Introduction - Uppsala Monitoring Centre

e given it may be allowed back on the market. There seems to be no
reason why this should not apply to insoluble bismuth salts. Further reading:
KK Jain’s Drug-induced Neurological Disorders. Hogrefe & Huber Publishers
2001, 27–28.
1885 Urethane (ethyl carbamate). Trade Names: Pressyl, Surparine, Profenil.
Use: originally used as a hypnotic, but later, when combined with quinine, for
sclerosing varicose veins and for malaria: Urethane, an efficient soporific
remedy (Kühn, 1894). Urethane (dose 15 to 30 grains) is a mild and safe
hypnotic, suitable for children (Willcox, 1934). First introduced by
Schmiedeberg in 1885 (Schmiedeberg, 1885).
Urethane was found by Warburg in 1910 to inhibit cell division in sea urchins.
In 1943, clinical trials were started in the Royal Cancer Hospital. Later in 1946,
it was used for the treatment of chronic myeloid leukaemia and then for acute
neoplasia.
After 1943, many trials were carried out with it, but by 1950 it had virtually
fallen out of use, superseded by the development of so many other
chemotherapeutic agents, whose discovery it had helped to stimulate
(MacGregor, 1966).
SED 1960: no mention
ADR: carcinogenicity [pulmonary adenomas in mice] (Nettleship et al., 1943).
There is inadequate evidence that urethane is carcinogenic in humans, but in
animals the evidence is considered to be sufficient (IARC vol 96, 2008).
Aplastic anaemia (6%), thrombocytopenia (14.5%), leucopenia (16%) and
cytolytic hepatic necrosis (Ohler et al., 1950) Agranulocytosis (Albahary,
1953).
SED 1952: leucopenia, thrombocytopenia and aplastic anaemia (Webster,
1947). ‘It has been virtually abandoned for therapeutic use as more efficient
tumour chemotherapeutic agents have been found.’ (Bonser, 1967).
Withdrawn: in Brazil and Canada in 1963, Cuba in 1964, Denmark in 1967,
Egypt, Japan and Thailand in 1973, the USA in 1977 (injection), Italy in 1979,
Greece in 1980, Germany in 1982 and France in 1985,
Availability: still available as an animal anaesthetic. Still used for multiple
myeloma in 1966 (Holland et al., 1966).
Drug Lifespan: 100 years
Delay in recognition: 59 years
Delay in regulatory action: 20 years
Time span of withdrawals: 22 years
Comment: it seems to have had four lives, the first as an hypnotic in humans,
second as an intravenous injection for varicose veins and malaria, thirdly as
an anti-cancer drug and the fourthly as an animal anaesthetic. One might