Antifungal prophylaxis with posaconazole in patients with acute myeloid leukemia: dose intensification coupled with avoidance of proton pump inhibitors is beneficial in shortening time to effective concentrations.
This study aimed to assess the influence of dose frequency and the presence or absence of cotreatment with proton pump inhibitors (PPIs) on the time to a target trough concentration (Cmin) of >700 ng/ml with posaconazole in the first 8 days of antifungal prophylaxis in hematological patients. This was a retrospective, observational study performed with 42 adult patients with acute myeloid leukemia who underwent posaconazole prophylaxis with 200 mg every 8 h (q8h) or 200 mg q6h after receiving induction chemotherapy and who had at least three subsequent therapeutic drug monitoring assessments during the first 8 days of treatment. The cohort was split into four groups (group 1, 200 mg q8h without PPI; group 2, 200 mg q8h with PPI; group 3, 200 mg q6h without PPI; group 4, 200 mg q6h with PPI). Rapid attainment of the target Cmin was obtained only in group 3 (P < 0.01) (median Cmin on day 4 of 935.5 ng/ml [interquartile range, 760.0 to 1,270.0 ng/ml] in group 3, versus 567.0 ng/ml [346 to 906 ng/ml] in group 1, 420.0 ng/ml [326.2 to 527.2 ng/ml] in group 2, and 514.0 ng/ml [403.7 to 564.7 ng/ml] in group 4). A linear accumulation of posaconazole over time was observed among patients in groups 1 and 3, regardless of the total daily dosage, differently from what occurred among those receiving PPI cotreatment (groups 2 and 4). Dose intensification (200 mg q6h) coupled with avoidance of PPI coadministration may represent a very powerful strategy to rapidly achieve effective concentrations with posaconazole in neutropenic hematological patients.
Institute of Clinical Pharmacology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.
Piergiorgio
P
Cojutti
Anna
A
Candoni
Erica
E
Simeone
Loretta
L
Franceschi
Renato
R
Fanin
Federico
F
Pea
D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000150:complications / Q000382:microbiology / Q000517:prevention & control*; D054328:Proton Pump Inhibitors; D012189:Retrospective Studies; D014230:Triazoles / Q000627:therapeutic use*
D000935:Antifungal Agents; D054328:Proton Pump Inhibitors; D014230:Triazoles; C101425:posaconazole