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Tablets or oral suspension for posaconazole in lung transplant recipients? Consequences for trough concentrations of tacrolimus and everolimus
Author(s) -
Chanoine Sébastien,
GautierVeyret Elodie,
Pluchart Hélène,
Tonini Julia,
Fonrose Xavier,
Claustre Johanna,
Bedouch Pierrick,
StankeLabesque Françoise
Publication year - 2021
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.14398
Subject(s) - medicine , bioavailability , pharmacokinetics , posaconazole , calcineurin , pharmacology , transplantation , itraconazole , antifungal , dermatology
Aims A new formulation of posaconazole (PCZ), delayed‐release tablets (PCZ‐tab), increases PCZ bioavailability and plasma trough concentrations (C min ) over those achieved with an oral suspension (PCZ‐susp). PCZ is an inhibitor of cytochrome P450 3A4 and P‐glycoprotein. We therefore investigated the impact of PCZ‐tab treatment on blood C min and doses of tacrolimus (TAC) and everolimus (EVR). Methods Eighteen lung transplant patients receiving TAC ( n = 13) or TAC + EVR ( n = 5) between June 2015 and March 2016 were retrospectively included. Ten of these patients received both PCZ‐tab and PCZ‐susp (i.e. switched patients); the other 8 received only PCZ‐tab. Plasma C min of PCZ ( n = 64), blood C min of TAC ( n = 299) and EVR ( n = 80) were determined during routine therapeutic drug monitoring by liquid chromatography–tandem mass spectrometry. Results PCZ C min on PCZ‐tab treatment ( n = 48) was 2.5 times higher than that on PCZ‐susp therapy ( n = 16), for both PCZ patients ( P < .0001) and for switched patients ( P = .003). PCZ initiation, regardless of galenic form, increased TAC and EVR C min adjusted for dose (D), 3‐fold and 3.5‐fold, respectively ( P < .0001 for both). PCZ‐tab treatment was associated with a higher TAC C min /D (PCZ‐tab vs PCZ‐susp: 0.004 ± 0.004 L −1 vs 0.009 ± 0.006 L −1 , P < .0001) and lower TAC daily dose than PCZ‐susp (PCZ‐tab vs PCZ‐susp: 1.08 ± 0.92 vs 2.32 ± 1.62 mg d –1 , P < .0001). EVR C min /D was higher and EVR dose tended to be lower on PCZ‐tab than on PCZ‐susp. Conclusion The greater PCZ exposure achieved during PCZ‐tab treatment increased drug–drug interactions with TAC and EVR, resulting in greater exposure, potentially exposing patients to higher risks of adverse effects.