PHARMACY DRIVEN POSACONAZOLE THERAPEUTIC MONITORING IN A LEUKEMIA AND BONE MARROW TRANSPLANT CENTER

Posaconazole (POS) is an extended-spectrum triazole with proven efficacy for antifungal prophylaxis in patients (pts) undergoing HSCT or treatment of acute leukemia. The FDA recommends a goal POS average serum drug concentration of >700 ng/ml. We implemented a pharmacy-driven POS therapeutic monitoring program. Our primary objective was to see if pharmacy intervention can be helpful in optimizing attainment of therapeutic POS levels. Forty-eight steady-state plasma trough POS levels (33 in HSCT pts, 15 in pts undergoing acute leukemia therapy) performed after at least 7 days of administration were analyzed. POS levels were >700 ng/ml in 19/48 (40%) pts. Mean POS level was 790 ng/ml (range 53- 2960), and median was 602 ng/ml. Of the 29 levels <700ng/ml, there were 26 dose modifications. POS was changed to another antifungal in 13 pts, POS was discontinued in 2 pts, and dose was increased in 11 pts. Of the 11 increased doses, 8 follow up levels were drawn with 4 pts achieving a documented therapeutic level. POS was being used as prophylaxis (starting dose 200mg TID) in 31 pts (65%) and empirically (starting dose 400mg BID) in 17 pts (35%). The highest dose used was 400mg QID in one pt with documented fungal infection. GVHD was present in 16 of 33 HSCT pts (48%), and ten of the pts had gut GVHD at the time of level. POS levels were >700ng/mL in 6/16 (38%) and 2/10 (20%) of all GVHD and gut GVHD pts, respectively, although this was not statistically signficant. Proton-pump inhibitor or H2 antagonist therapy (PPI/H2) was administered concurrently with 42/48 (88%) of levels, although the use of these drugs had no apparent effect on therapeutic levels. Leukemia pts were significantly less likely to achieve therapeutic POS levels when compared to HSCT pts (27% vs 61%, p = 0.029). Other than treatment group, we found no other factors that correlated with achieving therapeutic levels. The pharmacy based implementation of POS therapeutic monitoring revealed that achievement of recommended POS levels remains a challenge in an unselected HSCT and leukemic population. This program enabled documentation of compliance and allowed an attempt at improvement of POS levels by dose adjustment. Pharmacists counseled pts on ways to increase absorption by taking with a high fat meal, nutritional supplement, or acidic carbonated beverage, and by stopping their PPI/H2.