Chinese medicine has a history of thousands of years in China. More than 9,000 Chinese medicine preparations have been approved for use in China (Zhu et al., 2010). Traditional Chinese medicine (TCM) injections have a history of 80 years and are still widely used today (Jing-Yao et al., 2016). Compared with other dosage forms, such as tablets, pills, and oral liquid, they have the advantage of rapid onset (Wang et al., 2017). In 2017, China approved the sale of 134 kinds of TCM injections from 224 manufacturers (Li et al., 2018). Sales of TCM injections have reached >30 billion RMB and account for one-third of all TCM sales in hospitals (Li et al., 2018).

However, with the application of TCM injections, an increasing number of adverse drug reactions (ADRs) have been reported (Li et al., 2019). Such findings have raised concerns about the safety and potential toxicity of currently used TCM injections. In response to this situation, the National Food and Drug Administration (CFDA) has adopted a series of measures. For example, although many kinds of TCM injections exist, only 10 were included in the National Essential Drugs List (2018)1 ¹ . Since 2017, the National Medical Insurance Catalogue has restricted the use of Shuanghuanglian, Reduning, Qingkailing, Ciwujia, Xuesaitong, and many more commonly used TCM injections ^{2 , 3 , 4} . They can only be used in secondary and above medical institutions and are restricted to certain populations and diseases. Given such management measures, in 2020, about 74,800 ADRs were caused by TCM injections, which was a decrease of 14.5% from 87,500 in 2019. The proportion of injection in the ADRs of TCM also decreased significantly. ^{5 , 6} However, as a result of inadequate supervision and insufficient patient awareness, many primary medical institutions still use TCM injections. Most of these medical institutions are located in the suburbs and rural areas of China, and effective response is difficult if ADRs occur. Nevertheless, safety studies on TCM injections in primary medical institutions remain sparse.

Spontaneous reporting system (SRS) has the advantage of covering a large number of patients and a wide range of drugs, and nearly 16.87 million ADR reports have been collected from 1999 to 2020 (Guo et al., 2015). Different from the current research, this article started from the perspective of management by focusing on a variety of TCM injections in primary medical institutions about safety by analyzing China’s provincial SRS database.

Statistics show that the reports of TCM injections reported by the SRS have shown a downward trend in the past 5 years, and the proportion of primary medical institutions is declining yearly. We believe that this decline is due to the introduction of an increasing number of restrictive measures for TCM injections in recent years, especially the strict management and restriction of the use of TCM injections at primary medical institutions (Xiao et al., 2013).

However, given the lack of clinical evidence or experience on the safety and effectiveness of TCM injections, and most TCM injections have been approved for sale many years ago, by today’s standards, there is insufficient evidence of safety and effectiveness (Liu et al., 2016). The results of this study showed that 15.9% of patients had ADRs after using TCM injections, which was higher than the average level of 9.1% in Henan Province in our research database.

Data from this study further suggested that SADR patients have more SADRs, such as dyspnea, chest distress, cardiopalm, and anaphylactic shock, are common in this population. Studies have shown that these adverse reaction symptoms cause poor prognosis (Bouzillé et al., 2018; Li et al., 2019).

Compared with non-primary medical institutions, the SADRs faced by primary medical institutions are more serious because of the lack of professionals or equipment and infrequent related training, so the risk of using Chinese medicine injections in primary medical institutions is high (Faria et al., 2014). Thus, primary medical institutions still cannot relax the supervision of TCM injections.

In our cases, the risk of SADRs among the elderly (>60) injected with TCM at primary medical institutions significantly increased. This result was speculated to be correlated with the patients’ own constitution, metabolism, and decline of organs (Wang et al., 2018). The safety of elderly medication must be given close attention (Qing et al., 2019).

Using TCM injections outside the essential medicine list in primary medical institutions could also lead to poor results. Interestingly, the use of injections in the essential medicine list has a low probability of SADR, thereby illustrating the importance of popularizing essential medicines. Season was also a factor that should be paid attention. Previous studies on ADRs and seasons reported that the proportions of SADRs in autumn and winter increase significantly because patients are highly sensitive to drug reactions during this time. Weather, flu, and seasonal allergies also yielded similar results (Chabanon et al., 2021; Deb et al., 2021). However, the reasons related to TCM injections need to be further studied.

Shuanghuanglian and Ciwujia injection have low risk of SADRs when used in primary medical institutions. However, they can also cause allergic shock, so China also restricts their use. Safflower and danshen injections are more risky when used in primary medical institutions. Safflower injection can cause allergic shock, and danshen injection is a potential vascular toxic drug in high dosage, so it should not be used far beyond its recommended dosage for clinical treatment (Sun et al., 2013; Wang et al., 2015). Given that Chinese medicine is considered only a complementary treatment for the control of hypertension and protection of target organs (Wu and Dong, 2015), if patients want to stabilize their condition for a long time, then systematic treatment in a comprehensive medical institution is necessary. Chemotherapy is also not suitable for the use of TCM injections, because the patients need to be treated in professional medical institutions; given their poor physique and health, injection at primary medical institutions will only increase their risk of SADRs (Zhang et al., 2014).

In summary, the innovation of this study was the analysis of the harm of using TCM injection in different levels of medical institutions and proposal of recommendations to avoid serious consequences. Nevertheless, this study had potential limitations. First, the effect estimated in the study was based on the data only in Henan Province. Although the data were considerable, the external validity of the conclusion still needs to be improved. Second, some recorded ADR information was incomplete, and some indicators had a few missing values, which may cause a certain degree of bias. Finally, given the insufficient content of the original database, this study did not specifically analyze the relationship between ADRs and drugs used.

In general, the number of reported cases of TCM injections is declining, which is important to achieve safe medication. However, the proportion of SADRs in primary medical institutions has increased, and the regression results also showed that the level of drug administration institutions was a risk factor. Although the government has introduced many regulatory policies, banning primary medical institutions from using TCM injections in the near future was unrealistic. Therefore, this study demonstrated that populations (>60), drugs (safflower and danshen), and reason for medication (chemotherapy and hypertension) need to be supervised, and recommendations for the use of essential drugs must be made. These measures can help in reducing the incidence of SADRs.

In the future, restriction of TCM injections should be continued at the macro policy level, and various essential drug lists must be promoted; at the micro level, intervention is necessary in specific populations, specific diseases, and specific drugs to effectively prevent SADR occurrences in primary medical institutions. This study also proved that SADR was likely to occur when using TCM injections in primary medical institutions, and specific factors only occurred at primary medical institutions. This work reflects the necessity of the state to introduce regulatory policies and further points out the direction for policy pertinence.