Aging and hepatotoxicity of isoniazid and rifampin in pulmonary tuberculosis.

Abstract

We evaluated whether elderly patients with pulmonary tuberculosis and without apparent preexisting liver disease are at an increased risk to develop hepatotoxicity from an isoniazid-rifampin regimen and require regular liver function tests in comparison with younger patients. We analyzed the data of 131 patients treated in the period 1980-1985 of whom 64 (49%) were at least 60 yr of age. Subsequent increases of transaminases (measured weekly for as long as 4 wk after the start of treatment and later on when symptoms suggestive of hepatotoxicity occurred) above baseline values were found more frequently in the elderly (38 versus 18%, p < 0.05) and were also more pronounced in them (p < 0.01). The ratio of the highest transaminase value over the baseline value was called the transaminase index (TI). A TI of at least 5 was found in 22% of elderly and 8% of younger patients (p = NS), but ratios as high as 10 were mostly asymptomatic and always normalized progressively without treatment adjustment. Only symptomatic patients with a TI > or = 10 (five elderly and three younger) required temporary or definitive treatment adjustment. We conclude that repeated liver function test evaluations are generally unnecessary, except for symptomatic elderly and younger patients alike, in order to detect those with a TI > or = 10, thus requiring drug adjustment.

Diagnostic and Therapeutic Problems of Pulmonary Tuberculosis in Elderly Patients

“…However, the majority of studies show that the elderly are more susceptible to anti-TB drug induced hepatotoxicity (12, 13). Using a similar definition to that used in the present study (i.e., serum transaminase >3×the normal upper limit), Fernandez-Villar et al (30) found an 18.2% incidence of hepatotoxicity in the risk factor group (advanced age, chronic liver disease, abuse of alcohol, and others), and van den Brande et al (31) a 22% incidence of hepatotoxicity (transaminase increase >5 times the basal level) in elderly TB patients. Sharma et al (29) also reported a 16.2% drug-induced hepatotoxicity level in the elderly.…”

Hepatotoxicity of Rifampin and Pyrazinamide in the Treatment of Latent Tuberculosis Infection in HIV-Infected Persons: Is It Different Than in HIV-Uninfected Persons?

“…In a recent Canadian series of 430 persons treated for active TB with isoniazid, rifampin, pyrazinamide, and ethambutol, 3% developed clinical hepatitis [16]. Other studies, using less defined measures, have reported rates of hepatocellular damage in у5% of patients receiving treatment for TB [17,18]. Therefore, the rates of hepatotoxicity found in the trials of LTBI in HIV-positive persons are in the range reported from most treatment studies, and the rates found in HIV-negative persons receiving rifampin plus pyrazinamide for treatment of LTBI are higher than expected.…”

Pharmacokinetic and Pharmacodynamic Factors That Can Affect Sensitivity to Neurotoxic Sequelae in Elderly Individuals

“…For example, serum transaminases were used as an index of hepatotoxicity from combined isoniazid/rifampin therapy in pulmonary tuberculosis patients (Van Den Brande et al 1995). Before antituberculosis treatment, serum transaminase levels were similar in a group of 67 young patients (mean age, 38.6 years) and 64 elderly patients (mean age, 71.2 years); subjects with pre-existing hepatic disease were eliminated from the study.…”