Comparative safety profile of Metamizole, Viminol, and Tapentadol: a prospective observational study on adverse reactions
DOI:
https://doi.org/10.1590/s2175-97902026e24933Keywords:
Analgesics, Pharmacovigilance, Drug-Related Side Effects and Adverse Reactions, Drug Monitoring, Adverse Drug Reactions (ADRs), Safety Monitoring or Risk ManagementAbstract
The most potent analgesics cause serious Adverse Drug Reactions (ADRs), so medications such as metamizole, viminol, and tapentadol may be alternatives. However, the safety of these analgesics still needs to be better understood. This study aims to assess prospective ADRs associated with these analgesics in a pain clinic. We followed up with the patients who had used these medicines for 45 days, classified the ADRs according to severity (mild, moderate or severe), mechanism (type A or type B), and incidence (very common, common, uncommon, and rare), and determined the causality. Among 240 patients, three ADRs to metamizole, seven to viminol, and 11 to tapentadol alone were documented. Additionally, 22 suspected ADRs were attributed to potential drug interactions among these analgesics and other medications. The ADRs were categorized as mild to moderate, type A, and common or uncommon. Causality was categorized as certain or possible. The ADRs induced by viminol were associated with age, with each year of age leading to a 6% increase in risk of ADRs, according to a logistic regression model applied specifically to this drug. No other association was found between tapentadol or viminol and comorbidities. It was not possible to analyze the metamizole data due to its low incidence. Overall, metamizole was the safest, reinforcing its safety profile and its valuable indication in the treatment of pain.
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Abeyaratne C, Lalic S, Bell JS, Ilomäki J. Spontaneously reported adverse drug events related to tapentadol and oxycodone/naloxone in Australia. Ther Adv Drug Saf. 2018;9(4):197-205.
Al-Qurain AA, Gebremichael LG, Khan MS, Williams DB, Mackenzie L, Phillips C, et al. Prevalence and factors associated with analgesic prescribing in poly-medicated elderly patients. Drugs Aging. 2020;37(4):291-300.
ANVISA (National Health Surveillance Agency). Register Dividol na ANVISA [Internet], Brasília, DF, 2024 [Cited April 10, 2024]. Available from: https://anvisa.smerp.com.br/?ac=prodDetail&anvisaId=1008400200024.
Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol. 2020;180:114147.
Cazacu I, Stroe R, Dondera R, Mogosan C, Haramburu F, Fourrier-Réglat A, Loghin F. Adverse drug reactions of analgesic medicines: analysis of the Romanian pharmacovigilance database. Fundam Clin Pharmacol. 2018;32(3):330-336.
Coluzzi F, Ruggeri M. Valutazione clinica ed economica di nuovi analgesici per la gestione del dolore cronico. Recenti Prog Med. 2014;105(11):415-419.
Crestan D, Trojniak MP, Francescon S, Fornasier G, Baldo P. Pharmacovigilance of anti-cancer medicines: opportunities and challenges. Expert Opin Drug Saf. 2020;19(7):849-860.
Dalal S, Bruera E. Pain management for patients with advanced cancer in the opioid epidemic era. Am Soc Clin Oncol Educ Book. 2019;39:24-35.
David-Pereira A, Dickenson AH. Issues in the future development of new analgesic drugs. Curr Opin Support Palliat Care. 2019;13(2):107-110.
Dividol [MONOGRAPHY]. São Paulo: Zambon Laboratory. Ed. Phoenix Integrated Communication. February 2020.
DRUGS.COM. [Cited 2024 Aug 21]. Available from: https://www.drugs.com.
Foschi D, Ventresca GP, Lodola E. Analgesic activity of viminol R2 in postoperative pain: comparison with pentazocine and placebo. Curr Ther Res - Clin Exp. 1985;37:269-276.
Franconi F, Campesi I, Occhioni S, Antonini P, Murphy MF. Sex and gender in adverse drug events, addiction, and placebo. Handb Exp Pharmacol. 2012;214:107-126.
Freynhagen R, Elling C, Radic T, Sohns M, Liedgens H, James D, et al. Safety of tapentadol compared with other opioids in chronic pain treatment: network meta-analysis of randomized controlled and withdrawal trials. Curr Med Res Opin. 2021;37(1):89-100.
Frigerio G. Il viminolo nel trattamento del dolore. Ricerca controllata doppio-cieca di tipo multicentrico. Minerva Med. 1974;65(12):687-703.
Hartwig SC, Siegel J, Schneider PJ. Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm. 1992;49:2229-2232.
Jo HG, Jeong K, Ryu JY, Park S, Choi YS, Kwack WG, et al. Fatal Events Associated with adverse drug reactions in the Korean national pharmacovigilance database. J Pers Med. 2021;12(1):5.
Klose S, Pflock R, König IR, Linder R, Schwaninger M. Metamizole and the risk of drug-induced agranulocytosis and neutropenia in statutory health insurance data. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(4):681-690.
Kötter T, da Costa BR, Fässler M, Blozik E, Linde K, Jüni P, et al. Metamizole-associated adverse events: a systematic review and meta-analysis. PLoS One. 2015;13;10(4):e0122918.
