Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections

Issam I. Raad, John R. Graybill, Ana Beatriz Bustamante, Oliver A. Cornely, Veronica Gaona-Flores, Claude Afif, Donald R. Graham, Richard N. Greenberg, Susan Hadley, Amelia Langston, Ricardo Negroni, John R. Perfect, Punnee Pitisuttithum, Angela Restrepo, Gary Schiller, Lisa Pedicone, Andrew J. Ullmann

Research output: Contribution to journalArticlepeer-review

196 Scopus citations

Abstract

Background. Invasive fungal infections are found most frequently in immunosuppressed and critically ill hospitalized patients. Antifungal therapy is often required for long periods. Safety data from the clinical development program of the triazole antifungal agent, posaconazole, were analyzed. Methods. A total of 428 patients with refractory invasive fungal infections (n = 362) or febrile neutropenia (n = 66) received posaconazole in 2 phase II/III open-label clinical trials. Also, 109 of these patients received posaconazole therapy for ≥6 months. Incidences of treatment-emergent, treatment-related, and serious adverse events and abnormal laboratory parameters were recorded during these studies. Results. Treatment-emergent, treatment-related adverse events were reported in 38% of the overall patient population. The most common treatment-related adverse events were nausea (8%) and vomiting (6%). Treatment-related serious adverse events occurred in 8% of patients. Low rates of treatment-related corrected QT interval and/or QT interval prolongation (1%) and elevation of hepatic enzymes (2%) were reported as adverse events. Treatment-emergent, treatment-related adverse events occurred at similar rates in patients who received posaconazole therapy for <6 months and ≥6 months. Conclusions. Prolonged posaconazole treatment was associated with a generally favorable safety profile in seriously ill patients with refractory invasive fungal infections. Long-term therapy did not increase the risk of any individual adverse event, and no unique adverse event was observed with longer exposure to posaconazole.

Original languageEnglish
Pages (from-to)1726-1734
Number of pages9
JournalClinical Infectious Diseases
Volume42
Issue number12
DOIs
StatePublished - Jun 15 2006

Bibliographical note

Funding Information:
Potential conflicts of interest. I.I.R. has received recent research funding from Schering-Plough and Wyeth-Ayerst; serves as a consultant for Vicuron and Peninsula Pharmaceuticals; and is on the speakers’ bureaus for Merck, Pfizer, Astellas, and Wyeth-Ayerst. J.R.G. has received research grants from Merck, Schering-Plough, NeuTech Pharma, Astellas, and Pfizer and has performed research work for Indevus; is on advisory committees for Merck, Schering-Plough, Indevus, and Pfizer; and is a speaker for Merck. A.B.B. has received research funding from Fujisawa Healthcare and No-vartis. O.A.C. has received research funding from, is a consultant for, and is a member of speakers’ bureaus for Astellas, Gilead, Merck, Pfizer, and Schering-Plough; has received research funding from and is a consultant for Basilea and Vicuron; and is a consultant for Zeneus. D.R.G. has received recent research funding from Vicuron, Wyeth, Schering-Plough, and Pfizer; is a consultant for Vicuron and Wyeth; and is on the speakers’ bureaus for Wyeth, Pfizer, and Aventis. R.N.G. has received recent research funding from Boehringer Ingelheim, BMS, Schering-Plough, Merck, Dynport, Acambis, Vaxgen, Bavarian-Nordic, Astellas, GSK, Tibotec, and VirXsys. S.H. has received recent research funding from Enzon (formerly The Liposome Company), Astellas (formerly Fujisawa), Ortho-Biotech, Pfizer, and Schering-Plough and is a consultant for Schering-Plough, Merck, and Enzon. S.H. is on the speakers’ bureaus for Merck, Pfizer, and Astellas. A.L. has received research funding and is a consultant for Schering-Plough. J.R.P. has received research funding from, is a consultant for, and is on the speakers’ bureaus for Merck, Astellas, Pfizer, Schering-Plough, Enzon, and Pliva. G.S. is a consultant for Wyeth-Ayerst, CI, and Johnson & Johnson. L.P. is an employee of Schering-Plough. A.J.U. has received recent research funding from Schering-Plough and is a consultant for Schering-Plough, MSD, Pfizer, Astellas, Gilead, and Basilea. A.J.U. is on the speakers’ bureaus for Schering-Plough, MSD, Pfizer, Astellas, and Gilead. All other authors: no conflicts.

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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