Liver Safety of Posaconazole in Early Salvage Therapy for Invasive Fungal Infections Caused by Molds and Yeasts

SHARIQ HAIDER, MICHEL LAVERDIèRE, COLEMAN ROTSTEIN, SHAHID HUSAIN, KAREN DOUCETTE, MARYSE POWER, JEFFREY LIPTON, PETER PHILLIPS, ANDRE GALARNEAU and JEAN-FRANCOIS POULIOT

Author address: 

Juravinski Hospital and Juravinski Cancer Center, Hamilton, ON, Canada

Abstract: 

Background: Long term survival of immunocompromised patients has improved considerably over the last few decades. However, this also led to an increase in invasive fungal infections (IFIs). Several commonly used agents can effectively treat, but long term use may be associated with toxicity that can compromise patient safety and adherence to therapy. Posaconazole is a second generation antifungal agent with wide yeast and mold coverage that possess a favorable safety profile Methods: This single arm study of posaconazole (400 mg BID) included patients who failed, or were intolerant to, one prior line of antifungal therapy. Forty patients were enrolled in 8 centers across Canada from March 2008 to May 2011. The primary objectives were safety and efficacy. Liver toxicity was specifically assessed because 50% of patients had at least one elevated liver enzyme at study. Results: Of the 40 patients included in the study, 29 (73%) had proven or probable (PP) IFIs. Response based on the EORTC criteria in PP patients was 50% (7% CR and 43% PR). Conditions to IFI were leukemia (34%), stem cell transplant (27%), lung and renal transplant (23%) and others (16%). Indentified organisms included Aspergillus (61%), Candida (18%), Z ygomycetes (12%), and other rare molds (6%). Safety was assessed in all 40 patients and common toxicities reported were nausea & vomiting (26%), diarrhea (26%), rash (15%), and edema (12%). No drug-related grade 4 toxicities were reported. Twenty patients entered the study with elevated liver enzyme after receiving voriconazole (70%), amphotericin B (20%), fluconazole (5%) and caspofungin (5%). Seven patients had liver enzyme elevation after initiation of Posaconazole therapy. In most patients this effect was transient; and only 3 patients still had elevated enzymes at week 12. All were lower than 2X the upper limit of normal. Conclusion: Posaconazole (400 mg BID) was effective in 50% of IFI patients who were treatment-refractory or intolerant to prior antifungal. Posaconazole was also associated with a favorable toxicity profile especially in terms of liver enzymes irrespective of prior therapy. Posaconazole represents a clinically useful early salvage therapy for immunocompromised patients refractory or intolerant to prior antifungals.
2012

abstract No: 

223

Full conference title: 

ID Week 2012
    • IDWeek 2012