The tablet formulation of posaconazole: clinical pharmacology and the use in patients with hematologic malignancies

Abstract

Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various fungi, including yeast and molds, including Mucorales, what makes a key difference with itraconazole and voriconazole. Clinical studies have demonstrated his efficacy for prophylaxis against invasive fungal infections in hematological patients at high risk (with acute myeloid leukemia, myelodysplastic syndrome, aplastic anemia, and in patients after hematopoietic stem cell transplantation, especially with graft versus host disease). Posaconazole also use as salvage therapy against invasive aspergillosis, mucormycosis and some other systemic mycoses. For today there are 3 posaconazole formulations – oral suspension, modify release tablet and intravenous solution (not registered in Russia at the time of writing this paper). As far as bioavailability of posaconazole following administration by oral suspension is highly variable with low unstable plasma concentrations and there are number of factors with negatively influence to the pharmacokinetic profile of suspension a delayed-release tablet was developed using hot-melt extrusion technology with a pH-sensitive polymer. The tablet formulation releases the drug in the intestine, and this leads to the enhanced bioavailability and increased posaconazole exposure parameters and, as a result, to a higher efficacy. This was demonstrated in pre-clinical, early phase clinical studies and confirmed with data from real practice. The tablet formulation has well tolerability profile with a low incidence of clinically significant adverse events. For today posaconazole included in all relevant clinical recommendations with high levels of evidence, including prophylaxis of invasive mycoses and therapy of their refractory forms, while the authors agree that for the oral therapy a preference should be given to the tablet formulation of posaconazole.