Tablets Or Oral Suspension For Posaconazole In Lung Transplant Recipients? Consequences For Trough Concentrations Of Tacrolimus And Everolimus

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-tabvsPCZ-susp: 0.004 +/- 0.004 L(-1)vs0.009 +/- 0.006 L-1,P <.0001) and lower TAC daily dose than PCZ-susp (PCZ-tabvsPCZ-susp: 1.08 +/- 0.92vs2.32 +/- 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.