Concomitant Medication Use With Xiyanping Injection and the Risk of Suspected Allergic Reactions: A Nested Case-Control Study Based on China's National Medical Insurance Database

Xunliang Tong; Xiaochen Zhu; Chunping Wang; Yifan Zhou; Yingying Yan; Siyan Zhan; He Zhu; Sheng Han; Yinchu Cheng

doi:10.3389/fphar.2022.883407

Concomitant Medication Use With Xiyanping Injection and the Risk of Suspected Allergic Reactions: A Nested Case-Control Study Based on China's National Medical Insurance Database

Front Pharmacol. 2022 Jun 21:13:883407. doi: 10.3389/fphar.2022.883407. eCollection 2022.

Authors

Xunliang Tong¹, Xiaochen Zhu^{2

3}, Chunping Wang^{2

3}, Yifan Zhou⁴, Yingying Yan⁵, Siyan Zhan⁶, He Zhu^{2

3}, Sheng Han^{2

3}, Yinchu Cheng⁵

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, National Center of Gerontology, Beijing Hospital, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
² International Research Center for Medicinal Administration, Peking University, Beijing, China.
³ Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Science, Peking University, Beijing, China.
⁴ Chongqing Bashu Secondary School, Chongqing, China.
⁵ Department of Pharmacy, Peking University Third Hospital, Beijing, China.
⁶ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.

Abstract

Introduction: Xiyanping injection (XYP), a type of Traditional Chinese Medicine, is widely used and often applied in combination with other medications in treating bronchitis, tonsillitis, and bacillary dysentery in China. In recent years, an elevated risk of allergic reactions has been observed following XYP, but whether concomitant medication use contributes to this risk is still unknown. Objective: This study aims to investigate the association between the concomitant use of XYP and the 25 most frequently co-applied medications with suspected allergic reactions for China's patients receiving XYP. Methods: A nested case-control study was conducted using the sampling data from 2015 China's Urban Employees Basic Medical Insurance and Urban Residents Basic Medical Insurance database. Four anti-allergic marker drugs were used to evaluate suspected allergic reactions. Univariate analyses and multivariable conditional logistic regression were conducted, and results were reported as odds ratios (ORs) with a 95% confidence interval (CI). Sensitivity analyses were performed on the expanded sample by including those prescribed with anti-allergic marker drugs on the same day as XYP and then stopped XYP on the next day. Results: Out of 57,612 participants with XYP prescription, we obtained 949 matched case-control pairs. Multivariable conditional logistic regression revealed that seven concomitant medications including gentamicin [OR = 4.29; 95% CI (2.52, 7.30)], cefoperazone-sulbactam [OR = 4.26; 95% CI (1.40, 13.01)], lidocaine [OR = 2.76; 95% CI (1.79, 4.25)], aminophylline [OR = 1.73; 95% CI (1.05, 2.85)], ribavirin [OR = 1.54; 95% CI (1.13, 2.10)], potassium chloride [OR = 1.45; 95% CI (1.10, 1.91)], and vitamin C [OR = 1.32; 95% CI (1.03, 1.70)] were associated with increased risk, while cefathiamidine [OR = 0.29; 95% CI (0.16, 0.51)] was associated with reduced risk. Sensitivity analysis on 2,438 matched pairs revealed similar findings. Conclusion: Increased risks for suspected allergic reactions were found for the concomitant use of XYP with seven medications. Our data suggest that gentamicin, cefoperazone-sulbactam, lidocaine, and ribavirin should be applied with precautions for patients receiving XYP, and further studies on drug interactions and allergy mechanisms are warranted.

Keywords: Xiyanping injection; allergic reaction; concomitant medication; drug safety; nested case–control study.