1445. Posaconazole Serum Concentrations for Salvage Treatment and Prevention of Invasive Fungal Infections in Immunocompromised Patients
Session: Poster Abstract Session: Fungal Infections
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Background: Posaconazole (PCZ) is a triazole antifungal used for salvage treatment (Tx) and prophylaxis (Px) of invasive fungal infections (IFI) in immunocompromised patients. Inter-patient pharmacokinetic profiles are variable and data on therapeutic drug monitoring remains limited. The aim of this study is to evaluate PCZ levels associated with Tx response and IFI breakthrough prevention in immunocompromised patients.

Methods: A retrospective chart review evaluating PCZ for Tx and Px was performed, including patients ≥18 years old with steady state PCZ levels between 2008 and 2011. Data was collected on baseline characteristics, 90-day response (complete or partial response) for Tx of proven and probable IFI, presence of breakthrough IFI for Px, patient-specific factors affecting PCZ levels, and adverse reactions.  

Results: 126 patients were evaluated with 99/126 patients assessed for Tx (N=26) and Px (N=73). For Tx, 15/26 (58%) patients had acute leukemia and 16/26 (62%) patients underwent hematopoietic cell transplant. 14/26 (54%) patients responded. The mean PCZ level of those who responded was 0.70mcg/mL versus 0.28mcg/mL of those who did not respond (p=0.03). 5/5 (100%) patients with a level ≥0.8mcg/mL and 9/21 (43%) patients with a level <0.8mcg/mL responded (p=0.04). For Px, 37/73 (51%) patients had acute leukemia and 70/73 (96%) patients underwent hematopoietic cell transplant. The mean level of 66 patients with no breakthrough was 0.58mcg/mL versus 0.36mcg/mL of the 7 patients with IFI breakthrough (p=0.27). 1/27 (4%) patients with a level ≥0.6mcg/mL and 6/46 (13%) patients with a level <0.6mcg/mL experienced a breakthrough (p=0.25). Factors associated with lower PCZ levels were poor oral diet (p<0.0001) and acid suppression (p=0.02). 17/126 (13%) patients reported adverse drug reactions, which were not associated with PCZ levels. 

Conclusion: Therapeutic drug monitoring is important for patients receiving PCZ salvage Tx and Px. For Tx, PCZ levels ≥0.8mcg/mL were significantly associated with response. For Px, PCZ levels ≥0.6mcg/mL appeared to be associated with less IFI breakthrough, but not statistically significant. Patients should be monitored for decreased PCZ absorption with poor diet and use of acid suppression.

Aimee Keegan, PharmD, James Ito, MD, Bernard Tegtmeier, PhD, Sanjeet Dadwal, MD and Jane Kriengkauykiat, PharmD, City of Hope, Duarte, CA

Disclosures:

A. Keegan, None

J. Ito, None

B. Tegtmeier, None

S. Dadwal, None

J. Kriengkauykiat, None

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