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Clinical relevance of rifampicin-moxifloxacin interaction in isoniazid resistant/intolerant tuberculosis patients
Clinical relevance of rifampicin-moxifloxacin interaction in isoniazid resistant/intolerant tuberculosis patients
- Source :
- Antimicrobial Agents and Chemotherapy, 66(2):e01829-21. AMER SOC MICROBIOLOGY, Antimicrob Agents Chemother
- Publication Year :
- 2022
-
Abstract
- Moxifloxacin is an attractive drug for the treatment of isoniazid-resistant rifampicin-susceptible tuberculosis (TB) or drug-susceptible TB complicated by isoniazid intolerance. However, co-administration with rifampicin decreases moxifloxacin exposure. It remains unclear whether this drug-drug interaction has clinical implications. This retrospective study in a Dutch TB centre investigated how rifampicin affected moxifloxacin exposure in patients with isoniazid-resistant or -intolerant TB. Moxifloxacin exposures were measured between 2015 and 2020 in 31 patients with isoniazid-resistant or -intolerant TB receiving rifampicin, and 20 TB patients receiving moxifloxacin without rifampicin. Moxifloxacin exposure, i.e. area under the concentration-time curve (AUC0-24h), and attainment of AUC0-24h/minimal inhibitory concentration (MIC) > 100 were investigated for 400 mg moxifloxacin and 600 mg rifampicin, and increased doses of moxifloxacin (600 mg) or rifampicin (900 mg). Moxifloxacin AUC0-24h and peak concentration with a 400 mg dose were decreased when rifampicin was co-administered compared to moxifloxacin alone (ratio of geometric means 0.61 (90% CI (0.53, 0.70) and 0.81 (90% CI (0.70, 0.94), respectively). Among patients receiving rifampicin, 65% attained an AUC0-24h/MIC > 100 for moxifloxacin compared to 78% of patients receiving moxifloxacin alone; this difference was not significant. Seven out of eight patients receiving an increased dose of 600 mg moxifloxacin reached the target AUC0-24h/MIC > 100. This study showed a clinically significant 39% decrease in moxifloxacin exposure when rifampicin was co-administered. Moxifloxacin dose adjustment may compensate for this drug-drug interaction. Further exploring the impact of higher doses of these drugs in patients with isoniazid resistance or intolerance is paramount.
- Subjects :
- Drug
medicine.medical_specialty
Tuberculosis
media_common.quotation_subject
Moxifloxacin
Antitubercular Agents
Clinical Therapeutics
Gastroenterology
Minimum inhibitory concentration
Internal medicine
Tuberculosis, Multidrug-Resistant
medicine
Isoniazid
Humans
Pharmacology (medical)
Clinical significance
heterocyclic compounds
media_common
Retrospective Studies
Pharmacology
business.industry
Retrospective cohort study
biochemical phenomena, metabolism, and nutrition
medicine.disease
bacterial infections and mycoses
Infectious Diseases
Rifampin
business
Rifampicin
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 10986596
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy, 66(2):e01829-21. AMER SOC MICROBIOLOGY, Antimicrob Agents Chemother
- Accession number :
- edsair.doi.dedup.....15a9f9ff8a8cc9d29e04b52704049c4b