The utility of voriconazole therapeutic drug monitoring in a multi-racial cohort in Southeast Asia

Abstract Introduction 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 to Caucasians and East Asians. Hence, there are concerns for higher risk of voriconazole accumulation and toxicity. Objectives 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. 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 (15.7%) patients experienced hepatotoxicity (troughs 0.5->7.5 mg/L). Neurotoxicity occurred in 3 (4.3%) patients (troughs ≥6.7 mg/L) and saw symptom resolution upon dose reduction. Treatment failure of invasive fungal infection appeared less in patients with therapeutic troughs compared to sub-therapeutic troughs (11.4% vs 14.2%). Two patients experienced treatment failure despite supra-therapeutic voriconazole troughs. 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.