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Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children

Year 2015, Volume: 22 Issue: 2, 86 - 89, 09.12.2015

Abstract

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)/mm3. 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.

Key Words: Metamizole; Granulocytopenia; Agranulocytosis; Childhood.

References

  • Tekkok IH. Metamizole is not as safe as we think or assume. Turk Neurosurg 2011;21:116-7.
  • Bentur Y, Cohen O. Dipyrone overdose. J Toxicol Clin Toxicol 2004;42:261-5.
  • Isık M, Kaya Z, Belen FB, Aktas AT, Tezer H, Gursel T. Life-threatening agranulocytosis, anemia, and plasmacytosis after dipyroneuse for fever in a child. J Pediatr Hematol Oncol 2012;29:130-40.
  • Blake FG, Winternitz MC, Geiger AJ, Leonard JC, Opper L. Yale case studies: Agranulocytic anjina. Yale J Biol Med 1935;7:465-71.
  • Katz A. Aminopyrine, dipyrone and agranulocytosis. Canad Med Ass J 1964;91:1299-230.
  • Bäckström M, Hägg S, Mjörndal T, Dahlqvist R. Utilization pattern of metamizole in Northern Sweden and risk estimates of agranulocytosis. Pharmacoepidemiol Drug Safe 2002;11:239-45.
  • Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. The International Agranulocytosis and Aplastic Anemia Study. JAMA 1986;256:1749-57.
  • Basak GW, Drozd-Sokołowska J, Wiktor-Jedrzejczak W. Update on the incidence of metamizole sodium-induced blood dyscrasias in Poland. J Int Med Res 2010;38:1374-80.
  • Ibanez L, Vidal X, Ballarin E, Laporte JR. Agranulocutosis associated with dipyrone (metamizole). Eur J Clin Pharmacol 2005;60:821-9.
  • Hedenmalm K, Spigset O. Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole). Eur J Clin Pharmacol 2002;58:265-74.
  • van der Klauw MM, Goudsmit R, Halie MR, van't Veer MB, Herings RM, Wilson JH, et al. A population-based case-cohort study of drug-associated agranulocytosis. Arch Intern Med 1999;159:369–74.
  • Kiatboonsri P, Richter J. Dipyrone trials in Thailand. Lancet 1989;2:107.
  • 13. Vlahov V, Bacracheva N, Tontcheva D, Naumova E, Mavrudieva M, Ilieva P, et al. Genetic factors and risk of agranulocytosis from metamizol. Pharmacogenetics 1996;6:67-72.
  • Maj S, Lis Y. The incidence of metamizole sodium-induced agranulocytosis in Poland. J Int Med Res 2002;30:488-95.
  • Heit WF. Hematologic effects of antipyretic analgesics. Drug-induced agranulocytosis. Am J Med 1983;75:65-9.
  • Hargis JB, La Russa VF, Redmond J, Kessler SW, Wright DG. Agranulocytosis associated with Mexican aspirin (dipyron): evidence for an autoimmune mechanism affecting multipotential hematopoietic progenitors. Am J Hematol 1989;31:213-5.
  • Yetgin S, Ozyürek E, Aslan D, Cetin M. Metamizole sodium-induced severe aplastic anemia and its recovery with a short-course steroid therapy. Pediatr Hematol Oncol 2004;21:343-7.
  • Alves JG, Cardoso Neto FJ, Almeida CD, Almeida ND. Dipyrone and acetaminophen: correct dosing by parents? Sao Paulo Med J 2007;125:57-9.

Journal of Turgut Ozal Medical Center

Year 2015, Volume: 22 Issue: 2, 86 - 89, 09.12.2015

Abstract

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 gün, ortanca günlük doz 40 mg/kg, ortanca metamizol kümülatif dozu 219.4 mg/kg, ortanca nötropeni süresi 9.4 gün, ortanca mutlak nötrofil sayısı 690 /mm3 olarak tespit edildi. 4-7 gün 30 mg/kg/gün’den (≥ 217 mg/kg kümülatif doz) fazla metamizol kullanan dört hastada agranülositoz geliştiği ve bütün hastaların metamizol kesildikten sonra tam olarak düzeldikleri tespit edildi. En kısa granulositopeniden çıkma süresi 2 gün, en uzun süre ise 30 gündü. Sonuç: Klinisyenler metamizolün toksik etkilerinden haberdar olmalı ve metamizolü ilk sıra antipiretik ajan olarak tercih etmemelidirler. Özellikle uzun süreli ve yüksek dozlarda kullanımında nötropeni ve agranülositoz gelişebileceği akılda tutulmalıdır

