Introduction - Uppsala Monitoring Centre

Comment: a Lancet editorial entitled ‘Dipyrone hearing by the German Drug
Authority’ illustrates the problem of converting medical evidence into law:
’Political pressure, coupled with the manufacturer’s argument that the casecontrol
study would document the safety of the drug, prevented the BGA from
taking stronger measures–such as removing the drug from the market or even
having it put on prescription… The case of dipyrone is the most important
example of serious discrepancies in the standards of safety adopted by
different national drug regulatory authorities. These discrepancies seem to be
due to administrative and political differences rather than to differing standards
or competence.’ (Leader, 1986). Another editorial said that drugs such as
metamizole were perhaps unjustly deleted from our pharmacopoeia because
of imprecise studies of adverse side effect; some of the older therapeutic
agents such as metamizole may be identified as having clinical utility in
children (Berlin, 2001). The wide variation in the figures from the different
centres (Ulm, Berlin and Barcelona) with the multivariate rate ratio 23.7%
whilst for Israel and Budapest it was 0.8%) in this IAAA study suggests that
there are other factors at play which may be genetic (IAAAS 180 , 1986).
1928 Dioxide (Thorotrast)
Use: radioactive contrast medium containing Thorium
ADR: aplastic anaemia was induced in a rabbit by a large dose of thorium in
1931 (Lambin & Gerard, 1931) and leucopenia in rabbits in 1933 (Gottlieb,
1933) and in 1933 granulomas had been produced in animals (Jörg &
Aguirre, 1933). A comment in the BMJ stated that as thorium dioxide is
radioactive and that it was known that prolonged radio-activity was known to
result in cancer that there was a possibility that Thorotrast might give rise to
malignant disease (BMJ leader, 1935) Its carcinogenetic properties were
shown in animals in 1938 ‘Because of the ultimate danger of malignancy,
radio-active substances such as thorotrast should never be introduced into
the human body, all the more so since there are other non-toxic radioopaque
substances.’ (Selbie, 1938). A case of aplastic anaemia due to
Thorotrast was reported in 1946 (Spier et al., 1947). Acute leukaemia (Artzl
Forsch, 1955), pancytopenia, myelofibrosis and also caused liver cirrhosis,
hepatocellular carcinomas, intrahepatic cholangiocarcinomas and
haemangioendotheliomas of the liver and other tumours. The induction period
was from 6 years to 35 years (Bonser, 1967). Its radioactivity consisted almost
entirely of very short-range alpha particles with negligible gamma radiation
(Jellinek, 2004). It had a half-life of 400 years. It was shown to produce
subcutaneous sarcomas in rats and mice in 1938 (Anon, 1938). There were
180 IAAAS = International Agranulocytosis and Aplastic Anaemia Study