High-dose rifampicin in tuberculosis: experiences from a Dutch tuberculosis centre

Background: Recent evidence suggests that higher rifampicin (R) doses may improve tuberculosis (TB) treatment outcome. Methods: In this observational cohort study we evaluated all TB patients who were treated with high-dose R (> 10 mg/kg daily) in our reference centre, from 2008- 2018. Indications, achieved plasma R exposures, safety and tolerability were evaluated. Results: 88 patients were included. The main indications were low plasma concentrations (64.7%) and severe illness (29.5%), including central nervous system TB. Adjusted R dosages ranged from 900 mg to a maximum of 2400 mg (corresponding to 32 mg/kg) per day. Patients with severe illness received high-dose R immediately, the others had a higher dosage guided by therapeutic drug monitoring. 4 patients developed hepatotoxicity, of which two were proven due to isoniazid. Re-introduction of high-dose R was successful in all four. 87 patients tolerated high-dose R well throughout treatment. Only 1 patient required a dose reduction due to gastro-intestinal disturbance. Conclusion: High-dose R, used in specific groups of patients in our clinical setting, is safe and well-tolerated for the whole treatment duration. Measurement of drug exposures could be used as a tool/guide to increase R dosage if a reduced medication absorption or a poor treatment outcome is suspected. Pending the results from clinical trials, we suggest to administer high-dose R to patients with severe manifestations of TB or low R exposure to improve treatment outcome.