Interventions for Tuberculosis Control and Elimination 2002

Table 4. Summary of adverse reactions from pyrazinamide 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)
Arthralgias Nausea Hepatitis Sideroblastic anemia
Rash Lupus erythematosus
Nausea Convulsions
Photodermatitis
24 hours. 327 Thus, uric acid retention could be reduced by intermittent
administration.
Relatively frequent events include rash 200,328,329 and nausea. 200 Rarer
adverse drug events include sideroblastic anemia, 75,93 lupus erythematosus, 330
convulsions, 331 and photodermatitis. 332
Interactions
Effect of pyrazinamide potentiated: Allopurinol increases plasma concentrations
of pyrazinoic acid which is directly responsible for the inhibition
of renal urate secretion. 333 Therefore, pyrazinamide-induced arthralgias are
unresponsive to allopurinol.
Effect of pyrazinamide opposed: A potentially serious interaction may exist
with zidovudin, with combination treatment leading to barely detectable
pyrazinamide levels. 334 However, these findings have not been confirmed.
Effect of drug potentiated by pyrazinamide: None identified.
Effect of drug opposed by pyrazinamide: Pyrazinamide might antagonistically
affect the action of medications that have a uricosuric effect such as
acetylic salicylic acid, ascorbic acid, probenecid, and iodine containing radiocontrast
offering preparations. 335,336
Ethambutol
Discovery. The synthesis of ethambutol (figure 20) was reported in
1961. 337 Its excellent activity in vitro and in vivo against M. tuberculosis
was reported in the same year. 338-340
37