TY - JOUR
T1 - High-dose rifampicin in tuberculosis: Experiences from a Dutch tuberculosis centre
AU - Seijger, Charlotte
AU - Hoefsloot, Wouter
AU - Guchteneire, Inge Bergsma-De
AU - te Brake, Lindsey
AU - van Ingen, Jakko
AU - Kuipers, Saskia
AU - van Crevel, Reinout
AU - Aarnoutse, Rob
AU - Boeree, Martin
AU - Magis-Escurra, Cecile
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Background Recent evidence suggests that higher rifampicin doses may improve tuberculosis (TB) treatment outcome. Methods In this observational cohort study we evaluated all TB patients who were treated with high-dose rifampicin (> 10 mg/kg daily) in our reference centre, from January 2008 to May 2018. Indications, achieved plasma rifampicin exposures, safety and tolerability were evaluated. Results Eighty-eight patients were included. The main indications were low plasma concentrations (64.7%) and severe illness (29.5%), including central nervous system TB. Adjusted rifampicin 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 rifampicin immediately, the others had a higher dosage guided by therapeutic drug monitoring. Four patients developed hepatotoxicity, of which two were proven due to isoniazid. Re-introduction of high-dose rifampicin was successful in all four. Eighty-seven patients tolerated high-dose rifampicin well throughout treatment. Only one patient required a dose reduction due to gastro-intestinal disturbance. Conclusion High-dose rifampicin, 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 rifampicin dosage if a reduced medication absorption or a poor treatment outcome is suspected. We suggest to administer high-dose rifampicin to patients with severe manifestations of TB or low rifampicin exposure to improve treatment outcome.
AB - Background Recent evidence suggests that higher rifampicin doses may improve tuberculosis (TB) treatment outcome. Methods In this observational cohort study we evaluated all TB patients who were treated with high-dose rifampicin (> 10 mg/kg daily) in our reference centre, from January 2008 to May 2018. Indications, achieved plasma rifampicin exposures, safety and tolerability were evaluated. Results Eighty-eight patients were included. The main indications were low plasma concentrations (64.7%) and severe illness (29.5%), including central nervous system TB. Adjusted rifampicin 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 rifampicin immediately, the others had a higher dosage guided by therapeutic drug monitoring. Four patients developed hepatotoxicity, of which two were proven due to isoniazid. Re-introduction of high-dose rifampicin was successful in all four. Eighty-seven patients tolerated high-dose rifampicin well throughout treatment. Only one patient required a dose reduction due to gastro-intestinal disturbance. Conclusion High-dose rifampicin, 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 rifampicin dosage if a reduced medication absorption or a poor treatment outcome is suspected. We suggest to administer high-dose rifampicin to patients with severe manifestations of TB or low rifampicin exposure to improve treatment outcome.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062940410&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30870476
U2 - 10.1371/journal.pone.0213718
DO - 10.1371/journal.pone.0213718
M3 - Article
C2 - 30870476
VL - 14
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 3
M1 - e0213718
ER -