Introduction - Uppsala Monitoring Centre

apnoea in young children and with sudden infant death syndrome (SIDS)
(Kahn & Blum, 1979, 1982). Studies were carried out subsequently, although
they have not established a causal relationship (WHO, 2003).
SED 1952, 1960, 1963, SED 1980, SED 1984, SED 1988, SED 1992 and
SED 1996: not mentioned
Restrictions: should not be used in children below the age of one year, having
regard to their possible association with sudden infant death syndrome (WHO,
2003). Warning in the USA in 2005 against use in children under two years of
age, the EEC advised in 1991 that they should not be used for children under
the age on one year. Switzerland made it prescription only in 1990. In
Germany (1987), they were not to be used during pregnancy because of the
possibility of pyloric stenosis. Oman said in 2005 that promethazine was
contraindicated in children under two years of age.
Availability: as a cough medicine in Belgium, Netherlands, Brazil, Israel, France
and Switzerland (Martindale).
Drug Lifespan: 50 years
Delay in recognition: 42 years
Delay in regulatory action: 8 years
Time span of restrictions: one year
Comment: in France BIAM advises that it should not be given to children under
one year of age if there is a family history of SIDS.
1938 Diethylstilboestrol (DES) (Distilbene)
Use: prevention of miscarriage since 1941. Approved by the FDA on September
19 th 1941 for four indications: gonorrheal vaginitis, atrophic vaginitis,
menopausal symptoms and postpartum lactation suppression. On July 1 st
1947, the FDA approved the first supplemental New Drug Application (by
Squibb)) adding prevention of miscarriage.
ADR: identified as a carcinogen in animals (adenocarcinoma of the breast in
male mice) in 1938. NB before approval (Lacassagne, 1938). Known to have
no therapeutic value in pregnant women (Dieckmann et al., 1953).
Adenocarcinoma of the vagina in offspring discovered in 1970 by a casecontrol
study (Herbst et al., 1970; Herbst et al., 1971). A study in a special
registry found maternal exposure in 49 cases out of 66 cases of clear-cell
cancers of the genital tract (Herbst et al., 1972). Labelled by the FDA 5
months later, by the Netherlands in 1972 and in France in 1977; the UK
advised against its use in pregnancy in 1973 (Plamlund, 1993). The estimated
tumour risk is 0.14–1.4 per 1000 DES-exposed subjects, but since up to 6
million persons were exposed in utero to DES between 1940 and 1970 the
total number may be very high indeed (Dukes, 2000). There was also an
increased risk of breast cancer in DES mothers (relative risk >2) (Giusti et al.,