Introduction - Uppsala Monitoring Centre

SED 1960: addiction frequently observed with withdrawal symptoms. Other
overdose ADRs were: respiratory depression, hypotension, pulmonary
oedema, cerebral oedema, convulsions and sudden apnoea (BMJ Leader,
1976). The mortality from overdosage was 13.9% for glutethimide against
0.7% for barbiturates (Holland et al., 1975).
Withdrawn: its addiction liability and severity of withdrawal symptoms are equal
to those of the barbiturates and it is controlled under Schedule III of the 1971
Convention on Psychotropic Substances in UK. Withdrawn in Norway in 1980,
Zimbabwe in 1984, Pakistan in 1988, USA and France in 1991. Changed to
Schedule II in USA 1955.
Availability: not known
Drug Lifespan: 17 years.
Delay in recognition: 3 years
Delay in regulatory action: 26 years
Time span of withdrawals: 11 years
Comment: wide variation in times to regulatory action probably reflects differing
responses to drug dependence.
1955 Oxyphenisatin (Veripaque, Lavema, Noloc, Dialose, Protab)
Introduction first described in 1925. Dialose Plus consisted of: dioctyl sodium
sulfosuccinate, carboxymethylcellulose sodium and oxyphenisatin acetate.
Use: a laxative
ADR: chronic active hepatitis and cytolytic hepatitis. Mentioned in Physicians’
Desk Reference, 23 rd edition 1969 as idiosyncratic jaundice. The first case
with a positive rechallenge was in 1970 (McHardy & Balart, 1970; Reynolds
et al., 1970). Adequate animal toxicity studies had not been done. ‘The
sudden recognition of an association between an obvious symptom–
jaundice- and compounds such as …oxyphenisatin … which were said to
have been widely available for many years, was puzzling. This suggested
either a sudden increase in the usage of the drug and, therefore, in the
incidence of the reaction leading to its recognition or alternatively, recent
changes in formulation affecting toxicity.’ Investigations did not reveal any
formulation factor (ADEC, 1972).
SED 1964, SED 1966, SED 1968: no mention
SED 1984: despite the withdrawal of oxyphenisatin in many areas chronic
active hepatitis occurs from time to time as a result of its continued use.
Withdrawn: in Cuba in 1970; Australia and Japan in 1972; USA in 1973; Norway
in 1974; Denmark in 1975; Germany and Italy in 1976; Austria in 1977; the UK
and Canada in 1978; France in 1979, which was prompted by a French report
of six cases of chronic hepatitis (Delchier et al., 1979); Kuwait in 1980;
Belgium in 1981; Mauritius in 1982; Spain, Cyprus, Netherlands, New Zealand