Introduction - Uppsala Monitoring Centre

1959 Danthron (Chrysazin, Dantron, Fructimer, Dorbanex, Codalax)
Use: an anthraquinolone laxative (a bacterial mutagen)
ADR: the results of two chronic toxicity studies in rats, (Four out of 12 developed
adenocarcinoma of the large bowel) (Mori et al., 1985) and mice (four out of
17 developed hepatocellular carcinomas) (Mori et al., 1986), have shown that
administration of high doses is associated with the development of intestinal
and liver tumours (Patel et al., 1989; WHO, 2003). Animal intestinal
carcinogenicity (Anonymous, 1990). There is sufficient evidence for the
carcinogenicity of dantron in experimental animals (IARC vol 50, 1990).
SED 1984: no mention
SED 1992: bacterial mutagens seem capable of inducing intestinal tumour in
animals.
Withdrawn: in the USA, Norway, Denmark, Japan, and France in 1987; in Spain
in 1988, but reintroduced with restricted indications in 1989 in Canada and
Germany (1986) and then withdrawn in 1998. Norway in 1997, In the UK its
use was restricted to geriatric medicine and analgesic-induced constipation in
the terminally ill in 1987 and then restricted just to the terminally ill in 2000
(BNF, 1999), but mentioned as available on the NHS without any caveats in
1992. HAI: banned in 6 countries and restricted in one.
Availability: in Ireland, UK, New Zealand, Canada, Brazil, France, Chile, Mexico
and South Africa (Martindale). In the UK it is restricted to geriatrics, terminally
ill patients and patients with heart failure or coronary thrombosis (BNF, 1999).
Drug Lifespan: 28 years
Delay in recognition: 26 years
Delay in regulatory action: 2 years
Time span of withdrawals: 11 years
Comment: reasonably anticipated to be a human carcinogen. A class effect.
1959 Triparanol (MER-29)
‘The approval letter to Merrell stated that no review of the drug’s efficacy had been
undertaken’…’Associate Commissioner John Harvey would conclude that his
agency’s conditional approval of MER/29 in April 1960 was mistaken.‘(Waxman,
2003). Prior to approval it had been said that before we release this drug for general
distribution… the company should submit results of well controlled extensive clinical
studies in which the individuals have received the drug for periods of years.
Use: cholesterol lowering drug blocked the last step in cholesterol biosynthesis in
animals and man (Steinberg et al., 1961).
ADR: cataracts, impotency and baldness
SED 1960: no mention
SED 1963: withdrawn – hair loss, abnormal liver function tests, exfoliative
dermatitis and leucopenia