Introduction - Uppsala Monitoring Centre

Bismuth itself was in use in Roman times and spoken of by Paracelsus. Bismuth
subnitrate was created in 1748-1817 and bismuth subcarbonate in 1857. The other
insoluble salts are the subsalicylate, subcitrate and subgallate.
Use: used since 1733 as a medicinal salve and later in the 1920s for syphilis and
amoebiasis. Also used as an antacid and as a treatment for diarrhoea.
ADR: 1881 Bismuth subnitrate can cause vomiting, colicky pains, diarrhoea, a
sensation of heat, headache, dizziness and general debility (Lewin, 1881). In
1972 a colostomy association warned the Australian Adverse Drug Reactions
Advisory Committee (ADRAC) that there was a possibility that bismuth
subgallate powder was causing a neurological condition which is now known
as reversible myoclonic encephalopathy (symptoms: malaise, dysaesthesiae,
loss of memory, tremor, acute confusion, myoclonus, severe ataxia and
dysarthria) and the first report was by Burns et al. in 1974, when he reported
on treatment with bismuth subgallate in five Australian cases, where it was
used for colostomy patients to reduce the odour and flatulence and to improve
the consistency of their motions. ‘Reversible encephalopathy’ was once a
problem in some countries, notably France and Australia; bone and joint
toxicity had also occurred, sometimes associated with the encephalopathy.
This led to restrictions on the use of bismuth salts and a virtual disappearance
of these toxic effects (Burns et al., 1974). There were another 24 similar cases
in Australia that year (ADEC, 1974). At the same time in France there were
942 cases with 72 deaths (Martin-Bouyer, 1999). First described in 1973 in
French journals (Besle, 1975). In France there was an uneven geographical
distribution within France spreading from the Loire Atlantique region and Paris
eastwards and south across the country (Le Quesne, 1981) A single bismuth
injection for stomatitis caused death (J Belge, 1956). No cases had been
reported in the UK or the USA, where the subsalicylate and the subcitrate
were used. There were five cases in Switzerland with various salts, 6 cases in
Belgium, at least six cases in Spain and some cases in Germany following the
use of a cosmetic containing bismuth (Lagier, 1980). It was suggested that an
intestinal microorganism was able to convert the insoluble bismuth salt to an
absorbable form. It would seem to be dose-related with those with
encephalopathy having blood levels above 100µg/l whilst those taking similar
doses but not having encephalopathy having levels below 50µg/l (Le Quesne,
1981). Probable factors are: constipation, colostomies/ileostomies, prolonged
use and high doses.
SED 1952: CNS symptoms–insomnia, nervousness, parathesiae,
incoordination, tetanic convulsions, paralysis, polyneuritis and coma
SED 1960: no mention
SED 1972: no mention
SED 1975: discolouration of teeth, parathesia, impairment of concentration