References

  • Tekkok IH. Metamizole is not as safe as we think or assume. Turk Neurosurg 2011;21:116-7.
  • Bentur Y, Cohen O. Dipyrone overdose. J Toxicol Clin Toxicol 2004;42:261-5.
  • Isık M, Kaya Z, Belen FB, Aktas AT, Tezer H, Gursel T. Life-threatening agranulocytosis, anemia, and plasmacytosis after dipyroneuse for fever in a child. J Pediatr Hematol Oncol 2012;29:130-40.
  • Blake FG, Winternitz MC, Geiger AJ, Leonard JC, Opper L. Yale case studies: Agranulocytic anjina. Yale J Biol Med 1935;7:465-71.
  • Katz A. Aminopyrine, dipyrone and agranulocytosis. Canad Med Ass J 1964;91:1299-230.
  • Bäckström M, Hägg S, Mjörndal T, Dahlqvist R. Utilization pattern of metamizole in Northern Sweden and risk estimates of agranulocytosis. Pharmacoepidemiol Drug Safe 2002;11:239-45.
  • Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. The International Agranulocytosis and Aplastic Anemia Study. JAMA 1986;256:1749-57.
  • Basak GW, Drozd-Sokołowska J, Wiktor-Jedrzejczak W. Update on the incidence of metamizole sodium-induced blood dyscrasias in Poland. J Int Med Res 2010;38:1374-80.
  • Ibanez L, Vidal X, Ballarin E, Laporte JR. Agranulocutosis associated with dipyrone (metamizole). Eur J Clin Pharmacol 2005;60:821-9.
  • Hedenmalm K, Spigset O. Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole). Eur J Clin Pharmacol 2002;58:265-74.
  • van der Klauw MM, Goudsmit R, Halie MR, van't Veer MB, Herings RM, Wilson JH, et al. A population-based case-cohort study of drug-associated agranulocytosis. Arch Intern Med 1999;159:369–74.
  • Kiatboonsri P, Richter J. Dipyrone trials in Thailand. Lancet 1989;2:107.
  • 13. Vlahov V, Bacracheva N, Tontcheva D, Naumova E, Mavrudieva M, Ilieva P, et al. Genetic factors and risk of agranulocytosis from metamizol. Pharmacogenetics 1996;6:67-72.
  • Maj S, Lis Y. The incidence of metamizole sodium-induced agranulocytosis in Poland. J Int Med Res 2002;30:488-95.
  • Heit WF. Hematologic effects of antipyretic analgesics. Drug-induced agranulocytosis. Am J Med 1983;75:65-9.
  • Hargis JB, La Russa VF, Redmond J, Kessler SW, Wright DG. Agranulocytosis associated with Mexican aspirin (dipyron): evidence for an autoimmune mechanism affecting multipotential hematopoietic progenitors. Am J Hematol 1989;31:213-5.
  • Yetgin S, Ozyürek E, Aslan D, Cetin M. Metamizole sodium-induced severe aplastic anemia and its recovery with a short-course steroid therapy. Pediatr Hematol Oncol 2004;21:343-7.
  • Alves JG, Cardoso Neto FJ, Almeida CD, Almeida ND. Dipyrone and acetaminophen: correct dosing by parents? Sao Paulo Med J 2007;125:57-9.
There are 18 citations in total.

Details

Primary Language ingilizce
Journal Section Articles
Authors

Arzu Akyay This is me

Uğur Deveci This is me

Publication Date December 9, 2015
Published in Issue Year 2015 Volume: 22 Issue: 2

Cite

APA Akyay, A., & Deveci, U. (2015). Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children. Journal of Turgut Ozal Medical Center, 22(2), 86-89.
AMA Akyay A, Deveci U. Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children. J Turgut Ozal Med Cent. December 2015;22(2):86-89.
Chicago Akyay, Arzu, and Uğur Deveci. “Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children”. Journal of Turgut Ozal Medical Center 22, no. 2 (December 2015): 86-89.
EndNote Akyay A, Deveci U (December 1, 2015) Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children. Journal of Turgut Ozal Medical Center 22 2 86–89.
IEEE A. Akyay and U. Deveci, “Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children”, J Turgut Ozal Med Cent, vol. 22, no. 2, pp. 86–89, 2015.
ISNAD Akyay, Arzu - Deveci, Uğur. “Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children”. Journal of Turgut Ozal Medical Center 22/2 (December 2015), 86-89.
JAMA Akyay A, Deveci U. Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children. J Turgut Ozal Med Cent. 2015;22:86–89.
MLA Akyay, Arzu and Uğur Deveci. “Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children”. Journal of Turgut Ozal Medical Center, vol. 22, no. 2, 2015, pp. 86-89.
Vancouver Akyay A, Deveci U. Metamizole Related Granulocytopenia and Agranulocytosis: An Analysis of 13 Children. J Turgut Ozal Med Cent. 2015;22(2):86-9.