Epidemiology

Pyrazinamide more toxic than expected in treatment of TB

Last Updated: 2003-06-06 15:19:48 -0400 (Reuters Health)

NEW YORK (Reuters Health) - The incidence of major adverse reactions to the antituberculosis drug pyrazinamide (PZA) is higher than for other first-line agents, results of a study conducted at the Montreal Chest Institute in Quebec suggest.

According to Dr. Dick Menzies and associates, authoritative treatment guidelines suggest that addition of PZA to isoniazid and rifampin is not associated with a significant increase in hepatotoxicity. Because serious adverse reactions are associated with prolonged therapy, higher risk of hospitalization and increased treatment costs, they examined the medical records of 430 patients treated between 1990 and 1999.

There were 46 adverse events that resulted in treatment modification or hospitalization. Twenty-one patients developed rash and/or drug fever, while 12 patients developed drug-induced hepatitis. There were also 11 instances of severe GI upset, and 1 each of visual toxicity and arthralgia.

The incidence of major adverse effects was 1.48 per 100 person-months of exposure to PZA, an incidence higher than that observed in randomized trials, the Canadian investigators report. Corresponding rates were 0.49 for isoniazid, 0.43 for rifampin, and 0.07 for ethambutol.

Average duration of therapy was 380 days for patients with serious adverse reactions compared with 228 days for the other subjects. The number of visits to healthcare professionals was also increased among patients with serious adverse reactions.

Female gender, HIV infection, older age and birth in Asia were associated with greater risk.

These findings are "noteworthy and sobering," Dr. Richard E. Chaisson, of Johns Hopkins University School of Medicine in Baltimore, comments in an accompanying editorial. He suggests that they are of particular concern because "in most parts of the world, tuberculosis treatment is given with little or no clinical supervision."

"Although modern tuberculosis therapy is indeed miraculous," he writes, "it is not good enough." Despite the efficacy and low cost of currently available TB drugs, there is a critical need for the development of new agents.

Am J Respir Crit Care Med 2003;167:1461-1462,1472-1477.