Introduction - Uppsala Monitoring Centre

generated in the stomach but it is widely considered that the trace amounts
are not relevant (WHO, 2003).
1896 Amidopyrine [US National Formulary]/aminopyrine, [BPC]/aminophenazone/pyramidone
(Cibalgin, Veramon, Pyramidon, Allonal, phenyldimethylamidopyrazolone)
A thesis dated 22 nd February 1897 said that experiments on dogs and guineapigs
was not able to establish the precise degree of toxicity in man and
supposed that doses of 8–10 grammes could be followed by most severe
results.
Use: analgesic and antipyretic
ADR: bone marrow suppression, agranulocytosis, renal damage, toxic epidermal
necrosis (Lyell’s syndrome) and Stevens-Johnson syndrome. Agranulocytosis
was reported with amidopyrine in 1933 (Madison and Squier, 1934), although
the first hint was given in 1931 (Kracke, 1931). A leader in the BMJ at the time
of the Discombe article said ’Amidopyrine became notorious as a cause of
agranulocytosis as long ago as 1922.’ (Leader, 1952), but I have been unable
to verify this statement. The relationship was finally established in 1935
(Kracke and Parker, 1935). Agranulocytosis–amidopyrine should be restricted
to patients having leukocyte counts several times a week (Hoffman et al.,
1934; Bohn, 1934; Silver, 1934).
SED 1952: agranulocytosis often occurs after use of compounds containing
aminopyrine. It is estimated that 50 patients annually die from agranulocytosis
after use of aminopyrine (Lancet 1951, 1, 389). Urticaria, purpura, skin
gangrene, albuminuria and optic nerve atrophy.
SED 1957 although agranulocytosis is observed (Gazz Int, 1954) it can cause
pancytopenia (Klin Wschr, 1954). The Committee on Safety of Drugs in its
annual report in 1966 said that the danger arises when it is given in excessive
doses over a long period and that special action was not necessary. It has
been suggested that aminopyrine and dipyrone are so similar that there is no
reason to suspect that they are not equally likely to produce agranulocytosis.
Therefore, an incidence of 0.79% or 1 in 126 for both drugs has been
estimated (Huguley, 1964). Others have estimated the figure as 1 in 10,000
(Dameshek & Colmes, 1936) whereas Discombe suggests that where
amidopyrine can be obtained freely an incidence of agranulocytosis between
2 and 5 per million may occur (Discombe, 1952). The IAAA study in 1986 did
not give figures for amidopyrine specifically, but gave a figure for other
pyrazolones which included aminopyrine multivariate rate ratio of 1.2 (CI 0.6-
2.5) compared with dipyrone 23.7 (CI 8.7–64.4) The estimates for
aminopyrine ‘lack validity’. (Levy, 1980). A meta-analysis of the IAAAS, a US
study and a Thailand study showed a relative risk of 1.4 (CI 0.6–3.2)
(Kaufman et al., 1996).