Voriconazole to Prevent Systemic Fungal Infections in Children

Children (male or female) ages 2-12 years who require treatment for the prevention of systemic fungal infection. Children who are expected to develop neutropenia lasting for more than 10 days following chemotherapy for one of the following conditions: leukemia, lymphoma, aplastic anemia, or as the preparative regimen for bone marrow transplantation. Patients who are anticipated to live more than 3 months. Females of child-bearing potential (post-menarchal) must have a negative pregnancy test at entry. Informed consent of the parent or legally authorized representative obtained prior to entry. Assent will be obtained from minors capable of understanding. No patients who are receiving and cannot discontinue the following drugs at least 24 hours prior to study start: terfenadine and cisapride (due to the possibility of QTc prolongation). Omegprazole (an inhibitor of CYP2C19) which is known to increase plasma voriconazole levels. No patients who have received the following drugs within 14 days prior to study entry: rifampicin, rifabutin, carbamazepine, phenytoin, nevirapine and barbiturates as these are potent inducers of hepatic enzymes and will result in undetectable levels of voriconazole. No patients who have received astemizole within the previous 60 days. No patients who are taking or are likely to receive any investigational drugs except: used for cancer treatment, antiretroviral agents, and drugs used for treatments of any AIDS defining opportunistic infections. No patients with a history or hypersensitivity to or severe intolerance of azole antifungal agents. No patients who have already been entered onto this protocol once. No patient with medical history or evidence of cardiac arrhythmia. No patients with AST and ALT greater than or equal to 5XULN. No patients with moderate and severe renal impairment (i.e., calculated creatine clearance less than 30ml/min). If creatinine clearance is reduced to less than 30 ml/min at any time during the study, the patient must be discontinued from the study. Creatine clearance will be calculated using the following equation: 0.55 X height (cm)/serum creatinine (mg/dL). Any other condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment.