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

doi:10.1086/504328

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

Internal Medicine

Research output: Contribution to journal › Article › peer-review

198 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 language	English
Pages (from-to)	1726-1734
Number of pages	9
Journal	Clinical Infectious Diseases
Volume	42
Issue number	12
DOIs	https://doi.org/10.1086/504328
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1086/504328

Cite this

Raad, I. I., Graybill, J. R., Bustamante, A. B., Cornely, O. A., Gaona-Flores, V., Afif, C., Graham, D. R., Greenberg, R. N., Hadley, S., Langston, A., Negroni, R., Perfect, J. R., Pitisuttithum, P., Restrepo, A., Schiller, G., Pedicone, L., & Ullmann, A. J. (2006). Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections. Clinical Infectious Diseases, 42(12), 1726-1734. https://doi.org/10.1086/504328

@article{93e791da412a4760983b790e75eae4ca,

title = "Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections",

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.",

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

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{\textquoteright} 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{\textquoteright} 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{\textquoteright} 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{\textquoteright} 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{\textquoteright} 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{\textquoteright} bureaus for Schering-Plough, MSD, Pfizer, Astellas, and Gilead. All other authors: no conflicts.",

year = "2006",

month = jun,

day = "15",

doi = "10.1086/504328",

language = "English",

volume = "42",

pages = "1726--1734",

number = "12",

}

Raad, II, Graybill, JR, Bustamante, AB, Cornely, OA, Gaona-Flores, V, Afif, C, Graham, DR, Greenberg, RN, Hadley, S, Langston, A, Negroni, R, Perfect, JR, Pitisuttithum, P, Restrepo, A, Schiller, G, Pedicone, L & Ullmann, AJ 2006, 'Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections', Clinical Infectious Diseases, vol. 42, no. 12, pp. 1726-1734. https://doi.org/10.1086/504328

TY - JOUR

T1 - Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections

AU - Raad, Issam I.

AU - Graybill, John R.

AU - Bustamante, Ana Beatriz

AU - Cornely, Oliver A.

AU - Gaona-Flores, Veronica

AU - Afif, Claude

AU - Graham, Donald R.

AU - Greenberg, Richard N.

AU - Hadley, Susan

AU - Langston, Amelia

AU - Negroni, Ricardo

AU - Perfect, John R.

AU - Pitisuttithum, Punnee

AU - Restrepo, Angela

AU - Schiller, Gary

AU - Pedicone, Lisa

AU - Ullmann, Andrew J.

N1 - 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.

PY - 2006/6/15

Y1 - 2006/6/15

N2 - 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.

AB - 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.

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JF - Clinical Infectious Diseases

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ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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