Voriconazole-induced hypokalemia and hyponatremia and their correlations with voriconazole trough concentration

Objective To investigate the incidence rates of voriconazole-induced hypokalemia and hyponatremia and their correlations with voriconazole trough concentration in the patients with lung invasive aspergillosis. Methods The clinical data of the patients receiving therapeutic drug monitoring for voriconazole due to lung invasive aspergillosis in our hospital from 8 October, 2017 to 30 April, 2019 were collected and retrospectively analyzed. Sex, age, body weight, baseline diseases, types of fungal infection, route of administration, daily voriconazole dose, voriconazole trough concentration, serum potassium and sodium concentrations, and the times of hypokalemia and hyponatremia after administration were collected in all the patients. The relationships of voriconazole trough concentration with serum potassium and sodium concentrations were analyzed with Pearson's correlation analysis. Results A total of 142 patients with lung invasive aspergillosis were enrolled, with 267 voriconazole trough concentrations. The patients were mainly men (64.1%). Their mainly baseline diseases were majorly leukaemia (26.8%) and hypertension (32.4%), followed by diabetes mellitus, chronic obstructive pulmonary disease, kidney transplantation, and coronary atherosclerotic heart disease. The most common infected fungus was Aspergillus (40.8%). The voriconazole trough concentration was 2.9 (1.6, 4.9) μg/mL, with a range of 0.4~15.5 μg/mL among the patients, 42 patients suffered from hypokalemia, accounting for 29.6%, and 21 patients suffered from hyponatremia, accounting for 14.8%. Hypokalemia and hyponatremia were mainly observed in 1 to 5 d after voriconazole administration, accounting for 57.1% and 42.9%, respectively. Most of the patients with hypokalemia and hyponatremia received the agent through intravenous injection. The duration of hypokalemia after oral administration was long, while the time with intravenous injection was short. There were no correlations of voriconazole trough concentration with serum potassium and sodium (r=0.001, P=0.989; r=0.150, P=0.052). Conclusion Under routine dose, the incidences of hypokalemia and hyponatremia are quite high after intravenous injection of voriconazole, and they mainly occur in the early time after administration. Special attention should be paid to the adverse effects in clinical practice.