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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
Author(s) -
Cojutti Pier Giorgio,
Candoni Anna,
Lazzarotto Davide,
Rabassi Nicholas,
Fanin Renato,
Hope William,
Pea Federico
Publication year - 2018
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13707
Subject(s) - posaconazole , medicine , therapeutic drug monitoring , hematopoietic stem cell transplantation , population , refractory (planetary science) , gastroenterology , transplantation , pharmacokinetics , surgery , pharmacology , antifungal , biology , dermatology , itraconazole , environmental health , astrobiology
Aims The aim of this study was to determine clinical variables associated with posaconazole exposure among adult patients with haematological malignancies who received posaconazole tablets for prophylaxis of invasive fungal infections (IFIs). Methods The study population included adult patients with haematological malignancies who received posaconazole delayed‐release tablets for prophylaxis of IFIs after induction chemotherapy for acute leukaemia or graft‐versus‐host‐disease (GVHD) complicating hematopoietic stem cell transplantation (HSCT) in the period January 2016–December 2017. Results Sixty‐six consecutive patients with 176 posaconazole C min were included for evaluation in the study. Subtherapeutic posaconazole concentrations (< 0.7 mg l −1 ) were observed at least once in 33.3% of patients (22/66), and overall in 17.0% of therapeutic drug monitoring (TDM) episodes (30/176). At multilevel linear regression, use of PPIs ( P = 0.008), use of intermediate or high dose steroids (>0.7 mg kg −1 daily) ( P = 0.022) and male gender ( P = 0.025) were significantly associated with decreased C min , whereas time from starting therapy ( P = 0.032) was associated with increased C min in our patient population. Conclusion Posaconazole exposure during treatment with delayed‐released tablet formulation may be affected by the use of PPIs and/or of intermediate or high dose steroids.