:Agranulocytosis can emerge at highly variable intervals ranging from the first day of metamizole treatment to months after treatment has begun. As a result, there is no conclusive, evidence-based recommendation for the time intervals at which blood cell counts should be tested. Therefore, the onset of clinical symptoms should be used as trigger for monitoring blood cell counts to enable early diagnosis and avoid agranulocytosis-related complications. In addition to general symptoms like fever, sore throat, fatigue, and muscle pain, mucosal ulcerations, severe angina, and systemic infections leading to sepsis are typical of agranulocytosis. CONCLUSIONS: Providing patients and medical staff with better information about early symptoms of agranulocytosis could be a sensible way to prevent complications. Any suspicion of agranulocytosis should immediately lead to a differential blood count and to the withdrawal of all drugs possibly associated with agranulocytosis. Patients should be monitored and treated according to the severity of their symptoms.
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