Abstract
INTRODUCTION: Rifamycins are a class of antibiotics crucial for the treatment of tuberculosis (TB). Although the development of rifamycin derivatives has revolutionized TB therapy, they are associated with hepatotoxicity, which limits their clinical use. AREAS COVERED: This review summarizes the development, clinical applications, and hepatotoxicity of rifamycin derivatives. We highlight the mechanisms of rifamycin drug-induced liver injury (DILI) and discuss strategies to improve the safety profiles of rifamycin derivatives. Relevant literature was reviewed by searching PubMed and SciFinder for articles published up to January 2025. EXPERT OPINION: The hepatotoxicity of rifamycin derivatives remains a challenge in clinical practice. Further research is needed to clarify the detailed mechanisms of rifamycin-induced liver injury. Mechanism-based strategies are also expected to prevent the toxicity of rifamycin derivatives.