New Tuberculosis Treatment, Old Problems: 100% Adverse Reactions in Thai Tuberculosis Patients on the Rifapentine-Moxifloxacin Regimen

Abstract Introduction: The 4-month rifapentine-moxifloxacin (HPMZ) regimen has recently been shown to be as effective as the standard 6-month rifampicin-based regimen for drug-susceptible pulmonary tuberculosis. Clinical trials reported serious adverse drug reactions (ADRs) in only 18% of patients, with a low incidence of grade 3 hyperbilirubinemia (3.3%) in the HPMZ group. However, real-world practice at our institute in Thailand has suggested otherwise. Case description: We report a case series of four patients with pulmonary tuberculosis treated with the HPMZ regimen at the Central Chest Institute of Thailand in 2023. All four patients developed serious ADRs within the first 21 days of starting the regimen: Case 1: A 58-year-old woman started on HPMZ. After 12 days, she reported mild fatigue and nausea, with liver tests showing total bilirubin (TBIL)/direct bilirubin (DBIL) of 4.2/3.04 mg/dL, indicating grade 3 cholestasis from rifapentine. Case 2: A 65-year-old man started on HPMZ. After 15 days, while being asymptomatic, liver tests showed TBIL/DBIL levels of 4.3/3.19 mg/dL. He was diagnosed with grade 3 cholestasis due to rifapentine. Case 3: A 72-year-old male with COPD and paroxysmal atrial fibrillation started on HPMZ. His TBIL/DBIL were initially 1.1/0.45 but rose to 3.7/2.57 mg/dL after 21 days indicating grade 3 cholestasis attributed to rifapentine. He also experienced severe myalgia, arthralgia, and hypoglycemia from Moxifloxacin. Case 4: 73-year-old male started on HPMZ. After 7 days, he experienced fatigue, myalgia, rash, and fever. He was diagnosed with an allergic rash from pyrazinamide and severe flu-like syndrome from rifapentine. All patients discontinued the HPMZ regimen, resulting in symptom resolution and normalization of liver function tests. Conclusion: This case series reveals a significant discrepancy between clinical trial data and real-world experience with the HPMZ regimen in Thailand. The 100% incidence of serious ADRs, including three cases of grade 3 cholestasis and one severe flu-like syndrome, contrasts sharply with lower trial rates. These findings suggest a potential population-specific susceptibility, highlighting the need for close monitoring and re-evaluation of HPMZ use. Further research is necessary to understand the mechanisms and risk factors for these adverse reactions.