Agranulocytosis Caused by Amidopyrine

Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole)

“…Several factors may influence the mortality associated with agranulocytosis, such as the causative drug, the general condition of the patient and the use of antibiotics and growth factors for granulocyte precursors in the treatment of agranulocytosis. In the pre-antibiotic era, the fatality rate was high, above 70% [6,7]. Following the introduction of antibiotics, reported case fatality rates have been consistently lower [8,9,10,11], approaching 8% in modern times [11].…”

“…Soon after, dipyrone was also identified as a cause of agranulocytosis, and cross sensitivity between dipyrone and amidopyrine was demonstrated [14]. Initially, the incidence of agranulocytosis was assumed to be the same for dipyrone as for amidopyrine [7], and the risk was suggested to be about 1 in 120 treated patients, an estimate which was based on potentially biased information from published and unpublished patient series [6,7]. However, the high magnitude of risk estimated for dipyrone has been questioned [15,16,17], and data from a large international case-control study, the International Agranulocytosis and Aplastic Anaemia (IAAA) study [15], suggest that the risk for agranulocytosis is as low as 1.1 cases per million users.…”

Epidemiological evaluation of rare side‐effects of mild analgesics.

“…Gsell & MUller (1950) observed no case of agranulocytosis in 220 patients treated with Irgapyrine (a combination of amidopyrine and phenylbutazone). Discombe (1952) interpreted as agranulocytosis two cases in this series in whom transient leukopenia was mentioned. Cermak found no cases of agranulocytosis.…”

“…One estimate of risk for amidopyrine-induced agranulocytosis is constantly cited in textbooks and by regulatory agencies (Huguley, 1964). Huguley's figures are based on calculations made by Discombe (1952) who had arbitrarily combined data from reports by Holten (1934), Rawls (1936) and Gsell & Muller (1950), as well as data from a personal communication by Cermak. The first two authors described five and four cases of agranulocytosis, in 352 and 400 patients treated with amidopyrine.…”

Drug-Induced Agranulocytosis

“…This magnitude of risk was never con-firmed, and even the relatively high estimates from Sweden (Bottiger & Westerholm 1973) amount to less than 5% of the widely quoted figures of Discombe (1952) and Huguley (1964). The results for some groups of drugs are shown in table III.…”