Interventions for Tuberculosis Control and Elimination 2002

quent adverse drug events are gastrointestinal (weight loss, nausea, vomiting),
421 central nervous system, 421 and cutaneous adverse drug events. 435
An international investigation in 13 countries into adverse drug events due
to thioacetazone was coordinated by the British Medical Research
Council. 439 The frequency of adverse drug events in that study was 21%
compared to eight per cent of patients who were not receiving thioacetazone.
More than half of the adverse drug events were mild. The study
confirmed earlier observations that gastrointestinal and neurologic adverse
drug events (headache, blurred vision, perioral numbness, mental symptoms,
and peripheral nerve symptoms) were the most frequent, followed by cutaneous
adverse drug events. Two out of 1,000 patients developed agranulocytosis.
439 The frequency of adverse cutaneous reactions varied in different
populations. Differences in nutrition may be a contributor to this
observation as, for example, consumption of cheese and fish appear to
increase the risk of cutaneous and neurologic adverse drug events. 440
It was recognized relatively early that patients with HIV infection
have increased susceptibility to developing toxic epidermal necrolysis when
given sulfur-containing medications such as sulfadoxine 441 or sulfamethoxazole.
442 The causal relationship between the occurrence of cutaneous
adverse reactions and the use of thioacetazone has been elegantly
demonstrated (figure 27). 443 Reactions may present as pruritus without
rash, rash without epidermolysis, and most seriously as toxic epidermal
necrolysis. 444 The latter has a case fatality rate of 20% to 30%, depending
on the selection of cases (figure 28). Both reactions and deaths occur
relatively early in the course of administration, with more than half occur-
Table 7. Summary of adverse reactions from thioacetazone with estimated frequencies
of occurrence. Note that these are estimates of frequencies, which may
vary across population groups.
Frequent Common Infrequent Rare
(� 5 per 100) (� 1 per 100 and (� 1 per 1,000 (< 1 per 1,000)
< 5 per 100) and < 1 per 100)
Weight loss Toxic epidermal Toxic epidermal Agranulocytosis
Nausea necrolysis necrolysis
Vomiting (in HIV) (in non HIV)
Itching infected patients) infected patients)
Mental disturbances
Headache
Blurred vision
Perioral numbness
47