Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Original article

Vol. 154 No. 2 (2024)

Use of metamizole and other non-opioid analgesics in Switzerland between 2014 and 2019: an observational study using a large health insurance claims database

  • Stephan Gut
  • Marlene Rauch
  • Manuel Haschke
  • Carola A. Huber
  • Jan Gaertner
  • Nadine Schur
  • Christoph R. Meier
  • Julia Spoendlin
DOI
https://doi.org/10.57187/s.3535
Cite this as:
Swiss Med Wkly. 2024;154:3535
Published
05.02.2024

Summary

OBJECTIVE: To investigate claims patterns for metamizole and other non-opioid analgesics in Switzerland. To characterise users of these non-opioid analgesics regarding sex, age, comedications and canton of residence.

METHODS: We conducted a retrospective descriptive study using administrative claims data of outpatient prescribed non-opioid analgesics of the Swiss health insurance company Helsana between January 2014 and December 2019. First, we evaluated the number of claims and defined daily doses  per year of metamizole, ibuprofen, diclofenac and paracetamol in adults aged 18 years or over. Second, we characterised new users of these non-opioid analgesics in terms of sex, age, claimed comedications and canton of residence.

RESULTS: From 2014 to 2019, among the investigated non-opioid analgesics, metamizole showed the highest increase in claims (+9545 claims, +50%) and defined daily doses (+86,869 defined daily doses, +84%) per 100,000 adults. Metamizole users had the highest median age (62 years [IQR: 44–77]) compared to ibuprofen (47 years [IQR: 33–62]), diclofenac (57 years [IQR: 43–71]) and paracetamol (58 years [IQR: 39–75]) users. Metamizole users also more frequently claimed proton pump inhibitors, anticoagulants, platelet aggregation inhibitors and antihypertensive drugs than users of other non-opioid analgesics. While metamizole was most frequently claimed in German-speaking regions of Switzerland, ibuprofen and paracetamol were most frequently claimed in the French-speaking regions and diclofenac in German- and Italian-speaking regions.

CONCLUSION: In Switzerland, metamizole was increasingly claimed between 2014 and 2019. Metamizole was most frequently claimed by older adults and patients with comedications suggestive of underlying conditions, which can be worsened or caused by use of nonsteroidal anti-inflammatory drugs. The lack of studies regarding the effectiveness and safety of metamizole in this population warrants further investigation.

