Background and Importance Voriconazole is an antifungal agent with concentration-dependent activity and high individual variability. It is generally well tolerated. However, adverse effects (AEs) may occur, requiring dose reduction (DR) or discontinuation of treatment.

Aim and Objectives To describe the safety and tolerability of voriconazole treatment in a cohort of patients admitted to a tertiary hospital.

Material and Methods Retrospective observational cohort study that included patients treated with voriconazole during 2022.

Variables collected were age, sex, diagnosis, route of administration, treatment start date, date and type of AEs, post-AE measures, and therapeutic drug monitoring (TDM).

Voriconazole AEs were classified as concentration-dependent or non-concentration-dependent.

Results A total of 135 patients were treated with voriconazole. The median age was 64 years (4–91). Men represented 61%. Most patients were immunocompromised (42%).

Treatment was empiric in 21%, prophylaxis in 10% and targeted therapy in 69%. The main diagnosis was Aspergillus (81%), 11% Candida and 8% other infections. It was administered intravenously in 45%, orally in 30%, and 25% were switched from intravenous to oral. The median duration of treatment was nine days.

Voriconazole-related AEs occurred in 38 patients (28%). The median time to AE onset was five days.

Concentration-related AEs were hepatotoxicity in seven patients (18%), visual disturbances in 11 patients (29%), psychiatric disorders in 12 patients (31%) such as hallucinations (10) or confusional syndrome (2) and neurologic disturbances in 12 patients (31%) who experienced somnolence (4), vivid dreams (4), tremor (3) or disorientation (3). Four patients required DR and 10 discontinued treatment.

Non-concentration-related AEs were dermatologic reactions in eight patients (21%), including photosensitivity (3), alopecia (2), erythema (4), or warm sensation (4), and digestive disorders (diarrhoea) in one patient. Two patients discontinued treatment.

Of 38 patients with AEs, 22 (58%) had voriconazole TDM: 17 had therapeutic concentrations, two infratherapeutic and three supratherapeutic, of whom two tolerated treatment with DR and one discontinued voriconazole for other reasons.

Conclusion and Relevance Approximately 1 in 3 patients experienced AEs. The most common AEs were visual disturbances and hallucinations. We cannot confirm that these AEs were due to supratherapeutic concentrations as 45% had concentrations in the therapeutic range but TDM may be an interesting strategy to improve tolerability to voriconazole.

Conflict of Interest No conflict of interest.