Antifungal prophylaxis with posaconazole in patients with acute myeloid leukaemia: dose intensification coupled with avoidance of proton pump inhibitors is beneficial in shortening time to effective concentrations.

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Antifungal prophylaxis with posaconazole in patients with acute myeloid leukaemia: dose intensification coupled with avoidance of proton pump inhibitors is beneficial in shortening time to effective concentrations.

Antimicrob Agents Chemother. 2013 Sep 23;

Authors: Cojutti P, Candoni A, Simeone E, Franceschi L, Fanin R, Pea F

Abstract
This study aimed to assess the influence of dose frequency and presence or absence of cotreatment with proton pump inhibitors (PPIs) on time to target trough level of > 700 ng/mL (Cmin) with posaconazole in the first 8 days of antifungal prophylaxis in haematological patients. This was a retrospective, observational study performed in 42 adult patients with acute myeloid leukaemia who underwent posaconazole prophylaxis with 200 mg q8h or 200 mg q6h after receiving induction chemotherapy and who had at least three subsequent therapeutic drug monitoring 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 target Cmin was obtained only in group 3 (P<0.01) [median (IQ range) Cmin on day 4: 935.5 ng/mL (760.0-1270.0) in group 3 vs 567.0 ng/mL (346-906) in group 1 vs 420.0 ng/mL (326.2-527.2) in group 2 and 514.0 ng/mL (403.7-564.7) 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 PPIs coadministration may represent a very powerful strategy to rapidly achieve effective concentrations with posaconazole in neutropenic haematological patients.

PMID: 24060872 [PubMed - as supplied by publisher]