Managing antituberculosis drug therapy by therapeutic drug monitoring of rifampicin and isoniazid

Abstract

Background: Current therapeutic regimens with rifampicin and isoniazid have proven successful in treating tuberculosis, however, toxicity, therapeutic failure, relapse and multiple drug resistance are serious ­concerns. Optimizing drug dose using therapeutic drug monitoring (TDM) may be a better approach than administering therapy as a standard dose. Aims: To establish and evaluate a TDM service to ­optimize rifampicin and isoniazid therapy. Methods: A TDM service for rifampicin and isoniazid was established in November 1998. Drug concentration data were collected, with relevant information to interpret the results. The reason for the request, information on concomitant drug administration and a questionnaire to assess clinical response to the drug results were also obtained. Results: Ninety patient episodes were accepted for study. The rifampicin plasma concentrations showed significant scatter, with 46% of the rifampicin concentrations below the normal range and 2% above the normal range. Similarly, 48% of isoniazid concen­trations were below the lower target of the normal range and 29% were above the upper normal limit. There was a greater proportion of isoniazid concentrations above the normal range in female patients. Conclusion: Significant pharmacokinetic variability was observed for rifampicin and isoniazid in the patient population studied. Further, a substantial number of plasma concentrations fell outside the suggested normal range for both drugs. Isoniazid plasma concentrations were significantly higher in female patients compared with male patients. Despite these abnormal results, the dose of rifampicin and isoniazid was altered in only 17% of patients, however, many patients received follow‐up education because of the drug result. The service was considered valuable by 83% of respondents to the questionnaire. While TDM of rifampicin and isoniazid is a valuable tool to optimize the dose of these drugs in some patients, there is an urgent need for concentration−effect studies and possibly education on the principles and practice of TDM for these drugs. (Intern Med J 2003; 33: 229−234)