References

  1. Lutz M. Metamizole (Dipyrone) and the Liver: A Review of the Literature. J Clin Pharmacol. 2019 Nov;59(11):1433–42. 10.1002/jcph.1512 DOI: https://doi.org/10.1002/jcph.1512
  2. The International Agranulocytosis and Aplastic Anemia Study, Risks of Agranulocytosis and Aplastic Anemia. JAMA. 1986 Oct;256(13):1749. 10.1001/jama.1986.03380130077032 DOI: https://doi.org/10.1001/jama.1986.03380130077032
  3. Ibáñez L, Vidal X, Ballarín E, Laporte JR. Agranulocytosis associated with dipyrone (metamizol). Eur J Clin Pharmacol. 2005 Jan;60(11):821–9. 10.1007/s00228-004-0836-y DOI: https://doi.org/10.1007/s00228-004-0836-y
  4. Shapiro S, Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Thamprasit T, et al.; Aplastic Anemia Study Group. Agranulocytosis in Bangkok, Thailand: a predominantly drug-induced disease with an unusually low incidence. Am J Trop Med Hyg. 1999 Apr;60(4):573–7. 10.4269/ajtmh.1999.60.573 DOI: https://doi.org/10.4269/ajtmh.1999.60.573
  5. 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 Feb;159(4):369–74. 10.1001/archinte.159.4.369 DOI: https://doi.org/10.1001/archinte.159.4.369
  6. Hamerschlak N, Maluf E, Biasi Cavalcanti A, Avezum Júnior A, Eluf-Neto J, Passeto Falcão R, et al. Incidence and risk factors for agranulocytosis in Latin American countries—the Latin Study: a multicenter study. Eur J Clin Pharmacol. 2008 Sep;64(9):921–9. 10.1007/s00228-008-0513-7 DOI: https://doi.org/10.1007/s00228-008-0513-7
  7. Huber M, Andersohn F, Sarganas G, Bronder E, Klimpel A, Thomae M, et al. Metamizole-induced agranulocytosis revisited: results from the prospective Berlin Case-Control Surveillance Study. Eur J Clin Pharmacol. 2015 Feb;71(2):219–27. 10.1007/s00228-014-1777-8 DOI: https://doi.org/10.1007/s00228-014-1777-8
  8. Maj S, Lis Y. The incidence of metamizole sodium-induced agranulocytosis in Poland. J Int Med Res. 2002;30(5):488–95. 10.1177/147323000203000504 DOI: https://doi.org/10.1177/147323000203000504
  9. 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(4):1374–80. 10.1177/147323001003800419 DOI: https://doi.org/10.1177/147323001003800419
  10. Lampl C, Likar R. Metamizol: Wirkmechanismen, Interaktionen und Agranulozytoserisiko. Schmerz. 2014 Dec;28(6):584–90. 10.1007/s00482-014-1490-7 DOI: https://doi.org/10.1007/s00482-014-1490-7
  11. Hedenmalm K, Spigset O. Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole). Eur J Clin Pharmacol. 2002 Jul;58(4):265–74. 10.1007/s00228-002-0465-2 DOI: https://doi.org/10.1007/s00228-002-0465-2
  12. 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 Feb;71(2):209–17. 10.1007/s00228-014-1781-z DOI: https://doi.org/10.1007/s00228-014-1781-z
  13. Huber M, Andersohn F, Bronder E, Klimpel A, Thomae M, Konzen C, et al. Drug-induced agranulocytosis in the Berlin case-control surveillance study. Eur J Clin Pharmacol. 2014 Mar;70(3):339–45. 10.1007/s00228-013-1618-1 DOI: https://doi.org/10.1007/s00228-013-1618-1
  14. Andrès E, Maloisel F. Idiosyncratic drug-induced agranulocytosis or acute neutropenia. Curr Opin Hematol. 2008 Jan;15(1):15–21. 10.1097/MOH.0b013e3282f15fb9 DOI: https://doi.org/10.1097/MOH.0b013e3282f15fb9
  15. European Medicines Agency. Metamizole: Risk of drug-induced liver injury, 2020. https://www.ema.europa.eu/en/medicines/dhpc/metamizole-risk-drug-induced-liver-injury
  16. Federal Institute for Drugs and Medical Devices. Direct Healthcare Professional Communication (DHPC) on metamizole: risk of drug-induced liver injury, 2020. https://www.bfarm.de/SharedDocs/Risikoinformationen/Pharmakovigilanz/EN/RHB/2020/rhb-metamizol.pdf?__blob=publicationFile/
  17. swissmedic, DHPC – Metamizol, 2021. https://www.swissmedic.ch/swissmedic/de/home/humanarzneimittel/marktueberwachung/health-professional-communication--hpc-/dhpc-metamizol.html (accessed Aug. 08, 2022).
  18. S.-A. (Suisse). Fachinformation Novalgin. https://www.swissmedicinfo.ch/
  19. Wertli MM, Reich O, Signorell A, Burgstaller JM, Steurer J, Held U. Changes over time in prescription practices of pain medications in Switzerland between 2006 and 2013: an analysis of insurance claims. BMC Health Serv Res. 2017 Feb;17(1):167. 10.1186/s12913-017-2086-6 DOI: https://doi.org/10.1186/s12913-017-2086-6
