Background and importance Voriconazole has shown high interpatient variability in plasma steady state trough concentration (C_trough). It presents a narrow therapeutic range, with C_trough <1 µg/mL, related to treatment failure, and >4 µg/mL with toxicity.

Aim and objectives To describe plasma voriconazole concentrations (PVC) in an adult cohort treated in a tertiary university hospital. Also, to identify potential causes of interpatient variability in C_trough and to find an association between clinical outcomes and adverse events (AE) with PVC.

Material and methods This was an observational retrospective study with no intervention. All patients with a determination of PVC during 2017 were included. Data were obtained from the electronic medical records.

Results A total of 165 C_trough were analysed from 51 patients (60.8% men). Median age and weight were 65.2 years (IQR 54.5–71.3) and 70.0 kg (IQR 62.0-81.0), respectively. Ten patients (19.6%) had a body mass index >30 kg/m², 6 (11.8%) had a drinking history and 1 patient suffered from liver failure. Voriconazole treatment indication was invasive fungal infection in most patients (80.4%), candidaemia (9.8%) and other (9.8%). Median voriconazole dose was 5.8 mg/kg (IQR 4.9-6.6) and median treatment duration was 140 days (IQR 65-176).

Reasons for treatment discontinuation were cure/negative culture (42.8%), appearance of drug related AE (16.4%), treatment inefficacy (9.1%) and other (30.9%). Co-medication with steroids was present in 71 cases (45.0%) and only one significant drug–drug interaction was reported (rifampin).

Median C_trough was 2.4 µg/mL (IQR 1.4–3.6). C_trough values were <1 µg/mL in 26 cases (15.8%) and >4 µg/mL in 34 (20.6%). From these, the dose was adjusted in 10 and 5 cases, respectively, resulting in 66.7% of the time that the next PVC was within the recommended range.

We observed a trend towards higher PVC in patients reporting AE (p=0.177) and lower in alcoholic patients (p=0.053). Within those cases with a C_trough <1 µg/mL, co-treatment with corticosteroids and women showed significantly lower plasma values (p=0.015 and p=0.052, respectively).

Conclusion and relevance We confirmed high variability in voriconazole C_trough in routine clinical practice. Co-treatment with corticosteroids, women and alcoholic patients were factors related to lower C_trough values. Thus in these patients, it might be suitable to perform therapeutic voriconazole monitoring in clinical practice to help optimise antifungal treatment.

References and/or acknowledgements 1. Int J Clin Pharmacol Ther 2018;56:239–246.

No conflict of interest.