Real-world challenges of 4-month rifapentine-moxifloxacin TB regimen: High hyperbilirubinemia in Thailand.

BACKGROUND

The four-month rifapentine-moxifloxacin (HPMZ) regimen is an alternative to the standard six-month tuberculosis treatment. While clinical trials confirm its efficacy, real-world data, especially in Asian populations, are limited. This study evaluates the effectiveness and tolerability of HPMZ in Thailand.

METHODS

A prospective study was conducted at the Central Chest Institute of Thailand (September 2023-June 2025) in drug-susceptible TB patients. The HPMZ regimen included daily rifapentine 1200 mg, moxifloxacin 400 mg, isoniazid 300 mg, and weight-based pyrazinamide for eight weeks, followed by rifapentine, moxifloxacin, and isoniazid for nine weeks. Patients were monitored for adverse events (AEs).

RESULTS

Fourteen participants (median age 54 years, weight 55.35 kg) received a mean rifapentine dose of 21.26 mg/kg. Hyperbilirubinemia was the most common AEs, leading to treatment discontinuation in 78.57%. Grade 3 hyperbilirubinemia occurred in 57.14%, with a mean peak bilirubin level of 3.03 mg/dL. Rifapentine overexposure was observed, with five patients showing a mean maximum plasma concentration (Cmax) of 41.89 ± 10.42 μg/mL.

CONCLUSION

The high incidence of hyperbilirubinemia suggests a fixed 1200 mg rifapentine dose may not be suitable for lower-weight populations. Weight-based rifapentine dosing and standardized ADR management are crucial for broader implementation. Larger studies are needed to refine dosing and evaluate effectiveness and tolerability.