Introduction - Uppsala Monitoring Centre

eport of optic atrophy leading to blindness. By October 1967, 1,452 cases
had been reported and this had increased to 1,653 in 1968, to 2,892 by 1969
and to 7,856 by October 1970. The Japanese undertook an investigation in
1968 and concluded that the drug was the cause in August 1970 (Tsubaki et
al., 1971) and promptly removed the drug from the market with 186 other
halogenated hydroxy-quinolones (Cobert & Biron, 2002). Between 1956 and
1970, there were 10,000 cases of SMON in Japan (Oakley, 1980).
SED 1952: Vioform: agranulocytosis
SED 1960; SED 1963; SED 1966; and SED 1968: no mention ADRs
Withdrawn: FDA stopped OTC products in 1961. withdrawn in Japan on 8th
September 1970, warning given in Australia in 1971, Withdrawn in the USA in
1973, Norway in 1974, Sweden in 1975, Belgium in 1976, Germany in 1977,
Denmark in 1978, France, Argentina and UK in 1981, Nigeria, Philippines and
Bangladesh in 1982, Canada, Italy, Nepal, Dominica, Zambia and Spain in
1983, Hongkong and Ethiopia in 1984, Honduras in 1985, Oman in 1987,
Pakistan in 1988, Ghana in 1989, Libya in 1990, also in Bahrain, Cuba,
Switzerland, Netherlands, Saudi Arabia, Congo, Thailand, Malaysia, Taiwan,
and Venezuela, because of subacute myelo-optic neuropathy (SMON). There
are many paradoxes: greater use in Indonesia but no epidemic there, retained
in India where the disease is rare (Mann, 1986). The role of clioquinol in
SMON was not recognised before 1965 when they considered the possibility
of infection and allergy, but they noted that it occurred one week or so after
the abdominal symptoms, which included diarrhoea (Tsubaki et al., 1965).
Australia and Venezuela restricted its use to amoebic dysentery and
acrodermatitis enteropathica (Scrip, 1983). HAI: banned it in 23 countries and
restricted in three.
Availability: in 1993 in 39 countries including India, Indonesia, Thailand, the
Middle East, Egypt, Mexico, Central America, Columbia, Venezuela, Brazil
and New Zealand (prescription only) (Drug labelling in developing countries,
1993). Available in the UK as eardrops and as an ingredient in skin
preparations – Vioform hydrocortisone (BNF, 1999).
Drug Lifespan: 41 years
Delay in recognition: 36 years
Delay in regulatory action: one month after the SMON Research committee
reported.
Time span of withdrawals: 20 years
Comment: the two possible causes were a virus infection and clioquinol. An
infectious aetiology is consistent with evidence of seasonal variation in
incidence and the clustering of cases in families, institutions, doctors and
hospitals. Animal studies suggested that it was a new neuropathic slow virus
causing pathological changes including spongy degeneration of the brain