Introduction - Uppsala Monitoring Centre

1952 Tetracycline paediatric (Achromycin V)
Use: an antibiotic
ADR: teeth discolouration, temporary inhibition of growth and enamel hypoplasia
(Van der Linden, 1965).
SED 1958 and SED 1963: no mention
SED 1966: some discolouration of the teeth
Withdrawn: in Jordan in 1973, Peru in 1974 (restricted), Italy in 1975
(suppositories only), the Philippines and the USA in 1978, Ghana in 1980,
Argentina in 1981, Bangladesh and Sudan in 1982, India in 1983, Oman in
1985, Pakistan in 1988, Chile in 1990 (warning), Nepal in 1991, also in
Australia, Belgium (warning), New Zealand and Saudi Arabia, United Arab
Emirates, Austria and Spain. The doctors were warned not to prescribe the
formulations to pregnant women or children under 9 years of age. HAI:
banned in 13 countries and restricted in five.
Availability: in the UK allowed in children over the age of 12 years and in the
USA in children over 8 years
Drug Lifespan: 21 years
Delay in recognition: 13 years
Delay in regulatory action: 8 years
Time span of restrictions: 18 years
Comment: an example of restriction of a particular formulation
1952 Coralgil (MG345, Trimanyl, Koralgil, Diaethiphenum), (4,4’ diethylaminoethoxy hexestral
dihydrochloride) is closely related to Triparanol (MER-29)
Use: coronary vasodilator and in 1964 as a cholesterol lowering drug.
ADR:’foam cell syndrome’ and phospholipidosis’ (these diseases are now called
‘Non-alcoholic steatohepatitis’) found in 1961 (Phillips & Avigan, 1961) leading
to liver cirrhosis and death. Estimated 50,000 victims and 250 deaths.
Lipidosis had been produced in rats and other experimental animals (Blohm,
1978). The information provided by the drug firm was misleading in several
ways: a higher dosage, rarely prescribed in other countries. Periodical
suspension was not in the instructions in Japan, but was in other countries;
unapproved claims such as ‘hypocholesterolemic action’ were used, which
was not mentioned in the drug insert (Hama, 1980).
SED 1960, SED 1963, SED 1966 and SED 1968: no mention.
Withdrawn: Japan in December 1969
Availability: none
Drug Lifespan: 17 years
Delay in recognition: 9 years
Delay in regulatory action: one month (Nakamura & Kawwamura, 1980)
Comment: possibly it was marketed only in Japan.