  20. Helsana, Arzneimittelreport. https://www.helsana.ch/de/helsana-gruppe/medien-publikationen/helsana-reports/arzneimittelreport.html
  21. Frechen S, Zoeller A, Ruberg K, Voltz R, Gaertner J. Drug interactions in dying patients: a retrospective analysis of hospice inpatients in Germany. Drug Saf. 2012 Sep;35(9):745–58. 10.2165/11631280-000000000-00000 10.1007/BF03261971 DOI: https://doi.org/10.1007/BF03261971
  22. Gaertner J, Ruberg K, Schlesiger G, Frechen S, Voltz R. Drug interactions in palliative care—it’s more than cytochrome P450. Palliat Med. 2012 Sep;26(6):813–25. 10.1177/0269216311412231 DOI: https://doi.org/10.1177/0269216311412231
  23. García Rodríguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994 Mar;343(8900):769–72. 10.1016/S0140-6736(94)91843-0 DOI: https://doi.org/10.1016/S0140-6736(94)91843-0
  24. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ. 2000 Nov;321(7270):1183–7. 10.1136/bmj.321.7270.1183 DOI: https://doi.org/10.1136/bmj.321.7270.1183
  25. Rostom A, Muir K, Dubé C, Jolicoeur E, Boucher M, Joyce J, et al. Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane Collaboration systematic review. Clin Gastroenterol Hepatol. 2007 Jul;5(7):818–28. 10.1016/j.cgh.2007.03.011 DOI: https://doi.org/10.1016/j.cgh.2007.03.011
  26. Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, et al.; Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013 Aug;382(9894):769–79. 10.1016/S0140-6736(13)60900-9 DOI: https://doi.org/10.1016/S0140-6736(13)60900-9
  27. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006 Jun;332(7553):1302–8. 10.1136/bmj.332.7553.1302 DOI: https://doi.org/10.1136/bmj.332.7553.1302
  28. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006 Oct;296(13):1633–44. 10.1001/jama.296.13.jrv60011 DOI: https://doi.org/10.1001/jama.296.13.jrv60011
  29. Helin-Salmivaara A, Virtanen A, Vesalainen R, Grönroos JM, Klaukka T, Idänpään-Heikkilä JE, et al. NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland. Eur Heart J. 2006 Jul;27(14):1657–63. 10.1093/eurheartj/ehl053 DOI: https://doi.org/10.1093/eurheartj/ehl053
  30. Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018 Sep;362:k3426. 10.1136/bmj.k3426 DOI: https://doi.org/10.1136/bmj.k3426
  31. Huerta C, Castellsague J, Varas-Lorenzo C, García Rodríguez LA. Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population. Am J Kidney Dis. 2005 Mar;45(3):531–9. 10.1053/j.ajkd.2004.12.005 DOI: https://doi.org/10.1053/j.ajkd.2004.12.005
  32. Harirforoosh S, Jamali F. Renal adverse effects of nonsteroidal anti-inflammatory drugs. Expert Opin Drug Saf. 2009 Nov;8(6):669–81. 10.1517/14740330903311023 DOI: https://doi.org/10.1517/14740330903311023
  33. R. Schneider, N. Schur, R. Daphne, S. Matthias, and C. R. Meier, Helsana Arzneimittelreport, 2017.
  34. Twerenbold S, et al. Helsana-Arzneimittelreport für die Schweiz 2021, 2021. Online. Available: https://reports.helsana.ch/arzneimittel2021/
  35. World Health Organization. Defined Daily Dose (DDD). https://www.who.int/tools/atc-ddd-toolkit/about-ddd
  36. Knecht B, Lohmüller J, Telschow C. Arzneiverordnungs-Report 2019. Berlin, Heidelberg: Springer Berlin Heidelberg; 2019. 10.1007/978-3-662-59046-1
  37. Fabbri LM, Ferrari R. Chronic disease in the elderly: back to the future of internal medicine. Breathe (Sheff). 2006;3(1):40–9. 10.1183/18106838.0301.40 DOI: https://doi.org/10.1183/18106838.0301.40
  38. Linjakumpu T, Hartikainen S, Klaukka T, Veijola J, Kivelä SL, Isoaho R. Use of medications and polypharmacy are increasing among the elderly. J Clin Epidemiol. 2002 Aug;55(8):809–17. 10.1016/S0895-4356(02)00411-0 DOI: https://doi.org/10.1016/S0895-4356(02)00411-0
  39. Tielleman T, Bujanda D, Cryer B. Epidemiology and Risk Factors for Upper Gastrointestinal Bleeding. Gastrointest Endosc Clin N Am. 2015 Jul;25(3):415–28. 10.1016/j.giec.2015.02.010 DOI: https://doi.org/10.1016/j.giec.2015.02.010
  40. Fick DM, et al.; By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019 Apr;67(4):674–94. 10.1111/jgs.15767 DOI: https://doi.org/10.1111/jgs.15767
