posaconazole + benznidazole

Posaconazole + benznidazole is an oral fixed-dose combination of two small-molecule antiparasitic drugs, evaluated primarily for the treatment of Chagas disease (American trypanosomiasis) caused by *Trypanosoma cruzi*. Posaconazole is a triazole antifungal that inhibits the parasite's sterol 14α-demethylase (CYP51), interfering with ergosterol biosynthesis in *T. cruzi*. Benznidazole is a nitroimidazole that causes DNA damage and has trypanocidal activity via production of free radicals and nitroreduction. In preclinical murine models, the combination demonstrated synergistic anti-*T. cruzi* activity, enhancing cure rates and allowing lower doses to be used synergistically, potentially reducing toxicity and risk of resistance[1][2]. In clinical studies, this combination did not outperform benznidazole monotherapy for sustained parasite clearance but showed improved initial trypanocidal action and tolerability compared to benznidazole alone[3].