Introduction - Uppsala Monitoring Centre

In 1958 Garrod reported an approximate incidence of one case of aplastic
anaemia per 400 cases at St Bartholomew’s hospital (Garrod, 1958).
SED 1960: the sub-committee of the AMA Research Council–There were 27
certain cases, 30 probable cases and 7 possible cases of agranulocytosis.
US labelling had to include warnings of blood dyscrasias [topical preparations
excepted]. Between 1957 and 1961 there were 138 deaths caused by the
drug in California. The risk of fatal aplastic anaemia was at least 1:60,000
(Smick et al., 1964) or between 1 in 40,800 and 1 in 24,500 or 13 times the
background level (Wallerstein et al., 1969). Confirmation of causality came
when it was shown that reversible marrow suppression could be induced by
high dosage (Krakoff et al., 1975; Venning II, 1983).’Since the risk of serious
chloramphenicol toxicity is so small (1:18,000 or probably less) it is of more
than historical interest there are still many areas in which the benefits
outweigh its risks.’ (Ruef & Blaser, 2000). The use of chloramphenicol eye
drops lingered on despite a report in 1955 of a death from bone marrow
aplasia resulting from the eye drops (Rosenthal and Blackman, 1965; Doona
& Walsh, 1995), but it still remains on the UK market. The estimated risk
increased from 1:200,000 in 1951 to 1:20,000 in 1971 a ten-fold increase.
Tognoni said that chloramphenicol aplastic anaemia was rare in Southern
European countries (Tognoni, 1979). In Sweden there was a steady decline in
prescription of chloramphenicol after a warning was given in May 1968
(Böttiger & Westerholm, 1973). Chloramphenicol is possibly carcinogenic to
humans (IARC vol 50, 1990).
Restrictions: there was a UK regulatory warning in 1967 (Venning II, 1983) and
it was restricted to life threatening infections, particularly those caused by
haemophilus influenzae and for typhoid fever; also as an ingredient in ear and
eye drops (BNF, 1999). Its use was restricted in Germany and Japan
(indications restricted) in 1975; Denmark and France in 1978; Philippines in
1982, Egypt in 1983; Netherlands in 1984; Canada and Spain in 1985;
Hungary in 1987; Ireland in 1989, because of aplastic anaemia. It remained
on the USA and UK markets for Rocky Mountain Spotted fever in the former
and for haemophilus influenza infections and typhoid fever in the latter. In
Germany its use is restricted to cases of acute attacks of typhoid, paratyphoid
or purulent meningitis. It also has strict regulations in countries like Israel and
the Netherlands. In the USA the ‘detailmen continued to promote the drug as
effective for a wide range of uses, resulting in widespread use of the drug for
minor infections and an unnecessary toll of serious adverse reactions and
death.’ (Waxman, 2003).
Availability: still in wide usage including Indonesia.
Drug Lifespan: 19 years
Delay in recognition: approximately one year before the first papers, but then a