Evaluation of Posaconazole Serum Concentrations from Delayed-Release Tablets in Patients at High-Risk for Fungal Infections [PublishAheadOfPrint]

Purpose: To determine the frequency of patients who achieved a therapeutic drug level after receiving posaconazole (PCZ) delayed release tablets (DRT) for prophylaxis or treatment of invasive fungal infections (IFIs), and to examine the effect of demographic traits and treatment characteristics on PCZ serum levels

Methods: A retrospective single-center study was conducted on high-risk inpatients at the University of Washington Medical Center (UWMC) that obtained PCZ for either treatment or prophylaxis from August 1^st 2014 and August 31^st, 2015. High-risk patients were defined as those undergoing chemotherapy for a primary hematologic malignancy and those undergoing hematopoietic cell (HCT) or solid organ transplantation. Serum trough concentrations of ≥700 mcg/L and ≥1,000 mcg/L were considered appropriate for prophylaxis and treatment respectively.

Results: The most frequent underlying medical condition was a hematological malignancy (43/53, 81%). 26/53 (49%) received PCZ for prophylaxis, the rest for treatment. A total of 37/53 (70%) had PCZ serum levels ≥700 mcg/L regardless of indication, including 22/26 (85%) that received PCZ for prophylaxis. Of the patients that received PCZ for treatment, only 12/27 (44%) had PCZ serum levels ≥1,000 mcg/L. The odds of having therapeutic PCZ serum levels were not statistically different in patients with a weight ≥90kg, diarrhea grade ≥2, mucositis grade ≥2, or poor dietary intake. However, the odds of having therapeutic PCZ serum levels was 5.85 times higher in patients without graft-versus-host disease (GVHD) treatment compared to those with GVHD treatment. Four patients on prophylaxis (15%) developed breakthrough invasive fungal infections, one of which had a subtherapeutic level.

Conclusion: Use of PCZ DRT provides adequate concentrations in only 70% of our patients and recommended dosing may lead to insufficient levels in patients treated for IFIs. Lower concentrations noted among high-risk patients with GVHD suggest a need for prospective studies evaluating therapeutic drug monitoring and/or dose adjustments among these patients.

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