Effect of dose adjustment based on doxofylline blood concentration monitoring on safety of combination of doxofylline injection and terbutaline solution for nebulizationor
10.3760/cma.j.issn.1008-5734.2020.01.007
- VernacularTitle:基于多索茶碱血药浓度监测的剂量调整对该药与特布他林雾化液联用安全性的影响
- Author:
Huibin SUN
1
;
Zhong ZHANG
;
Zheng LIU
;
Huizhi ZHANG
Author Information
1. 暨南大学附属郑州医院/郑州市第二人民医院药务科 450006
- Publication Type:Journal Article
- Keywords:
Bronchodilator agents;
Drug monitoring;
Drug-related side effects and adverse reactions;
Doxofylline;
Terbutaline
- From:
Adverse Drug Reactions Journal
2020;22(1):32-37
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of dose adjustment based on doxofylline blood concentration monitoring on safety of combination of doxofylline and terbutaline for respiratory diseases.Methods:The subjects were selected from patients who received doxofylline injection, terbutaline sulphate solution for nebulizationor, and the combination of the two drugs and hospitalized in Department of Respiratory Medicine of Zhengzhou Second People′s Hospital from January 1, 2014 to December 31, 2018. Patients who met the inclusion criteria were divided into 3 groups: doxofylline group, terbutaline group, and combination of doxofylline and terbutaline group (combination group). All patients in the 3 groups were given conventional treatments and symptomatic treatments. Doxofylline 300 mg once daily was given by an IV infusion and terbutaline 2 ml (5 mg) thrice daily was given by atomized inhalation for 7-14 days. Adverse reactions in the 3 groups were compared. The dosage of doxofylline in patients with adverse reactions of grade 1 was adjusted to 250 mg once daily, 200 mg once daily for patients with adverse reactions of grade 2, and doxofylline was stopped in patients with adverse reactions of more than grade 3. The blood concentration of doxofylline, the proportion of the patients whose adverse reactions were alleviated or disappeared, the length of hospital stay, and the efficiency of treatment before and after dose adjustment of doxofylline in patients in the doxofylline group and the combination group were compared.Results:A total of 6 582 patients were entered in the study. Of them, 1 438 patients were in the doxofylline group, including 793 males and 645 females with age of (61±11) years; 2 217 patients were in the terbutaline group, including 1 281 males and 936 females with age of (60±15) years; 2 927 patients were in the combination group, including 1 644 males and 1 283 females with age of (63±12) years. The differences in gender, age distribution, basic disease, combined disease, and combination medication among the 3 groups were not statistically significant ( P>0.05). The overall incidences of adverse reactions in the 3 groups were 13.1% (189/1 438), 8.9% (197/2 217), and 21.2% (620/2 927), respectively, which was higher in the combination group than that in the doxofylline group ( χ 2=41.271, P<0.001) and the terbutaline group ( χ 2=142.766, P<0.001) and higher in the doxofylline group than that in the terbutaline group ( χ 2=16.738, P<0.001). The incidences of tremor and headache in the combination group were higher than those in the other 2 groups( P<0.001), the incidence of hyperglycemia was higher than that in the doxofylline group( P=0.003), the incidence of insomnia was higher than that in the terbutaline group( P<0.001), the incidence of tachycardia was higher than that in the terbutaline group( P<0.001), the incidence of nausea was lower than that in the doxofylline group( P<0.001) and higher than that in the terbutaline group( P<0.001), the incidence of mood disorders was higher than that in terbutaline group ( P=0.017). No adverse reactions of more than grade 3 occurred in the 3 groups, the difference in proportions of patients with adverse reactions of grade 1 and grade 2 was not statistically significant( χ 2=1.097, P=0.578). The difference in blood concentration of doxofylline in patients with adverse reactions between the combination group and the doxofylline group was not statistically significant before dose adjustment ( P>0.05), but all decreased after dose adjustment (all P<0.001) and the blood concentration of doxofylline in the combination group was lower than that in the doxofyllin group [(8.38±2.19) μg/ml) vs. (10.64±2.55) μg/ml, P<0.001]; the proportion of patients whose adverse reactions were alleviated or disappeared in the combination group was higher than that in the doxofylline group [40.81% (253/620) vs. 30.16% (57/189), P=0.008], the hospitalization time was shorter than that in the doxofylline group [(10±2) d vs. (15±3) d, P<0.001], the treatment efficiency was higher than that in the doxofylline group [531 (85.65%) vs. 136 (71.96%), P<0.001]. Conclusion:When doxofylline injection is combined with terbutaline solution for nebulizationor, the blood concentration of doxofylline can be controlled at (8.38±2.19) μg/ml by monitoring the blood concentration of doxofylline, which can not only improve the treatment efficacy, but also improve the medication safety.
