Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections.
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 > or = 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 > or = 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.
Raad
Issam I
II
The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. iraad@mdanderson.org
Graybill
John R
JR
Bustamante
Ana Beatriz
AB
Cornely
Oliver A
OA
Gaona-Flores
Veronica
V
Afif
Claude
C
Graham
Donald R
DR
Greenberg
Richard N
RN
Hadley
Susan
S
Langston
Amelia
A
Negroni
Ricardo
R
Perfect
John R
JR
Pitisuttithum
Punnee
P
Restrepo
Angela
A
Schiller
Gary
G
Pedicone
Lisa
L
Ullmann
Andrew J
AJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000473:pathology*; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use
D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole