Background Voriconazole is an antifungal drug used for invasive fungal infection with high pharmacokinetic variability and narrow therapeutic range and, therefore, therapeutic drug monitoring (TDM) is recommended.

Purpose The objective was to evaluate the standard dosage regimen of voriconazole in a paediatric and adult population through TDM.

Material and methods Retrospective observational study (January 2015 and October 2017). Inclusion criteria: adult and paediatric patients treated with voriconazole (oral/intravenous) with at least one trough plasma concentrations (C_trough) of voriconazole at steady state (>5 days) with the standard dosage and without concomitant use of potent inducers or inhibitors. Standard dose was: paediatric 8 mg/kg IV BID or 9 mg/kg PO BID, and adult 4 mg/kg IV BID or 200 mg PO BID. Variables: age, weight, indication (treatment or prophylaxis) and C_trough at steady state. Data was stratified by paediatric and adult patients. Primary outcome was: percentage of patients with C_trough at steady state of voriconazol within the therapeutic range at the standard dose (therapeutic window by indication: treatment: 1–5 mg/L; prophylaxis: 0.5–5 mg).

Results A total of 56 patients were included (26.7% children and 73.2% adults). In the paediatric group, the mean age and weight was 6.4 years (95% CI: 3.9 to 9.0) and 25.5 kg (95% CI: 16.4 to 34.5). The mean age and weight for the adult patients were 61.0 years (95% CI: 56.4 to 65.6) and 69.9 kg (95% CI: 65.3 to 74.5). 17.7% of the patients were treated with voriconazole for prophylaxis and 82.2% for treatment.

The median C_trough in paediatrics was lower than in adults: 0.7 mg/L (p25–75: 0–5.5) vs 2.5 mg/L (p25–75: 0.1–8.0), respectively (p<0.05).

66.7% and 22% of patients had infra-therapeutic C_trough in paediatrics and adults (p<0.05), respectively. However, C_trough above the therapeutic window was similar between groups (6.7% of paediatrics and 7.3% of adults).

Conclusion The C_trough with the standard maintenance dose of voriconazol were within the therapeutic range in only 26.7% in paediatrics, while in the adult group it was 70.7%. Given the high variability observed in the C_trough, it was necessary to perform TDM at the beginning of the treatment to make an individualised dosage adjustment in both paediatric and adult patients.

References and/or acknowledgements https://www.ema.europa.eu/documents/product-information/vfend-epar-product-information_es.pdf

No conflict of interest.