Comparison of posaconazole serum concentrations from haematological cancer patients on posaconazole tablet and oral suspension for treatment and prevention of invasive fungal infections

Abstract

Posaconazole tablet formulation (PTF) was developed to optimise bioavailability. This study compared posaconazole levels between patients on the PTF and oral suspension formulation (OSF). We also examined factors that may impact posaconazole levels. The primary and secondary objectives were analysed by comparing trough levels and attainment of target level between the formulation groups. For the 86 patients on PTF and 176 on OSF, the mean first levels was 1.32 μg ml (SD = 0.69) and 0.81 μg ml (SD = 0.59), P < 0.0001 respectively. PTF group was more likely to achieve levels ≥0.7 μg ml than OSF group (OR 7.97 [95 CI; 3.75-16.93], P < 0.0001). Levels from patients on PTF and with presence of acid suppression, GI GVHD, mucositis or diarrhoea were not statistically different from those without these factors. For PTF, no correlation was found between patient's weight (kg) and levels (R = 0.0536, P = 0.035). The incidences of elevation in ALT/AST or Tbili were similar between the formulation groups. In conclusion, PTF should be considered the preferred formulation because it demonstrated better absorption than the OSF. Patients on PTF for prophylaxis are more likely to attain target level and may not routinely require therapeutic drug monitoring during prophylaxis.

Real-Life Assessment of the Safety and Effectiveness of the New Tablet and Intravenous Formulations of Posaconazole in the Prophylaxis of Invasive Fungal Infections via Analysis of 343 Courses

“…The tablet and intravenous formulations were approved on the basis of safety and pharmacokinetic data, with corresponding phase III data for the tablet formulation recently being published (9). To date, several small, single-center studies have reviewed the initial implementation of PCZ tablets, focusing mainly on pharmacokinetic endpoints (5,6,(10)(11)(12). In agreement with our early experience, those reports also have shown that PCZ tablets yield higher serum concentrations than the suspension formulation and appear to be safe (5).…”

“…The recently available intravenous (i.v.) and delayed-release (DR) tablet formulations of PCZ result in significantly higher serum PCZ concentrations and increased attainment of traditional pharmacokinetic targets, compared to the PCZ suspension (5,6). Additionally, the DR formulation has been demonstrated to provide more consistent absorption and is minimally affected by gastric pH and motility (7,8).…”

New facets of antifungal therapy

“…39,40 The delayed release oral tablet is considered a more reliable option for the prophylaxis or treatment of IFIs. Studies have suggested that the posaconazole oral tablet has higher azole plasma levels 41 , better absorption 42 , and improved bioavailability 43 than that of oral suspension. Furthermore, an intravenous formulation of posaconazole was developed and FDA-approved in 2014 for patients who are unable to take oral medications.…”

In Vivo 11β-Hydroxysteroid Dehydrogenase Inhibition in Posaconazole-Induced Hypertension and Hypokalemia

“…Frequently used for the prevention of fungal infections in high-risk populations, this agent is also useful during the treatment of multiple forms of aspergillosis (1). Recent studies have shown that the new posaconazole delayed-release tablets have superior bioavailability compared to the liquid suspension formulation (2,3). As higher serum posaconazole concentrations have been associated with improved clinical responses (4), this formulation has been a welcome addition to available treatment options.…”