Posaconazole liquid vs tablet formulation in lung transplant recipients

Abstract

Posaconazole is an extended-spectrum triazole antifungal used in the treatment and prophylaxis of Aspergillus infections. It is available as oral suspension (POS-Liq) and delayed-release tablets (POS-Tab). The aim of this longitudinal, retrospective study was to compare the clinical effectiveness, toxicity and pharmacokinetics of POS-Liq vs POS-Tab in lung transplant recipients (LTx-recipients), who were treated with both formulations subsequently. Twenty-four consecutive LTx-recipients with 191 documented posaconazole trough levels (PTLs) for POS-Liq or POS-Tab were included. The administered daily doses were 300 mg for POS-Tab and 600 mg (prophylaxis) or 800 mg (therapy) for POS-Liq. Target PTLs were ≥700 ng/mL (prophylaxis) and ≥1250 ng/mL (therapy). The overall prophylactic and therapeutic response rates were 78% and 67%, respectively. No cases of hepatotoxicity or QT-prolongation were observed with either formulation. The achieved target PTLs were tripled under POS-Tab compared to POS-Liq with fewer risk factors for sub-therapeutic PTLs. Concomitant administration of POS-Tab significantly reduced the tacrolimus concentration-to-dose ratio (P = .001). We suggest the use of POS-Tab is appropriate for prophylaxis and therapy of Aspergillus infections in LTx-recipients, since POS-Tab displayed more reliable PTLs with no added adverse events. However, we recommend regular drug monitoring for POS-Liq and for therapy with POS-Tab and that immunosuppressant levels are monitored closely when the posaconazole formulation is switched.

Treatment by Posaconazole Tablets, Compared to Posaconazole Suspension, Does Not Reduce Variability of Posaconazole Trough Concentrations

“…2 and 3), the difference was small and neither clinically relevant nor statistically significantly different, suggesting that the variability of POS-tab C min is still as large as that of POS-susp C min (20). Aside from one study, which reported lower POS C min variability with the tablet regimen in 24 lung-transplant patients (8), such a comparison of the intra-and interpatient variability of POS C min between the two oral galenic formulations of POS has never been performed. Several studies reported CVs for the POS-tab C min , but comparing CV values is problematic since calculation methods of CV differ.…”

“…However, although the variability of the POS-susp trough concentrations (C min ) is known to be significant, with interindividual and within-subject coefficients of variation (CV) as high as 64% and 49%, respectively (7), little is known about the variability of the POS-tab C min . A recent crossover study showed lower within-subject CV for the POS-tab C min in lung-transplant patients treated with POS-susp and then with POS-tab (8). However, the number of patients was quite low (n ϭ 24), and interindividual CVs were not studied.…”

Why do lung transplant patients discontinue triazole prophylaxis?

“…Prior studies have demonstrated the tolerability and effectiveness of short-term PS prophylaxis. 12,13 Our data showed that patients on PS had fewer disruptions or changes in AF prophylaxis. Medication sustainability is important with AF prophylaxis as medication alterations require dose adjustments in anti-rejection medications requiring close monitoring.…”

“…Since PS is not a first‐line AF prophylactic agent at our institution, fewer patients were exposed to PS than IT or VR. Prior studies have demonstrated the tolerability and effectiveness of short‐term PS prophylaxis . Our data showed that patients on PS had fewer disruptions or changes in AF prophylaxis.…”

Refining the therapeutic range of posaconazole and isavuconazole for efficient therapeutic drug monitoring using a bioassay approach

“…The new tablet formulation makes it possible to reach higher POS C min values than for the oral suspension [6][7][8]. This greater POS C min could theoretically result in a greater risk of side effects, although no study has yet clearly highlighted increased toxicity with the POS tablet formulation [2,[9][10][11][12][13][14]. Hence, no upper threshold for the POS C min has yet been proposed, even if some authors have suggested that dose reduction could be feasible for at least half of patients [15,16].…”