Efficacy and safety of Voriconazole in immunocompromised patients – single centre experience

Abstract

Background

Data on epidemiology and survival after fungal infections in patients with cancer are primarily based on studies in adults, whereas few data are available on children.

Aim

The objective of this study was to determine the safety and tolerability of the oral and i.v. formulations of voriconazole Vfend®, previously not reported in Poland.

Materials/Methods

Twenty consecutive children and young adults aged 1 to 25 years, submitted for blood and marrow transplantation (BMT), were recruited during 10 months. When suspected or verified breakthrough systemic fungal infection occurred while kept on primary prophylactic fluconazole regimen, all patients received two loading doses of i.v. or oral voriconazole 6–9 mg/kg every 12 hrs, followed by a maintenance dose of 3 mg/kg every 12 hrs for five doses. If well tolerated, the voriconazole dosage was increased to 4 mg/kg every 12 hrs thereafter.

Results

Fungal infection was possible in 15/20, organ involvement with pulmonary process in 13 pts; CNS changes in 2 pts. Fungal aetiology was proven in 3 children (pulmonary Aspergillosis in 2 and Candida krusei in 1 patient), and considered as probable in 2 patients, having lung (2) and CNS (1) involvement. Four patients died. Clinical and radiological improvement was obtained in 14 patients, while uncontrolled, progressive disease occurred in 1 patient. Transient visual disturbances occurred in one patient. Major caution is warranted due to drug interaction via the cytochrome P-450 system which may lead to unexpected toxicity of the coadministered drugs (e.g. Vinca alkaloids, cyclosporine, rifampicin, erythromycin, etc).

Conclusions

Voriconazole is an advantageous new azole well tolerated in 20 patients. Outcome in BMT breakthrough infections was good.