P142 Rifampicin therapeutic drug monitoring – an individualised dosing approach in tuberculosis

<h3>Introduction</h3> Rifampicin plays a key role in tuberculosis (TB) treatment, due to its bactericidal and sterilizing capacity. The dose currently recommended by WHO is 10 mg/kg but achieving this dose can be limited by fixed dose preparations and risks under dosing. Low plasma levels of rifampicin may potentially contribute to poor treatment response. Therapeutic drug monitoring (TDM) has been proposed as a method to support early optimisation of dosing particularly in high-risk groups e.g. CNS TB or slow treatment response. The main aim of this study was to investigate whether standard dosing of rifampicin is likely to lead to therapeutic drug levels and to describe the impact of dose escalation. <h3>Method</h3> We performed a retrospective review of all adult patients who had rifampicin levels (2 hours post dose or 6 hours where delayed absorption was suspected) taken between August 2018 and August 2021, identifying 58 patients. Patient demographics, clinical characteristics including weight at time of level, dose adjustments and rationale for taking level were collected from patient records. Levels below 8 mg/L were considered subtherapeutic. <h3>Results</h3> The most frequent reason for conducting a rifampicin level was due to slow/poor response (34%) followed by high burden of disease (24%). Just under half of patients (48%) were being treated for pulmonary TB, followed by extrapulmonary TB (24%). Of the 58 patients who had levels measured, 40 (69%) patients had levels that were considered to be subtherapeutic. Figure 1 displays if therapeutic levels were achieved with standard rifampicin dosing (10 mg/kg). In the subtherapeutic group, 31 (78%) had their dosage increased of which 19 (61%) patients had a level taken post dose escalation. Eleven 11 (58%) patients from this group had levels within therapeutic range. <h3>Conclusion</h3> Based on our finding’s a significant proportion of patients show subtherapeutic levels on standard dosing particularly in those with apparent severe or poorly responding disease. TDM is a useful tool to individualise rifampicin dosing and early optimisation increases the likelihood of attaining a therapeutic level. This may be particularly beneficial in patients who may be at risk of low plasma levels e.g. malnourished/disseminated/CNS TB.