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Metamizole-induced agranulocytosis (MIA): a mini review
Markos K Tomidis Chatzimanouil1, Ines Goppelt1, Yvonne Zeissig1
1Department of Pediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Abstract:
Metamizole is an analgesic, antipyretic, and spasmolytic drug in Germany only approved for the treatment of severe pain or high fever that does not respond to other measures. In recent years, an increased use has been described among both adults and children, often against the approved indication. The most important side effect of metamizole is the development of agranulocytosis (neutrophil count < 500/µL). Incidence of metamizole-induced agranulocytosis (MIA) ranges depending on the study from 0.96 cases per million per year to 1:1602 per patient and metamizole prescription. The risk of agranulocytosis in children remains unclear, but is probably lower than in adults. Female gender and older age are associated with higher incidence, reflecting prescription distribution. MIA is dose-independent and risk seems to increase with duration of intake. In patients with past exposure, re-exposure may lead to rapid onset. MIA is believed to be induced either through immunologic or toxic mechanisms. MIA presents with fever, sore throat, fatigue, and mucosal inflammation, up to ulceration. Even in the case of suspected MIA, treatment with metamizole should be immediately paused and an examination of the blood cell count is required. In case of local or systemic infections, empirical therapy with broad-spectrum antibiotics should be administered. G-CSF therapy should be limited to patients with poor prognostic factors. The patient should be monitored closely until the neutrophil count returns to normal. Re-exposure to metamizole must be avoided.
Insights
Metamizole, a pain and fever drug, can cause agranulocytosis, a dangerous drop in white blood cells. Immediate cessation of metamizole and blood count checks are crucial if agranulocytosis is suspected.
Area of Science:
- Pharmacology
- Hematology
- Drug Safety
Background:
- Metamizole is an analgesic, antipyretic, and spasmolytic drug approved in Germany for severe pain or fever unresponsive to other treatments.
- Increased off-label use of metamizole in adults and children has been observed.
- The primary safety concern with metamizole is the risk of developing agranulocytosis, a severe reduction in neutrophil count.
Purpose of the Study:
- To review the incidence, risk factors, mechanisms, clinical presentation, and management of metamizole-induced agranulocytosis (MIA).
Main Methods:
- Literature review and analysis of existing studies on metamizole usage and adverse events.
- Examination of incidence rates, demographic associations, and potential causative mechanisms of MIA.
- Outline of diagnostic and therapeutic strategies for suspected MIA cases.
Main Results:
- Incidence of MIA varies significantly across studies, ranging from 0.96 per million per year to 1:1602 per patient prescription.
- Risk factors include female gender and older age, likely reflecting prescription patterns. Risk may increase with duration of intake and is independent of dose.
- Re-exposure to metamizole in previously exposed patients can lead to rapid onset of MIA, which presents with symptoms like fever, sore throat, and mucosal inflammation.
Conclusions:
- Metamizole-induced agranulocytosis is a serious adverse event requiring immediate drug cessation and blood count monitoring.
- Prompt medical intervention, including antibiotics and potentially G-CSF for high-risk patients, is essential.
- Avoidance of re-exposure to metamizole is critical for patient safety.
