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LETTER TO THE EDITOR

Safe use of dipyrone

Chaparro, Luis Enriquea; Giraldo, Javier Mauriciob

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Colombian Journal of Anesthesiology (Revista Colombiana de Anestesiología): January-March 2020 - Volume 48 - Issue 1 - p 55-56
doi: 10.1097/CJ9.0000000000000144

As relates to the recently published Editorial of the Colombian Journal of Anesthesiology (Revista Colombiana de Anestesiología) entitled “Has the time come to restrict the clinical use of dipyrone?,”1 we agree with the author regarding the regulatory steps that must be adopted on the use not only of dipyrone but of the majority of analgesics sold over the counter. There is a need to put an end to the sale of those drugs without an adequate medical prescription based on the absence of risks for the individual patient and a rational time period for use.2

The safety profile of over-the-counter analgesics is difficult to ascertain; however, it has been found that the possibility of renal3 and gastrointestinal4 side-effects is more than 1%, while in some instances their use has been associated with increased cardiovascular risk5 and severe gastrointestinal bleeding.6 As has been reported by the most widely cited studies on pharmacovigilance and dipyrone, the incidence of agranulocytosis and aplastic anemia ranges between 0.5 and 2.7 cases for every million consumers.7 It appears that the incidence of agranulocytosis depends on genetic factors and previous exposure to the medication, which explains the wide variation between studies in Latino8 and nordic populations.9

The incidence of dipyrone-associated agranulocytosis is so low that it almost always results in one case report, as is this case. However, risks associated with traditional, commonly used analgesics, are sometimes ignored, although many times they may be lethal.

Dipyrone has been shown to be as effective as traditional anti-inflammatory agents for the treatment of postoperative pain,10 renal colic,11 and headaches of all types.12,13 It is important to highlight that before the Food and Drug Administration (FDA) ban, dipyrone was one of the most popular analgesics in the United States market, with more than 40 commercial brands; the veto came at around the time (late 1960s and early 1970s) of the launch to the market of the anti-inflammatory agents still in use today.14 The same thing happened with the blackbox imposed on droperidol early in this century, when setrons came to the market.15 Although we would not want to argue causality, it is quite a regrettable coincidence.

It is highly probable that the close scrutiny to which dipyrone is subjected will not change and that countries that favor its use will continue to do so even as North America continues to refer to it by the derogatory name of “Mexican aspirin.”16

In short, we are aware of the risk of agranulocytosis associated with the use of dipyrone but, unfortunately, other options available in the market have not proven to be more effective and are far from being safer for our population. Finally, the mortality risk associated with the use of dipyrone is, in absolute terms, even lower than that of dying in a collision as we commute to work. Consequently, we should not be deprived of the possibility of the rational use of the drug, just like we should not be deprived of the possibility of driving safely to work.

References

1. Gómez-Duarte OG. Is it time to restrict the clinical use of dipyrone? Colombian Journal of Anesthesiology 2019;47:81–83.
2. Hersh E, Moore P, Ross G. Over-the-counter analgesics and antipyretics: a critical assessment. Clin Ther 2000;22:500–548.
3. Whelton A. Renal effects of over-the-counter analgesics. J Clin Pharmacol 1995;35:454–463.
4. Bjarnason I. Gastrointestinal safety of NSAIDs and over-the-counter analgesics. Int J Clin Pract Suppl 2013;67:37–42.
5. Chan AT, Manson JE, Albert CM, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation 2006;113:1578–1587.
6. Rodríguez LG, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994;343:769–772.
7. Benseñor IM. Dipyrone and blood dyscrasia revisited: “non-evidence based medicine”. Sao Paulo Med J 2005;123:99–100.
8. Hamerschlak N, Maluf E, Biasi Cavalcanti A, et al. Incidence and risk factors for agranulocytosis in Latin American countries—the Latin Study: a multicenter study. Eur J Clin Pharmacol 2008;64:921–929.
9. Hedenmalm K, Spigset O. Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole). Eur J Clin Pharmacol 2002;58:265–274.
10. Chaparro LE, Lezcano W, Álvarez HD, et al. Analgesic effectiveness of dipyrone (metamizol) for postoperative pain after herniorrhaphy: a randomized, double-blind, dose-response study. Pain Pract 2012;12:142–147.
11. Edwards JE, Meseguer F, Faura C, et al. Single dose dipyrone for acute renal colic pain. Cochrane Database Syst Rev 2002;4:CD003867.
12. De Souza Carvalho D, Barea LM, Kowacs PA, et al. Efficacy and tolerability of combined dipyrone, isometheptene and caffeine in the treatment of mild-to-moderate primary headache episodes. Expert Rev Neurother 2012;12:159–167.
13. Bigal ME, Bordini CA, Tepper SJ, et al. Intravenous dipyrone in the acute treatment of migraine without aura and migraine with aura: a randomized, double blind, placebo controlled study. Headache 2002;42:862–871.
14. [No authors listed]Risks of agranulocytosis, 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;256:1749–1757.
15. Habib AS, Gan TJ. Food and drug administration black box warning on the perioperative use of droperidol: a review of the cases. Anesth Analg 2003;96:1377–1379.
16. Hargis JB, La Russa VF, Redmond J, et al. Agranulocytosis associated with “mexican aspirin” (dipyrone): evidence for an autoimmune mechanism affecting multipotential hematopoietic progenitors. Am J Hematol 1989;31:213–215.

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