Introduction - Uppsala Monitoring Centre

James McDonagh, referring to Salavarsan, said ‘There is no drug,
which has not at some time or another given rise to toxic symptoms,
so differently constituted in each human frame.’ (Williams, 2009). He
seems to have been against the use of Salvarsan and in favour of
mercury treatment.
Prior to the introduction of Kharsivan, the English version of
Salvarsan, the UK Board of Trade tested it and published an official
report on the ‘Toxicology of Salvarsan’ (1 st April 1916). Animal
toxicology had been performed on white mice, white rats and rabbits.
The clinical details were given of the adverse effects and the
individual reports of deaths, but no statistics were given. (Wilcox &
Webster, 1916). There was no mention of any specific liver
problems.
An army captain reported (29 th April 1916) on the effects of 600
injections of Kharsivan. He stated that 72% of patients had no
adverse reactions. This important information on new drugs is rarely
given even today. He also gave percentages for the adverse effects:
headache in 17%; rigor in 5%; vomiting in 7%; diarrhoea in 10%;
transient albuminuria in 0.3%; Herxheimer’s 166 reaction in 2.3%, etc.
There were no reports of liver problems. This is the first report that I
have found that gives good statistics on ADRs and which gave that
information to prescribers (Lucey, 1916).
There was an outbreak of acute yellow atrophy in patients who
had been given neoarsphenamine benzoate for syphilis at a military
hospital near Cambridge. The same problem had occurred in
Germany and there had been two official reports in 1914 and 1917.
The Medical Research Committee appointed a ‘Special Committee
on the manufacture, biological testing and clinical administration of
Salvarsan and its substitutes’, which reported in 1922 that the most
probable cause was the toxicity of the organo-arsenical compounds.
‘The Committee hope that a plain statement of the rare fatalities and
other untoward effects known to occur after the use of arsenbenzol
preparations may encourage the communication to the Ministry of
Health of details concerning such accidents, for it is only in the light
of such information that investigation and measures with regard to
their prevention can be successfully undertaken.’ Shah says that this
was the forerunner to monitoring of adverse reactions (Shah, 2001).
However, in retrospect, it was probably viral hepatitis. The
166 Herxheimer’s reaction = transient immunological reaction commonly seen after treatment of syphilis and
attributed to the release of endotoxin like substances from dying microorganisms.