TY - JOUR
T1 - Factors influencing posaconazole plasmatic concentrations in patients presenting with acute myeloid leukemia
AU - Desplanques, P. Y.
AU - Burlacu, R.
AU - Poinsignon, V.
AU - Boussion, H.
AU - Borget, I.
AU - Wyplosz, B.
AU - De Botton, S.
AU - Billaud, E.
AU - Chachaty, E.
AU - Gachot, B.
AU - Netzer, F.
AU - Micol, J. B.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Purpose: The effectiveness of posaconazole (PSZ) prophylaxis on invasive fungal infections, in patients presenting with acute myeloid leukemia (AML), seems to be correlated to its blood plasma concentration. Our goal was to identify the risk factors for underdosing. Patients and methods: We retrospectively reviewed the records of patients treated for AML treated with PSZ, during a 2-year period. Assays. < 500. ng/mL were considered as under dosed. Results: Fifty-nine assays (43 patients) were performed during induction (n= 22) or consolidation (n= 37) chemotherapy. PSZ treatment was initiated within a median of 3 days before neutropenia with a first assay performed at 8 days (3-28). The median PSZ blood plasma concentration was 375. ng/mL (< 200-1900). Forty-one (69%) treatment were maintained until the end of neutropenia. One patient presented with candidemia, 9 with possible invasive aspergillosis, without any significant association with underdosing. The univariate analysis showed that co-administration of proton pump inhibitors (PPIs) (P= 0.01) and cause of hospitalization (induction chemotherapy vs consolidation, P= 0.008) were associated with underdosing, contrary to feeding difficulties (P= 0.07) and digestive disorders (P= 0.5). The multivariate analysis confirmed the impact of PPI use (P= 0.01) and the cause of hospitalization (P= 0.003). Conclusion: This study highlights the major impact of PPI administration on PSZ blood plasma levels and stresses the risk of non-effective prophylaxis during induction treatment of AML.
AB - Purpose: The effectiveness of posaconazole (PSZ) prophylaxis on invasive fungal infections, in patients presenting with acute myeloid leukemia (AML), seems to be correlated to its blood plasma concentration. Our goal was to identify the risk factors for underdosing. Patients and methods: We retrospectively reviewed the records of patients treated for AML treated with PSZ, during a 2-year period. Assays. < 500. ng/mL were considered as under dosed. Results: Fifty-nine assays (43 patients) were performed during induction (n= 22) or consolidation (n= 37) chemotherapy. PSZ treatment was initiated within a median of 3 days before neutropenia with a first assay performed at 8 days (3-28). The median PSZ blood plasma concentration was 375. ng/mL (< 200-1900). Forty-one (69%) treatment were maintained until the end of neutropenia. One patient presented with candidemia, 9 with possible invasive aspergillosis, without any significant association with underdosing. The univariate analysis showed that co-administration of proton pump inhibitors (PPIs) (P= 0.01) and cause of hospitalization (induction chemotherapy vs consolidation, P= 0.008) were associated with underdosing, contrary to feeding difficulties (P= 0.07) and digestive disorders (P= 0.5). The multivariate analysis confirmed the impact of PPI use (P= 0.01) and the cause of hospitalization (P= 0.003). Conclusion: This study highlights the major impact of PPI administration on PSZ blood plasma levels and stresses the risk of non-effective prophylaxis during induction treatment of AML.
KW - Acute myeloid leukemia
KW - Drug interactions
KW - Invasive aspergillosis
KW - Posaconazole
UR - http://www.scopus.com/inward/record.url?scp=84899900803&partnerID=8YFLogxK
U2 - 10.1016/j.medmal.2014.02.005
DO - 10.1016/j.medmal.2014.02.005
M3 - Article
C2 - 24656841
AN - SCOPUS:84899900803
SN - 0399-077X
VL - 44
SP - 174
EP - 179
JO - Medecine et Maladies Infectieuses
JF - Medecine et Maladies Infectieuses
IS - 4
ER -