Keywords
dipyrone
methimazole
adverse reaction.
Abstract
Introduction: Acute pain is highly prevalent in The Hospital Settings and in the emergency department. Dipyrone (metamizole) is a widely used medication for acute pain syndromes, such as postoperative pain. This study aims to characterize the adverse drug reactions (ADRs) most frequently associated with dipyrone. Materials and methods: This is a study based on records in the Colombian database of the National Institute for Food and Drug Surveillance (INVIMA). Incidences were calculated and characteristics related to non-recoverable ADRs were determined. Results: A total of 1833 prescriptions of dipyrone were recorded, corresponding to 4021 medication-related problems (3868 ADRs, 96.19 %). The incidence of MRP due to dipyrone was 101 per 100,000 unique prescribed patients. Women accounted for 54.55% of the patients, and the median age was 28 years (IQR 10-46). The most frequent ADRs were skin rash (905; 24.78 %), pruritus (561; 15.36 %), and urticaria (365; 9.99 %). Thirtyeight ADRs affected the hematologic system (0.98 %). Hematologic ADRs in women had a higher probability of non-recovery (OR 14.52 IQR 5.25-40.20; p = 0.000). Conclusions: In Colombia, the most common ADRs associated with dipyrone affect the skin and its appendages. Unlike the incidence in patients of other ethnicities, hematologic ADRs are rare but are associated with a lower probability of recovery.References
1. Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 2020;161(9):1976-82.
2. Hachimi-Idrissi S, Coffey F, Hautz WE, Leach R, Sauter TC, Sforzi I, et al. Approaching acute pain in emergency settings: European Society for Emergency Medicine (EUSEM) guidelines-part 1: Assessment. Intern Emerg Med. 2020;15(7):1125-39.
3. Erazo MA, Pérez L, Colmenares CC, Álvarez H, Suárez I, Mendivelso F. Prevalencia y caracterización del dolor en pacientes hospitalizados. Revista de la Sociedad Española del Dolor. 2015;22(6):241-8.
4. Hoffmann F, Meinecke P, Freitag MH, Glaeske G, Schulze J, Schmiemann G. Who gets dipyrone (metamizole) in Germany? Prescribing by age, sex and region. J Clin Pharm Ther. 2015;40(3):285-8.
5. Ramacciotti AS, Soares BGO, Atallah AN. Dipyrone for acute primary headaches. Cochrane Database Syst Rev. 2007;2:CD004842.
6. Derry S, Faura C, Edwards J, McQuay HJ, Andrew Moore R. Single dose dipyrone for acute postoperative pain. Cochrane Database of Systematic Reviews. 2010;9:CD003227.
7. Gaertner J, Stamer UM, Remi C, Voltz R, Bausewein C, Sabatowski R, et al. Metamizole/dipyrone for the relief of cancer pain: A systematic review and evidence-based recommendations for clinical practice. Palliat Med. 2017;31(1):26-34.
8. Nikolova I, Petkova V, Tencheva J, Benbasat N, Voinikov J, Danchev N. Metamizole: A review profile of a well-known “forgotten” drug. Part II: Clinical profile. Biotechnology & Biotechnological Equipment. 2013;27(2):3605-19.
9. ATC/DDD Index [Internet]. WHO; 2023 [consultado el 5 de julio de 2022]. Disponible en: https://www.whocc.no/atc_ddd_index/
10. Estadísticas de Medicamentos, MEDCOL-STAT [Internet]. Ministerio de Salud de Colombia; 2022 [consultado el 5 de abril de 2022]. Disponible en: https://pospopuli.minsalud.gov.co/MEDCOL-STAT /POSEstadisticasMedicamentos.aspx
11. Pinilla-Monsalve GD, Reyes-Rueda M, Pinilla-Monsalve LA. Problemas y reacciones adversas relacionadas con analgésicos opioides en Colombia. Rev Neurol. 2021;73:39.
12. Frome EL, Checkoway H. Use of Poisson regression models in estimating in estimating incidence rates and ratios. American Journal of Epidemiology. 1985;121(2):309-23.
13. González-Cárdenas VH, Laverde-Gaona LA, Cabarique-Serrano SH, Chávez-Rojas N, Reina-Sierra JA, Infante JS, et al. Analysis of the incidence of adverse events related to the administration of dipyrone. Colombian Journal of Anesthesiology. 2018;46(2):119-25.
14. Machado-Alba JE, Cardona-Trejos EA, Sánchez-Morales LV, Rodríguez-Ramírez LF. Identificación de reacciones adversas medicamentosas en pacientes tratados con dipirona en un hospital de tercer nivel. CES Medicina. 2019;33(1):13-20.
15. Hernández-Salazar A, Rosales SP de L, Rangel-Frausto S, Criollo E, Archer-Dubon C, Orozco-Topete R. Epidemiology of adverse cutaneous drug reactions. A prospective study in hospitalized patients. Arch Med Res. 2006;37(7):899-902.
16. Trautmann A, Brockow K, Stoevesandt J. Metamizole-induced reactions as a paradigm of drug hypersensitivity: Non-allergic reactions, anaphylaxis, and delayed-type allergy. Clin Exp Allergy. 2020;50(9):1103-6.
17. Blanca-López N, Pérez-Sánchez N, Agúndez JA, García-Martin E, Torres MJ, Cornejo-García JA, et al. Allergic reactions to metamizole: Immediate and delayed responses. Int Arch Allergy Immunol. 2016;169(4):223-30.
18. Hoffmann F, Bantel C, Jobski K. Agranulocytosis attributed to metamizole: An analysis of spontaneous reports in EudraVigilance 1985‐2017. Basic & Clinical Pharmacology & Toxicology. 2020;126(2):116-25.
19. Blaser LS, Tramonti A, Egger P, Haschke M, Krähenbühl S, Rätz Bravo AE. Hematological safety of metamizole: Retrospective analysis of WHO and Swiss spontaneous safety reports. Eur J Clin Pharmacol. 2015;71(2):209-17.
20. Stammschulte T, Ludwig WD, Mühlbauer B, Bronder E, Gundert-Remy U. Metamizole (dipyrone)-associated agranulocytosis. An analysis of German spontaneous reports 1990–2012. European Journal of Clinical Pharmacology. 2015;71(9):1129-38.
21. Hedenmalm K, Spigset O. Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole). Eur J Clin Pharmacol. 2002;58(4):265-74.
22. Shah RR. Metamizole (dipyrone)-induced agranulocytosis: Does the risk vary according to ethnicity? J Clin Pharm Ther. 2019;44(1):129-33.
23. 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(1):67-72.
24. Lutz M. Metamizole (dipyrone) and the liver: A review of the literature. J Clin Pharmacol. 2019; 59(11):1433-42.
25. Collares EF, Troncon LEA. Effects of dipyrone on the digestive tract. Braz J Med Biol Res. 2019;52(2):e8103.
26. Weber S, Benesic A, Neumann J, Gerbes AL. Liver injury associated with metamizole exposure: Features of an underestimated adverse event. Drug Saf. 2021;44(6):669-80.