| Exclusion Criteria: | 1) Women who are pregnant or breastfeeding.
2) Known history of allergy, hypersensitivity to or any serious reaction to the azole class of antifungals or to any component of the study medication.
3) Patients for whom VRC is contra-indicated, including cardiovascular findings.
4) Patients at high risk for QT/QTc prolongation such as: 1) Baseline prolongation of QTcF ³ 500 msec. 2) Risk factors for Torsade de Pointes (e.g. uncompensated heart failure, abnormal potassium or magnesium levels that cannot be corrected, any unstable cardiac condition during the last 30 days, or a family history of long QT syndrome). 3) The use of concomitant medications that prolong the QT/QTc interval.
5) Evidence of moderate to severe hepatic or renal dysfunction with any of the following abnormal laboratory parameters at the screening visit: (1) Total bilirubin is equal to or more than 3 times the upper limit of normal (ULN); (2) Alanine transaminase (ALT) or aspartate transaminase (AST) is equal to or more than 5 times ULN; (3) Patients with known cirrhosis or chronic hepatic failure. 4) Calculated creatinine clearance (CLcr) < 50 mL/minute at screening 5) Patients on dialysis or likely to require dialysis while on medication.
6) Concomitant use of sirolimus, efavirenz, ritonavir, astemizole, cisapride, rifampicin, rifabutin, ergot alkaloids, long acting barbiturates, carbamazepine, pimozide, quinidine, neostigmine, ketoconazole, valproic acid, St. John's Wort or terfenadine, in the 5 days prior to first administration of study drug .
7) Patients with any other invasive fungal infection other than Aspergillus species or other filamentous fungi and patients with Zygomycetes or Scedosporium prolificans infection not expected to respond to voriconazole treatment.
8) Patients with either chronic aspergillosis, aspergilloma, or ABPA.
9) Microbiological (e.g. virological) findings or other potential conditions that are temporally related and suggest a different etiology of the clinical features.
10) Patients who have been administered more than 4 cumulative days of itraconazole, voriconazole, or posaconazole, for any reason, within the 7 days prior to the first administration of study medication.
11) Advanced human immunodeficiency virus infection with CD4 count is less than 200 or acquired immunodeficiency syndrome-defining condition, body weight is less than 40 kg.
12) Any known or suspected condition of the patient that may jeopardize adherence to the protocol requirements or impede the accurate measurement of efficacy (e.g. neutropenia not expected to resolve, patients with endocarditis, osteomyelitis, meningitis, tracheobronchitis, or uncontrolled malignancy with life expectancy of less than 30 days).
13) Patients with a concomitant medical condition that, in the opinion of the investigator, may be an unacceptable additional risk to the patient should he/she participate in the study.
14) Patients previously enrolled in this study.
15) Treatment with any investigational drug in any clinical trial within 30 days prior to the first administration of study medication except unblinded phase III trials.
16) Patients who are unlikely to survive longer than 30 days or patients on mechanical ventilation. |