Tolerance of pyrazinamide in short course chemotherapy for pulmonary tuberculosis in children

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Abstract
This prospective study was performed to evaluate the tolerance of pyrazinamide in short course chemotherapy in children. A total of 114 children ages 6 months to 15 years (4.5 ± 3.4 years) with diagnosed pulmonary tuberculosis from 1985 to 1995 entered the trial. A 2-month regimen of isoniazid, rifampin and pyrazinamide, followed by rifampin and isoniazid for the remaining 4 months, was administered orally to all children. Clinical adverse effects specifically investigated were gastrointestinal disturbances, rash, signs of hepatotoxicity and arthralgias. Laboratory toxicity data (number of leukocytes, erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase and serum uric acid) were collected before treatment and 1, 3 and 5 months after the beginning of chemotherapy. Clinical adverse effects were mild in all cases. Three children (2.6%) had fever and 5 (4.4%) had gastrointestinal disturbances. Aspartate aminotransferase and alanine aminotransferase mean values showed no differences along time and no patients had clinical signs of hepatotoxicity. Only 11 children (19.6%) showed a slight increase in alanine aminotransferase (<194 units/l). Serum uric acid increased in 92.2% of the children compared with pretreatment values. This increase remained within the normal range in all but 9.8% of patients. There was a significant increase in uric acid mean concentrations after 1 month of therapy (from 3.7 ± 0.7 mg/dl to 5.7 ± 1.6 mg/dl, P < 0.05), which fell again (4.0 ± 1.1) 1 month after pyrazinamide was stopped. There were no signs of gout or arthralgias. In no case was the treatment interrupted. The addition of pyrazinamide in chemotherapy for pulmonary tuberculosis in children was found to be safe. The slight increase in uric acid concentration during its administration had no recognized adverse consequences.