Therapeutic drug monitoring of isoniazid and rifampicin during anti-tuberculosis treatment in Auckland, New Zealand

Abstract

Setting: There is uncertainty as to the optimal therapeutic concentrations of anti-tuberculosis drugs to achieve cure.

Objective: To characterise the use of therapeutic drug monitoring (TDM), and identify risk factors and outcomes for those with concentrations below the drug interval.

Design: Patients treated for tuberculosis (TB) who had rifampicin (RMP) or isoniazid (INH) concentrations measured between 1 January 2005 and 31 December 2012 were studied retrospectively. Matched concentrations and drug dosing time were assessed according to contemporary regional drug intervals (RMP > 6 μmol/l, INH > 7.5 μmol/l) and current international recommendations (RMP > 10 μmol/l, INH > 22 μmol/l). Outcomes were assessed using World Health Organization criteria.

Results: Of 865 patients, 121 had concentrations of either or both medications. RMP concentrations were within the regional drug intervals in 106/114 (93%) and INH in 91/100 (91%). Concentrations were within international drug intervals for RMP in 76/114 (67%) and INH in 53/100 (53%). Low weight-based dose was the only statistically significant risk factor for concentrations below the drug interval. Of the 35 patients with low concentrations, 21 were cured, 9 completed treatment and 5 transferred out. There were no relapses during follow-up (mean 66.5 months).

Conclusion: There were no clinically useful characteristics to guide use of TDM. Many patients had concentrations below international therapeutic intervals, but were successfully treated.