Introduction - Uppsala Monitoring Centre

1915).
SED 1952: methaemoglobinaemia, No mention of renal problems.
The hypothesis that analgesic drugs containing Phenacetin can cause
chronic renal disease was first mooted in 1953. They had noticed that
women working in Swiss watch factories took large amounts of analgesic
drugs because of occupational aches and pains (Spühler & Zollinger, 1953).
SED 1957: interstitial nephritis reported in 18 patients
SED 1958: renal insufficiency due to chronic interstitial nephritis (Schweiz
Med Wschr, 1956)
In 1959 a cross sectional study of 698 inpatients showed a significant
correlation between impaired renal function and the dosage and duration of
Phenacetin use (Larsen & Moller, 1959; Venning, 1983).
SED 1967: Prescott said ‘ nephrotoxicity has not been convincingly
demonstrated in respect of phenacetin and since other potentially
nephrotoxic drugs are always taken together with it. ‘Analgesic
nephrotoxicity’ is a more accurate term.’
In 1969 it was reported that it could also cause carcinoma of the renal pelvis
(Angervall et al., 1969).
In 1970 Koutsaimanis and Wardener said that it was only Phenacetin that
caused renal papillary necrosis (Koutsaimanis & Wardener, 1970), but this
was disputed by Prescott (Prescott, 1970). The number of UK fatal reports
between 1964 and 1980 was 105 and the rate per million of generalpractitioner
prescriptions was 1.6 (approximately) (Venning I, 1983).
A multicentre case-control study concluded that Phenacetin may increase the
risk of chronic renal disease and that its metabolite paracetamol
(acetaminophen) was also associated with an increased risk (Sandler et al.,
1989).
In 1991 it was shown in an epidemiological study in Switzerland that
Phenacetin caused an increased risk of hypertension, cardiovascular
disease, and mortality due to cancer, urological and renal disease; and that
the relative risk of death was 2.2 times that of the control group (Dubach et
al., 1991). Stolley referred to the lack of histopathological observations in
analgesic nephropathy which he thought was due to the late onset of renal
failure and therefore by the time a biopsy was done the scarring had so
distorted the histology as to make it unclassifiable (Stolley, 1991). Kracke
first mentioned Phenacetin as a possible cause of agranulocytosis in 1931
(Kracke, 1931). In Meyler’s 14 th edition it says ‘despite withdrawal of
phenacetin from the market, analgesic nephropathy has since continued to
appear.’ (Frie, 2000). The incidence of analgesic nephropathy (AN) shows
remarkable geographic variation: in Australia addiction to analgesics is more
common in Queensland and New South Wales which has been attributed to