Safety study and therapeutic drug monitoring of the oral tablet formulation of posaconazole in patients with haematological malignancies

Abstract

Posaconazole was well tolerated; however, LFT abnormalities were frequent. ADR occurrence was not linked to posaconazole exposure. Because posaconazole concentrations were highly variable, TDM can be helpful to avoid underexposure to the drug and increase its efficacy in preventing IFI. Conversely, a large proportion of patients was overexposed and might have benefited of a dose reduction.

Co‐administration of proton pump inhibitors and/or of steroids may be a risk factor for low trough concentrations of posaconazole delayed‐released tablets in adult patients with haematological malignancies

“…We observed a median C min 1.17 mg l −1 , with a range of 0.17–4.53 mg l −1 and an overall CV of 50.4%. The extent of inter‐ and intra‐patient variability were 43.9% and 29.3%, respectively, similarly to those previously reported . Furthermore, the proportion of subtherapeutic C min is comparable (17.0% in our study vs .…”

“…Marked variability in posaconazole exposure is still observed in PK studies of the delayed‐released tablet formulation . Patients receiving 300 mg daily have a median posaconazole C min concentration of 1.08–1.89 mg l −1 at steady state with a concentration range of <0.1–7.89 mg l −1 .…”

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

“…In the phase 3 study of the delayed-release tablet POS, C min from 0.5 to 3.75 mg/L was considered to be safe [1]. Moreover, recent studies failed to demonstrate any link between the POS C min and toxicity [12,14,30], even if some authors reported some cases of adverse events in patients with a POS C min > 1.8 mg/L [9,31,32]. Finally, although our results suggest that a gain of antifungal activity can be expected until a POS C min of 4.8 mg/L, additional research is needed to determine whether such POS exposure significantly improves efficacy without inducing toxicity.…”

“…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].…”

Acute kidney injury: an unusual complication of posaconazole use

“…5,11 The oral bioavailability of delayed-release posaconazole tablets is more predictable than that of the liquid suspension and higher plasma levels are achieved with the tablets when compared to the liquid suspension. 12 , It is recommended that serum levels are monitored as some patients may not achieve the desired target.…”