  41. Pazan F, Weiß C, Wehling M. The FORTA List Fit forThe Aged, 2021. https://forta.umm.uni-heidelberg.de/
  42. Holt S, Schmiedl S, Thürmann PA. Potentially inappropriate medications in the elderly: the PRISCUS list. Dtsch Arztebl Int. 2010 Aug;107(31-32):543–51. 10.3238/arztebl.2010.0543 DOI: https://doi.org/10.3238/arztebl.2010.0543
  43. Lavan AH, Gallagher P, Parsons C, O’Mahony D. STOPPFrail (Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy): consensus validation. Age Ageing. 2017 Jul;46(4):600–7. 10.1093/ageing/afx005 DOI: https://doi.org/10.1093/ageing/afx005
  44. Saragiotto B, Machado G, Ferreira M, Pinheiro M, Abdel Shaheed C, Maher C. Paracetamol for low back pain (Review) SUMMARY OF FINDINGS FOR THE MAIN COMPARISON. Cochrane. 2016;(6):10–2. 10.1002/14651858.CD012230.www.cochranelibrary.com DOI: https://doi.org/10.1002/14651858.CD012230
  45. Leopoldino AO, Machado GC, Ferreira PH, Pinheiro MB, Day R, McLachlan AJ, et al. Paracetamol versus placebo for knee and hip osteoarthritis. Cochrane Database Syst Rev. 2019 Feb;2(2):CD013273. 10.1002/14651858.CD013273 DOI: https://doi.org/10.1002/14651858.CD013273
  46. Kamboj AK, Hoversten P, Leggett CL. Upper Gastrointestinal Bleeding: etiologies and Management. Mayo Clin Proc. 2019 Apr;94(4):697–703. 10.1016/j.mayocp.2019.01.022 DOI: https://doi.org/10.1016/j.mayocp.2019.01.022
  47. Sowers JR, White WB, Pitt B, Whelton A, Simon LS, Winer N, et al.; Celecoxib Rofecoxib Efficacy and Safety in Comorbidities Evaluation Trial (CRESCENT) Investigators. The Effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Arch Intern Med. 2005 Jan;165(2):161–8. 10.1001/archinte.165.2.161 DOI: https://doi.org/10.1001/archinte.165.2.161
  48. Gislason GH, Rasmussen JN, Abildstrom SZ, Schramm TK, Hansen ML, Fosbøl EL, et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med. 2009 Jan;169(2):141–9. 10.1001/archinternmed.2008.525 DOI: https://doi.org/10.1001/archinternmed.2008.525
  49. Long AN, Dagogo-Jack S. Comorbidities of diabetes and hypertension: mechanisms and approach to target organ protection. J Clin Hypertens (Greenwich). 2011 Apr;13(4):244–51. 10.1111/j.1751-7176.2011.00434.x DOI: https://doi.org/10.1111/j.1751-7176.2011.00434.x
  50. Brater DC. Renal effects of cyclooxygyenase-2-selective inhibitors. J Pain Symptom Manage. 2002 Apr;23(4 Suppl):S15–20. 10.1016/S0885-3924(02)00370-6 DOI: https://doi.org/10.1016/S0885-3924(02)00370-6
  51. Bundesamt für Statistik. Ständige Wohnbevölkerung nach Geschlecht und Altersklasse, definitive Jahresergebnisse, 2015-2020. https://www.bfs.admin.ch/bfs/de/home/statistiken/bevoelkerung/stand-entwicklung/alter-zivilstand-staatsangehoerigkeit.assetdetail.18344300.html
  52. Bundesamt für Statistik, Szenarien zur Bevölkerungsentwicklung der Schweiz und der Kantone 2020-2050. https://www.viz.bfs.admin.ch/assets/01/ga-01.03.01/de/index.html
  53. Hoffmann F, Schmiemann G. Pain medication in German nursing homes: a whole lot of metamizole. Pharmacoepidemiol Drug Saf. 2016 Jun;25(6):646–51. 10.1002/pds.3954 DOI: https://doi.org/10.1002/pds.3954
  54. EMA. Metamizole: Risk of drug-induced liver injury, 2020. https://www.ema.europa.eu/en/medicines/dhpc/metamizole-risk-drug-induced-liver-injury
  55. de Abajo FJ, Gil MJ, García Poza P, Bryant V, Oliva B, Timoner J, et al. Risk of nonfatal acute myocardial infarction associated with non-steroidal antiinflammatory drugs, non-narcotic analgesics and other drugs used in osteoarthritis: a nested case-control study. Pharmacoepidemiol Drug Saf. 2014 Nov;23(11):1128–38. 10.1002/pds.3617 DOI: https://doi.org/10.1002/pds.3617
  56. Blaser LS, Duthaler U, Bouitbir J, Leuppi-Taegtmeyer AB, Liakoni E, Dolf R, et al. Comparative Effects of Metamizole (Dipyrone) and Naproxen on Renal Function and Prostacyclin Synthesis in Salt-Depleted Healthy Subjects – A Randomized Controlled Parallel Group Study. Front Pharmacol. 2021 Sep;12(September):620635. 10.3389/fphar.2021.620635 DOI: https://doi.org/10.3389/fphar.2021.620635

Most read articles by the same author(s)

<< < 1 2