Voriconazole therapeutic drug monitoring: results of a prematurely discontinued randomized multicenter trial

• Published in: Transplant infectious disease 2015-12, Vol.17 (6), p.831-837
• Main Authors: Neofytos, D., Ostrander, D., Shoham, S., Laverdiere, M., Hiemenz, J., Nguyen, H., Clarke, W., Brass, L., Lu, N., Marr, K.A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antifungal Agents - adverse effects; Antifungal Agents - blood; Antifungal Agents - therapeutic use; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Middle Aged; therapeutic drug monitoring; transplant monitoring; voriconazole; Voriconazole - adverse effects; Voriconazole - blood; Voriconazole - therapeutic use
• ISSN: 1398-2273; 1399-3062
• DOI: 10.1111/tid.12454

Background Voriconazole (VOR) levels are highly variable, with potential implications to both efficacy and safety. We hypothesized that VOR therapeutic drug monitoring (TDM) will decrease the incidence of treatment failures and adverse events (AEs). Methods We initiated a prospective, randomized, non‐blinded multicenter study to compare clinical outcomes in adult patients randomized to standard dosing (clinician‐driven) vs. TDM (doses adjusted based on levels). VOR trough levels were obtained on day 5, 14, 28, and 42 (or at completion of drug; ± 3 days). Real‐time dose adjustments were made to maintain a range between 1–5 μg/mL on the TDM‐arm, while levels were assessed retrospectively in the standard‐arm. Patient questionnaires were administered to assess subjective AEs. Results The study was discontinued prematurely, after 29 patients were enrolled. Seventeen (58.6%) patients experienced 38 AEs: visual changes (22/38, 57.9%), neurological symptoms (13/38, 34.2%), and liver abnormalities (3/38, 7.9%). VOR was discontinued in 7 (25%) patients because of an AE (4 standard‐arm, 3 TDM‐arm). VOR levels were frequently out of range in the standard‐arm (8 tests >5 μg/mL; 9 tests