Deriving Dosages for Levofloxacin Tuberculosis Preventive Treatment for Young People Exposed to Rifampicin-Resistant Tuberculosis.
Academic Article
Overview
abstract
BACKGROUND: Tuberculosis (TB) is the leading single bacterial cause of death worldwide. In 2023, approximately 400 000 people developed multidrug- and rifampicin-resistant TB (MDR/RR-TB), which complicates treatment. TB preventive treatment (TPT) is a critical strategy to prevent the progression from TB infection to TB disease among those at risk. In February 2024, based on data from 2 randomized controlled trials, levofloxacin was strongly recommended by the World Health Organization (WHO) as a TPT option in people of all ages exposed to MDR/RR-TB. There are uncertainties about the optimal dosing of levofloxacin in children and adolescents when using dispersible and solid formulations. We used pharmacokinetic modeling and simulations to determine the best dosing strategy in people aged up to 19 years for both formulations of levofloxacin. METHODS: A previously developed population pharmacokinetic model of levofloxacin in children (0.2-16.8 years) was used and applied to new WHO harmonized weight bands. Simulations were conducted using demographic data from countries with the highest incidence of RR- or MDR-TB. Two currently available levofloxacin formulations (100 mg pediatric, dispersible tablets and 250 mg solid tablets) were considered. RESULTS: A dosing regimen by weight band was developed for levofloxacin when used as TPT in people aged 0-19 years exposed to MDR/RR-TB. Doses correspond to 8-33 mg/kg for the 100 mg dispersible tablets and 10-42 mg/kg for 250 mg solid tablets. These doses achieve adequate adult target exposure levels. CONCLUSIONS: Pragmatic, weight-band dosing strategies help simplify the administration of MDR/RR-TB TPT and have been included in WHO guidance.
