Introduction - Uppsala Monitoring Centre

Delay in recognition: None
Delay in regulatory action: 29 years
Time span of withdrawals: 12 years
Comment: the problem was finding whether there were sulphonamides that
were better than sulfathiazole and it is probable that that caused the delay in
withdrawal. Aplastic anaemia, agranulocytosis and thrombocytopenias are
sulphonamide class effects (Albahary, 1953).
1944 Di-hydro-streptomycin sulphate
Use: an antibiotic.
ADR: neuropsychiatric problems and ototoxicity. ‘Di-hydro-streptomycin is more
toxic than streptomycin.’ (Minkenhet, 1950). Clinically the toxicity of di-hydrostreptomycin
is much more significant, since it may easily cause partial or
complete loss of hearing, whereas streptomycin tends to affect only the
vestibular apparatus (Ruef & Blaser, 2000).
SED 1952: some investigators are of the opinion that the toxicity for the
vestibular and cochlear nerves is greater after prolonged use of
dihydrostreptomycin than is the case with streptomycin (no reference was
given).
Withdrawn: in the USA in 1970, Philippines in 1972, Spain in 1983 and also in
Dominica and Italy. HAI: banned in 6 countries.
Availability: in Belgium, Poland, Mexico, Portugal, Philippines, Australia, Greece
and Ireland (Martindale).
Drug Lifespan: 26 years
Delay in recognition: ≤ 8 years
Delay in regulatory action: ≥ 18 years
Time span of withdrawals: 13 years
Comment: I haven’t found a paper which reports on a comparison between the
two streptomycins. It was his deafness caused by di-hydro-streptomycin that
prompted Leopold Meyler to write his famous textbook ‘The Side Effects of
Drugs’.
1947 Methapyrilene (Rinofol, Thenylene, Histadyl, Nytol)
Use: a type 1 antihistamine
ADR: produced hepatocellular carcinomas and cholangiocarcinomas in rats
(Lijinsky et al., 1980). This was confirmed in 2000 (Cunningham, 2000).
Fatalities occurred on over dosage (Winek et al., 1977). It was banned
because it could cause liver tumours in rats if given 25 to 30 times the normal
human dose throughout the animal’s normal lifespan (Lewis, 1979).
SED 1952: one fatal case in a 16 month child: anuria, cerebral oedema,
nephrosis and toxic psychosis (Rives et al., 1949).