Introduction - Uppsala Monitoring Centre

1995).
SED 1952: the same side effects as other synthetic substances with an
oestrogenic effect
‘However, one is still uncertain concerning the harmlessness of such
quantities of drugs on the product of conception, and more especially on its
gonadic functions.’ (Albahary, 1953).
SED 1960: no mention
SED 1968 (VI) it also causes hepatocellular carcinoma in males.
Withdrawn: FDA banned its use in pregnant women in 1971. It was withdrawn in
Panama in 1973, the USA, Netherlands and Australia in 1975, Germany and
Austria in 1977, Greece and Kuwait in 1980, Tunisia in 1983, France and
Japan in 1997, Spain and Belgium in 1983, also in Italy and Saudi Arabia. In
Australia, Greece and Germany, its use is permitted only for the treatment of
prostate cancer.
Availability: diethylstilboestrol remains available in many countries; however,
only for the treatment of certain hormone-dependent neoplasms including
carcinoma of the prostate and postmenopausal breast cancer (WHO, 2003).
Last documented prescription was in Spain in 1983. (Direcks et al.,1991). In
the UK it is still used, but rarely, for breast cancer and prostate cancer (BNF,
1999).
Drug Lifespan: 33 years
Delay in recognition: 33 years
Delay in regulatory action: 3 years
Time span of withdrawals: 12 years
Comment: it was the first drug submitted to the FDA after the 1938 Food, Drugs
and Cosmetic Act although it had already been identified as a carcinogen.
This, plus its lack of efficacy for its intended purpose, which was only
discovered in the 1950s, should have prevented its marketing. A
pharmacovigilance disaster.
1940 Pyrithyldione/diphenhydramine (Dorma; Persedon, Benedorm, diprilone,
dihydropyridine)
Use: a sedative/hypnotic
ADR: a case of agranulocytosis was reported in 1949 in the USA (Tyson, 1949)
and there were anecdotal cases from the 1960s and 1970s in Germany and
from the 1980s in Japan (Ibáñez et al., 2000). Leucopenia had been reported
in rabbits in 1940.
SED 1952: agranulocytosis
In Spain between 1980 and 1995, the Pharmacovigilance Centre of the
Catalan Institute of Pharmacology received some 280 reports of
agranulocytosis. Of these, nine were associated with use of a combination