Introduction - Uppsala Monitoring Centre

delay before it was acknowledged by the AMA.
Delay in regulatory action: 17 years
Time span of restrictions: 22 years
Comment: again if a drug is left on the market for specific indications it is
impossible to police the generalised use in poorer countries. The three year
delay in recognition stimulated the American Medical Association (AMA) to set
up a blood dyscrasia registry, which no longer functions. Chloramphenicol
continued to be sanctioned as an eye medication and then in 1955 a case of
aplastic anaemia was said to be caused by the eye drops (Rosenthal &
Blackman, 1965) and after another paper (Fraunfelder et al., 1982) the sale of
the eye drops in the USA dropped by 80% over two years (Doona & Walsh,
1995). Between 1988 and 1995 A survey of in 400 UK general practices found
442,543 patients who had received a prescription for chloramphenicol eye
drops and of these there were three cases of serious haematological toxicity,
two of which were possibly caused by the drops. The authors said their use
seems to be safe (Lancaste et al., 1998). In the USA National Register there
were 23 cases and the eye drops were no longer used in the USA (Doona,
1998). The delay by the regulatory authorities revolves around the probable
incidence of the ADR. The risk/benefit ratio with such rarities depends on a
complex balance of cost, alternative drugs and the different acceptance of risk
between rich countries and poor countries.
1949 Phenylbutazone (Butazolidine, Butazone, BTZ)
Marketed in UK in 1951
Use: rheumatic arthritis, osteoarthritis, ankylosing spondylitis, gout, Reiter’s
disease, bone pain with Paget’s disease and secondary neoplasm, extensive
superficial thrombophlebitis, and prolapsed intervertebral disc.
ADR: agranulocytosis, aplastic anaemia, acute interstitial nephritis,
thrombocytopenic purpura, hepatic granulomas, hepatitis and cirrhosis, and
reactivation of peptic ulcers. ‘The problem was predicted from the structural
similarity to amidopyrine and other pyrazolones of known toxicity to bone
marrow.’ (Venning II, 1983). The first report of agranulocytosis was in 1952
(Medico-legal, 1952). There were 503 deaths. The first case of aplastic anaemia
reported in the English press was in 1953 (Leonard, 1953). Thrombocytopenic
purpura was first reported in 1952 (Stephens, 1952). There was a high incidence
of toxic effects–42% (Nassim & Pilkington, 1953).
SED 1952: neither of the butazones is mentioned
1955 the 23 rd case of death caused by phenylbutazone was reported. There
were 10 deaths from agranulocytosis, 3 from peptic ulcer and gastrointestinal
haemorrhage, 3 from exfoliative dermatitis, 2 from renal lesions, and 2 were
unclassified. There were single cases reported because of thrombocytopenic