Introduction - Uppsala Monitoring Centre

and acuity, dementia, inability to walk, psychoses, hallucinations and
convulsions were all reported in France with bismuth sub-nitrate
Withdrawn: bismuth subgallate was withdrawn in Egypt and became prescription
only in Japan in 1975. It was used only in suppository form in Saudi Arabia. It
was withdrawn in Greece in 1976. All insoluble salts were suspended in
France in 1978 and withdrawn in Austria in 1980. They were banned in
Bangladesh and withdrawn in Turkey (except colloidal bismuth K citrate
complex) and in Mauritius in 1982. In Cuba bismuth sub-nitrate was prohibited
for children. In Sweden they became prescription only products and in Oman
antidiarrhoeal preparations containing bismuth were prohibited in 1989. India
prohibited their manufacture and sale. Italy warned of prolonged use and high
dosage, because of reversible myoclonic encephalopathy. There is restricted
usage in the USA–subsalicylate and subcitrate. Health Action International
(HAI): banned in 7 and restricted in seven.
Availability: Spain, Mexico, Brazil, Argentina, Germany, USA, Netherlands and
South Africa (Martindale). The salts available are: subgallate, subsalicylate,
aluminate, subcitrate, oxide, subnitrate, salicylate and subcarbonate. The
subgallate is registered in Sri Lanka, Malaysia and Thailand where other
bismuth products are also available. Bismuth products are also available in
Korea and Thailand (HAI, 2008). The subgallate is available in the UK in
suppositories and as an anal ointment–Anusol. Bismuth is still used as
antacid (BNF, 1999). Bismuth subsalicylate (Pepto-Bismol 525 mgm q.d.s 179 )
is a recommended treatment for traveller’s diarrhoea (Hill & Ryan, 2008). It
remains an over-the-counter (OTC) product in many parts of the world.
Drug Lifespan: 100 years
Delay in recognition: 99 years probably because an unknown factor was not
present until the early 1970s.
Delay in regulatory action: 1 year
Time span of withdrawals: 14 years
Comment: there has been a wide variation in the reports from different
countries. There were no cases in the UK, but the cases were seen
predominantly in France and Australia. The subgallate was the main bismuth
product available in Australia and the subnitrate in France. Quite how the
previously insoluble salts became soluble enough to be absorbed and reach
the brain is not certain. The known factors are: adult, elderly, colonopathy
with chronic constipation, colostomy or ileostomy and female (Manigand,
1982). The first action taken after the recognition of a serious ADR may be
to withdraw it; but once the causative factors are known and warnings can
179 Q.D.S. = quater die sumendus = four times a day