JAC Advance Access originally published online on October 3, 2008
Journal of Antimicrobial Chemotherapy 2008 62(6):1386-1391; doi:10.1093/jac/dkn401
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Original research |
Posaconazole as salvage treatment of invasive fungal infections in patients with underlying renal impairment
1 Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Department of Bone Marrow Transplantation, Emory University Hospital, Atlanta, GA, USA 3 Department of Medicine, Chief, Division of Infectious Diseases, University of Texas Health Science Center, San Antonio, TX, USA 4 Department of Medicine, Division of Infectious Diseases, Duke University Mycology Research Unit, Durham, NC, USA 5 Schering-Plough Research Institute, Kenilworth, NJ, USA
Received 23 May 2008; returned 3 July 2008; revised 22 August 2008; accepted 2 September 2008
* Corresponding author. Tel: +1-713-792-4389; Fax: +1-713-792-8233; E-mail: rhachem{at}mdanderson.org
Objectives: The aim of this study is to determine the efficacy and safety of posaconazole in patients with underlying renal impairment.
Patients and methods: We analysed the efficacy and safety of posaconazole in patients with renal impairment in a post hoc subanalysis of a Phase 3, multicentre, open-label trial in patients with invasive fungal infections (IFIs). In the Phase 3 study, 330 patients intolerant of or with IFIs refractory to standard antifungal therapy received posaconazole 800 mg daily in divided doses. In our subanalysis, 238 patients with proven/probable IFIs, including 65 patients with renal impairment (creatinine clearance < 50 mL/min or serum creatinine (sCR) level >2 mg/dL at baseline) and 173 patients with greater renal function [creatinine clearance 
50 mL/min (acceptable renal function)], formed the modified intent-to-treat population. Success was defined as complete or partial response, and non-success was defined as stable disease or treatment failure.
Results: Overall response rates were similar in the renal impairment group (49%) and in the acceptable renal function (50%) group. Seventeen of the 41 patients with renal impairment and aspergillosis responded. Adverse events occurred in 32/65 (49%) patients with renal impairment and in 72/173 (42%) patients with acceptable renal function. The most common adverse events in both groups were nausea (14% patients with renal impairment versus 8% with acceptable renal function), altered/elevated levels of other medications (8% versus 2%), increased sCR levels (6% versus 0%), vomiting (6% versus 4%), abdominal pain (5% versus 5%) and dizziness (5% versus 1%).
Conclusions: These results suggest that posaconazole is effective and well tolerated in patients with refractory IFIs regardless of renal impairment.
Keywords: refractory IFIs , aspergillosis , antifungals , azoles