Therapeutic drug monitoring (TDM) of posaconazole (SZP) in cystic fibrosis (CF) lung transplant (LTx) patients

Mr. Berge, R. Guillemain, S. Lefeuvre, P. Chevalier, V. Boussaud, C. Amrein, E. Dannaoui, E. Billaud

Abstract: 

Invasive aspergillosis Represents a major complication of LTx PARTICULARLY in case of cystic fibrosis. PSZ is Indicated for the curative and prophylactic treatment of fungal infections using respectivement 400mgx2 / day and 200mgx3 / day doses. SZP absorption is saturable, The Therefore dose Increase Often needed in CF patients is limited. SZP half life is long, resulting and in long duration to steady state (SS).

Objective: To show That SZP TDM in CFLTx allows 1- to accomplish achieve trough concentrations (C0) levels consistent with efficiency (> 0.5 mg / L) or at least detectable (> 0.2 mg / L); 2 -to manage the metabolic drug interactions with immunosuppressants.

Methods: Retrospective and prospective cohort of CFLTx under SZP entre 2006 and 2008 in our center.Longitudinal collection of Both doses and C0 (at SS) data for SZP and immunosuppressants. CT by determination of plasma SZP by LC assay with fluorimetric detection.

Results: CFLTx (n = 17) aged 26 ± 8 years received healing (n = 2), preemptive (n = 14) or prophylactic (n = 1) SZP treatment in combination with caspofungin in 8 patients. The mean treatment duration Was 228 ± 197 days, [14-621]. The post Tx period corresponded to immediate (n = 4), first year (n = 5) or beyond (n = 8). 220 SZP C0 Were Analyzed. No post Tx time exposure effect is SZP Was Observed. The mean SZP C0 Was 0.7 ± 0.5 mg / L [0.2; 1.6] using an average SZP dose of 1084 ± 310 mg / day, [733; 1889], resulting and in more than 35% of the recommended dose (p <0001 ). In 65% of patients, a dose adjustment required Was on day 11 as an average.Such adjustment has-been successful in 86% of cases. SZP Was Withdrawn (n = 8) 7 Because of negative cultures and 1 intravenous route (voriconazole + caspofungin). No particular adverse events (gastrointestinal disorders, headache) has-beens Recorded During SZP races. The immunosuppressant tacrolimus dose Was tapered by a factor 3 DURING THE coprescription with SZP.

Conclusion: SZP CT Was Useful to accomplish achieve therapeutic SZP C0 in CFLTx. DESPITE Increase and split dose, no C0> 3mg / L has-been Observed. SZP safety profile was good. Indeed, as a CYP3A4 metabolic inhibitor, joined TDM of Both SZP and immunosuppressants Appeared to be Necessary to manage the immunosuppressants dose adjustment at the introduction or discontinuation of SZP.

2008

Full conference title: 

Réunion Interdisciplinaire de Chimiothérapie Anti Infectieuse
    • RICAI 28th (2008)