rifabutin + itraconazole

Rifabutin + itraconazole is a combination of two pharmaceutical agents: rifabutin, an antibiotic from the rifamycin class primarily used for Mycobacterium avium complex (MAC) and tuberculosis, and itraconazole, a triazole antifungal mainly indicated for systemic fungal infections (such as chronic pulmonary aspergillosis and histoplasmosis). Rifabutin inhibits bacterial DNA-dependent RNA polymerase, while itraconazole inhibits fungal 14-alpha demethylase, a key enzyme for ergosterol biosynthesis, thus disrupting fungal cell membrane formation. When administered together, rifabutin—an inducer of CYP3A—significantly decreases serum concentrations of itraconazole by enhancing its metabolism, risking subtherapeutic itraconazole exposure and treatment failure. This combination is not recommended unless absolutely necessary; such use demands close therapeutic drug monitoring due to both decreased efficacy of itraconazole and possible increased rifabutin toxicity, including uveitis[1][3].