Lobo MGAA, Pinheiro SMB, Castro JGD, Momenté VG, Pranchevicius MCS. Adverse drug reaction monitoring: support for pharmacovigilance at a tertiary care hospital in Northern Brazil. BMC Pharmacol Toxicol. 2013;14:5.
Lopes GS, Bielinski S, Moyer AM, Jacobson DJ, Wang L, Jiang R, Larson NB, Miller VM, Zhu Y, Cavanaugh DC, St Sauver J. Sex differences in type and occurrence of adverse reactions to opioid analgesics: a retrospective cohort study. BMJ Open. 2021;11(6):e044157.
LupuG, Bel L, Andrei S. Pain management and analgesics used in small mammals during post-operative period with an emphasis on metamizole (dipyrone) as an alternative medication. Molecules. 2022;27:7434.
Martinetti L, Lodola E, Monafo V, Ferrari V. Clinical evaluation of an oral analgesic, Z.424, in patients with chronic pain.J Clin Pharmacol New Drug. 1970;10(6):390-399.
Mateos RG, Bernal DS, Morera LMT, Ferri CM, Escobar AE. Long-term effectiveness and tolerability of pain treatment with tapentadol prolonged release. Pain physician. 2021;24(1):E75–E85.
Meyboom RHB, Egberts ACG. Comparing therapeutic benefit and risk. Thérapie. 1999;54(1):29-34.
Mijovic A, MacCabe JH. Clozapine-induced agranulocytosis. Ann Hematol. 2020;99(11):2477-2482.
Montané E, Santesmases J. Adverse drug reactions. Med Clin (Barc). 2020;13;154(5):178-184.
Ognibene S, Vazzana N, Giumelli C, Savoldi L, Braglia L, Chesi G. Hospitalisation and morbidity due to adverse drug reactions in elderly patients: a single-centre study. Intern Med J. 2018;48(10):1192-1197.
Onakpoya IJ, Heneghan CJ, Aronson JK. Post-marketing withdrawal of analgesic medications because of adverse drug reactions: a systematic review. Expert Opin Drug Saf. 2018;17(1):63-72.
Planelles B, Margarit C, Ajo R, Sastre Y, Muriel J, Inda MD, Esteban MD, Peiró AM. Health benefits of an adverse events reporting system for chronic pain patients using long-term opioids. Acta Anaesthesiol Scand. 2019;63(2):248-258.
Rawlins MD, Thompson JW. Pathogenesis of adverse drug reactions. In:Davies DM, editor. Textbook of adverse drug reactions. Oxford: Oxford University Press;1977.
Reist L, Erlenwein J, Meissner W, Stammschulte T, Stüber F, Stamer UM. Metamizole is the preferred nonopioid analgesic for the treatment of acute and chronic pain. A survey of clinical practice in German-speaking countries. Eur J Pain. 2018;22(6):1103-1112.
Riera P, Sole N, Suárez JC, López PA, Fonts N, Rodríguez-Farre N, et al. Drug-drug interactions in an intensive care unit and comparison of updates in two databases. Farm Hosp. 2022;46(5):290-295.
Sakuma M, Kanemoto Y, Furuse A, Bates DW, Morimoto T. Frequency and severity of adverse drug events by medication classes: the JADE study. J Patient Saf. 2020;16(1):30-35.
Shook JE, Kallman MJ, Dewey WL. The discriminative stimulus properties of the R2 isomer of viminol. Pharmacol Biochem Behav. 1984;20(1):59-62.
Sznejder H, Amand C, Stewart A, Salazar R, Scala WA. Real world evidence of the use of metamizole (dipyrone) by the Brazilian population. A retrospective cohort with over 380,000 patients. Einstein(Sao Paulo). 2022;20:eAO6353.
Tzschentke TM, Christoph T, Kögel B, Schiene K, Hennies HH, Englberger W, et al. (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): a novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J Pharmacol Exp Ther. 2007;323(1):265-76.
Tzschentke TM, Christoph T, Kögel BY. The mu-opioid receptor agonist/noradrenaline reuptake inhibition (MOR-NRI) concept in analgesia: the case of tapentadol. CNS Drugs. 2014;28(4):319-29.
UpToDate®. Connor RF (Ed). [Cited 2024 Jun 15]. Available from: http://www.uptodate.com.
Volkow ND, Blanco C. The changing opioid crisis: development, challenges and opportunities. Mol Psychiatry. 2021;26(1):218-233.
Woo SD, Yoon J, Doo GE, Park Y, Lee Y, Lee SH, et al.. Common causes and characteristics of adverse drug reactions in older adults: a retrospective study. BMC Pharmacol Toxicol. 2020;21(1):87.
World Health Organization. The use of the WHO-UMC system for standardized case causality assessment. Uppsala Monit Cent. 2005;3:2–7.
Zazzara MB, Palmer K, Vetrano DL, Carfì A, Onder G. Adverse drug reactions in older adults: a narrative review of the literature. Eur Geriatr Med. 2021;12(3):463-473.
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