Efficacy and Safety of Voriconazole in the Treatment of Acute Invasive Aspergillosis

Abstract

To evaluate the efficacy and safety of voriconazole in acute invasive aspergillosis (IA), an open, noncomparative multicenter study was conducted. Immunocompromised patients with IA were treated with intravenously administered voriconazole 6 mg/kg twice a day (b.i.d.) twice and then 3 mg/kg b.i.d. for 6-27 days, followed by 200 mg b.i.d. administered orally for up to 24 weeks. Response was assessed by clinical and radiographic change. A total of 116 patients were assessable. IA was proven in 48 (41%) and probable in 68 patients. Voriconazole was given as primary therapy in 60 (52%). Good responses were seen in 56 (48%); 16 (14%) showed complete response and 40 (34%) partial response. A stable response was seen in 24 patients (21%), and 36 (31%) of the infections failed to respond to therapy. Good responses were seen in 60% of those with pulmonary or tracheobronchial IA (n=84), 16% with cerebral IA (n=19), 58% with hematologic disorders (n=67), and 26% of allogeneic stem cell transplant recipients (n=23). Voriconazole is efficacious in treating acute IA.

Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study

“…In other recent studies, patients with proven invasive aspergillosis had a worse outcome, 21 or, in complete contrast, a better outcome than patients with probable invasive aspergillosis. 22 Standard anti-fungal prophylaxis was based on fluconazole or itraconazole, given that posaconazole had not been approved for prophylaxis in Italy when the study was on-going. About two-thirds of the patients in our series developed invasive aspergillosis despite prior antiAspergillus prophylaxis.…”

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

“…and oral formulations, with excellent oral bioavailability 61 and highly variable nonlinear pharmacokinetics. [62][63][64] Excretion of voriconazole occurs predominantly via metabolites in the urine, with limited faecal excretion. 65 Voriconazole has moderate plasma protein binding, but there are limited data on the interaction of voriconazole with the various drug transporters.…”

Fungal Infections in Transplant and Oncology Patients

“…In addition, response appears to be lower among patients with IA and low mean voriconazole plasma levels (<0.25 μg/ml). Because of these issues, voriconazole levels should be monitored during therapy [95].…”

“…In addition, response appears to be lower among patients with IA and low mean voriconazole plasma levels (<0.25 μg/ml). Because of these issues, voriconazole levels should be monitored during therapy [95].The appropriate choice for therapy in the setting of voriconazole intolerance or failure is a subject of debate. Current Infectious Diseases Society of America (IDSA) guidelines for treatment of IA include echinocandins (caspofungin and micafungin) as an option for salvage therapy, along with lipid formulations of amphotericin B, itraconazole, and posaconazole [92].…”