The utility of voriconazole therapeutic drug monitoring in a multi-racial cohort in Southeast Asia. (June 2020)

• Record Type: Journal Article
• Authors: Zhou, Peijun Yvonne; Lim, Tze Peng; Tang, Si Lin Sarah; Liew, Yixin; Chua, Sy Grace Nathalie; Lim, Li Ling Cheryl; Lee, Hui Ling Winnie; Tan, Si Xuan; Lai, Oi Fah; Tan, Thuan Tong; Wong, Gee Chuan; Kwa, Lay Hoon Andrea
• Is Part Of: Journal of global antimicrobial resistance. Volume 21(2020)
• Page Start: 427
• Page End: 433
• Publication Date: 2020-06
• Subjects: Voriconazole -- Therapeutic drug monitoring -- Invasive fungal infections -- Chronic pulmonary aspergillosis -- Hepatotoxicity -- Neurotoxicity; Drug resistance -- Periodicals; Drug resistance -- Periodicals; Drug resistance; Periodicals; 616.9041
• DOI: 10.1016/j.jgar.2019.12.004
• Languages: English
• ISSNs: 2213-7165

Abstract

Highlights: Majority of patients fail to attain therapeutic voriconazole (VCZ) troughs. TDM should be conducted in patients initiated on VCZ. TDM should be conducted in patients with changes in pharmacokinetic factors. TDM reduces the need to switch VCZ to alternative agents due to adverse events. TDM is useful in ruling out sub-therapeutic levels as a cause of treatment failure. Abstract: Objectives: Voriconazole serum concentration, which is affected by several factors, is associated with treatment response and toxicity. There is paucity of data on voriconazole therapeutic drug monitoring (TDM) among Southeast Asians, who exhibit a higher prevalence of CYP2C19-poor metabolisers compared with Caucasians and East Asians. Hence, there are concerns for higher risk of voriconazole accumulation and toxicity. We aim to determine the utility of voriconazole TDM through establishing: (1) proportion of patients achieving therapeutic troughs without dose adjustments; (2) characterisation of patients with sub-therapeutic, therapeutic and supra-therapeutic levels; (3) appropriate dose titrations/dose required for therapeutic troughs; (4) correlation between troughs and adverse events, treatment response/fungal breakthrough. Patients and methods: A single-centre retrospective analysis of data from adults (≥21 years old) with ≥1 voriconazole trough measured at Singapore General Hospital from 2015 to 2017 was performed. Results: Thirty-two patients (45.7%) among 70 patients achieved therapeutic troughs (defined as 2.0–5.5 mg/L) without dose adjustments. Eleven patients (15.7%) experienced hepatotoxicity (troughs 0.5 to >7.5 mg/L). Neurotoxicity occurred in three patients (4.3%) (troughs ≥6.7 mg/L) and all patients had symptom resolution upon dose reduction. Treatment failure of invasive fungal infection appeared less in patients with therapeutic troughs compared with sub-therapeutic troughs (11.4% vs. 14.2%). Two patients experienced treatment failure despite supra-therapeutic voriconazole troughs. Conclusions: TDM should be implemented due to significant unpredictability in dose exposure. TDM can reduce unnecessary switches to alternatives due to intolerability and rule in the possibility of resistant organisms in the event of treatment failure despite therapeutic troughs, alerting clinicians to switch to alternatives promptly.