Xiao Guirong, Zhang Weidong, Liu Yixian, Fan Ping, Hu Ming, Xu Ting
Objective To explore the effect of clinical pharmacists′ intervention in therapeutic drug monitoring (TDM) of voriconazole on medication safety. Methods The study subjects were inpatients with fungal infection, admitted from January 2019 to June 2020 in the Department of Infectious Diseases, West China Hospital, Sichuan University, who were scheduled to be treated with voriconazole. Using random-cluster method, patients were divided into intervention group and control group based on their doctor medical groups. In the intervention group, clinical pharmacists participated in the whole process of voricona- zole TDM and provided pharmaceutical care, while in the control group, no clinical pharmacists participated in TDM. The percentage of voriconazole-treated patients achieved target trough concentration(1.5-5.5-mg/L), the incidence of adverse reactions, and clinical cure rate between the 2 groups were compared. The timely (within 24-hours) management rate of medication orders containing drugs with interaction by doctors and the detection frequency of blood drug concentration were compared between the 2 groups. Results A total of 303 patients were enrolled in the analysis, including 166 in the intervention group and 137 in the control group. There was no significant difference between the 2 groups in demographic characteristics, liver function indexes, types of fungal diseases, main combined diseases, and the use of drugs with interactions with voriconazole before voriconazole treatment (all P>0.05). After receiving voriconazole, percentage of patients achieved target trough concentration in the intervention group was similar to that in the control group in the first detection [55% (91/166) vs. 50% (69/137), P=0.440] while significantly higher in the last detection[81% (134/166) vs. 47% (65/137), P<0.001]. The total frequency of trough concentration detection in the intervention group and the control group were 403 and 244 respectively. Percentage of detection values consisted with target trough concentration was significantly higher, while percentage of detection values exceeding target trough concentration (>5.5-mg/L) was significantly lower in the intervention group than those in the control group, respectively [63% (254/403) vs. 44% (107/244), P<0.001; 19% (63/403) vs. 22% (54/244), P=0.037)]. The total incidence of voriconazole-related adverse reactions [14% (23/166) vs. 23% (31/137)], the incidence of severe adverse reactions [2% (4/166) vs. 8% (11/137)], and incidence of liver injury [Council for International Organizations of Medical Sciences standard: 8% (13/166) vs. 15% (21/137); International Drug-induced Liver Injury Expert Working Group standard: 2% (4/166) vs. 7% (10/137)] in the intervention group were significantly lower than those in the control group (all P<0.05), and the clinical cure rate was similar in the 2 groups [86% (142/166) vs. 81% (111/137), P=0.291]. In the intervention and control groups, some patients were using drugs which had interactions with voriconazole when starting voriconazole treatment, and the timely management rates of these medication orders were 71% (24/17) and 18% (3/17) respectively, with a statistically significant difference between the 2 groups (P=0.001). The detection frequency of voriconazole trough concentration in the intervention group (2.4 times per patient) was higher than that in the control group (1.8 times per patient), and the proportion of patients with ≥3 detection was significantly higher [38% (63/166) vs. 23% (32/137), P=0.006]. Conclusion The involvement of clinical pharmacists in voriconazole TDM can enlarge the percentage of patients who achieve target trough concentration, improve the timely management rate of medication orders containing drugs with interactions with voriconazole, reduce the incidence of voriconazole-related adverse reactions, and improve medication safety.