Background and importance Voriconazole has shown high interpatient variability in plasma steady state trough concentration (Ctrough). It presents a narrow therapeutic range, with Ctrough <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 Ctrough 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 Ctrough 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 Ctrough was 2.4 µg/mL (IQR 1.4–3.6). Ctrough 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 Ctrough <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 Ctrough in routine clinical practice. Co-treatment with corticosteroids, women and alcoholic patients were factors related to lower Ctrough 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.
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