Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children

Abstract

Objectives: Metamizole sodium (Novalgin ® ) is an effective, widely used analgesic and antipyretic agent in several countries. In spite of its availability and common usage, it has serious and potentially fatal adverse effects like agranulocytosis and aplastic anemia. Objectives of this study are to evaluate incidence, severity, and clinical significance of metamizole related neutropenia and agranulocytosis, and to study recovery duration of neutropenia and agranulocytosis in children exposed to metamizole. Material and Methods: Thirteen cases of neutropenia and/or agranulocytosis secondary to metamizole usage have been evaluated retrospectively. Duration and cumulative doses of metamizole, degree of neutropenia, recovery from neutropenia, and other complications related to neutropenia were evaluated. Results: Overall, thirteen granulocytopenic patients were recorded for 12 months after metamizol usage. Mean metamizole exposure duration was 4,64 (2-7) days; mean daily total metamizole dose was 40 (15,6-78) mg/kg; mean metamizole cumulative dose was 219,4 (58,8-468) mg/kg; mean neutropenia duration was 9,4 (1-30) days; and mean absolute neutrophil count was 690 (30-1300)/mm 3 . Four patients who used ≥ 30 mg/kg daily doses of metamizole for 4-7 days (≥ 217 mg/kg cumulative dose) had agranulocytosis. All of the patients recovered fully after metamizol cessasion. The shortest recorded recovery duration from granulocytopenia was 2 days while the longest recorded recovery duration was 30 days. Conclusion: Physicians should be aware of the toxic effects of metamizole and should not prefer metamizole as a first line antipyretic agent. Neutropenia and agranulocytosis risks should be kept in mind in the application of metamizole particularly over long periods of time and in large doses in children. Metamizol İlişkili Granulositopeni ve Agranülositoz: 13 Çocuğun DeğerlendirilmesiÖzet Amaç: Metamizol sodyum (Novalgin ® ) birçok ülkede yaygın olarak kullanılan etkili bir analjezik ve antipiretik ilaçtır. Yaygın kullanımına ve kolay elde edilebilirliğine rağmen agranülositoz ve aplastik anemi gibi ağır ve ölümcül olabilecek yan etkileri olabilir. Çalışmamızın amacı metamizol kullanan çocuklarda metamizol ilişkili nötropeni ve agranülositoz sıklığını, ağırlığını, klinik önemini ve nötropeni ve agranülositozdan çıkma sürelerini değerlendirmektir. Gereç ve Yöntemler: Metamizolle ilişkili 13 nötropeni ve agranülositoz vakası metamizol kullanım süresi, kümülatif dozu, nötropeniden çıkma süresi ve nötropeni ile ilişkili diğer komplikasyonlar açısından retrospektif olarak değerlendirildi. Bulgular: Metamizol kullanımı sonrası granülositopeni veya agranülositoz gelişen toplam 13 hasta tespit edildi. Ortanca metamizol kullanım süresi 4.64 (2-7) gün, ortanca günlük doz 40 (15.6-78) mg/kg, ortanca metamizol kümülatif dozu 219.4 (58.8-468) mg/kg, ortanca nötropeni süresi 9.4 (1-30) gün, ortanca mutlak nötrofil sayısı 690 (30-1300)/mm 3 olarak tespit edildi. 4-7 gün 30 mg/kg/gün'den (≥ 217 mg/kg kümülatif doz) fazla metamizol kullanan dör...

The effects of metamizole on hematopoietic progenitor cells: Suppression of hematopoiesis stimulation in vitro

“…During this period, granulocytopenia and agranulocytosis were detected in 13 children. The study results revealed that the incidence of metamizole-related agranulocytosis in pediatric patients admitted to the hospital was 1/10,000, and it was suggested that clinicians should not consider metamizole as the fi rst-line therapy in the paediatric population (11). Agranulocytosis was detected in one of the two cases with metamizole-related adverse effects in Antalya, Turkey.…”