Introduction - Uppsala Monitoring Centre

SED 1960 and SED 1963: no mention of ADRs
Withdrawn: in Germany, Italy, Singapore, Hongkong, Domenica, France, UK,
USA and Canada in 1979; Australia, Egypt, Brazil, Panama and Philippines in
1980; Argentina in 1981; India in 1983; Oman in 1992; and also withdrawn in
Chile, New Zealand and Venezuela. HAI: banned in 19 countries.
Availability: on the internet
Drug Lifespan: 32 years
Delay in recognition: 32 years
Delay in regulatory action: Nil
Time span of withdrawals: 13 years
Comment: if a drug is left on the market for specific indications it is impossible to
police the generalised use in poorer countries.
1948 Chloramphenicol (Chloromycetin)
Was approved in the US on 12 th January 1949 and introduced in the UK in
August 1949.
Use: an antibiotic, which was originally tested for scrub typhus and now used for
typhoid, salmonella, meningitis and rickettsial infections (Sneader, 2005).
ADR: the presence of the nitrobenzene radical in the structure of
chloramphenicol led to the suspicion that the drug might be toxic to the
haemopoietic system (Smadel, 1949). Three patients showed marrow
hypoplasia after chloramphenicol with a positive dechallenge (Volini et al.,
1949). The first confirmation of this hypothesis was a single fatal case of
aplastic anaemia reported in 1950 (Rich et al., 1950) followed in 1952 by a
paper, authored by FDA staff, saying, ‘it appears beyond a reasonable doubt
that chloramphenicol, in certain susceptible individuals, causes blood
dyscrasias, including aplastic anaemia, thrombocytopenic purpura,
granulocytopenia and pancytopenia.’ This paper gave details of 19 articles on
the subject between 1949 and August 1952. The authors recommended a
change in labelling and that the drug should not used for minor infections
(Lewis et al., 1952). ‘In 1952 when it was realised that chloramphenicol had
caused scores of cases of aplastic anaemia and that it had taken three years
to appreciate the potential toxicity of the drug’. (Doll, 1969). In June 1952 the
number of cases of blood disorders associated with chloramphicol in the US
was 410, but in only 61 cases was the drug the only drug being taken. It was
suggested that a case control study should be undertaken but nothing was
done. The main problem, which is true with many drugs, was that doctors
misuse and over use antibiotics.
(Marks, http://www.hopkinsmedicine.org/histmed/images/hmadverse.pdf;
Maeder, 1994).
SED 1952: mentioned aplastic anaemia (12 cases) and agranulocytosis.