Establishment of safety evidence for Xingxue~ Shuxuening injection

OBJECTIVE: To systematically investigate the safety of Xingxue~ Shuxuening injection(SXN) in preand post-marketing, and to ensure clinical drug safety.METHODS: Strict quality control in raw herb selection and production processes was adopted and pharmacology research on SXN was performed by the drug manufacturing company, Heilongjiang ZBD Pharmaceutical Co., Ltd. We systematically reviewed the safety literature of Xingxue~ SXN. Adverse drug reaction(ADR) data of the drug, extracted from Spontaneous Reporting System(SRS), and clinical characters based on 20 hospital information systems(HIS) in China, were analyzed. Large-scale prospective safety monitoring and Risk Minimization Action Plans(Risk MAPs) of Xingxue~SXN were carried out.RESULTS: The quality of SXN was stable and controllable when it was produced. Drug toxicology studies found no effect on rabbits with hemolytic or condensed, local stimulation and muscle stimulation, and no allergic reactions in guinea pigs. The ADRs of Xingxue~ SXN were dizziness, phlebitis,and vomiting based on SRS data. The injection did not conform to instructions in clinical practice when we analyzed HIS database, and patient’s abnormal blood urea nitrogen levels may be related to the drug, when analyzed using the propensity score method. A nested case-control study was designed and performed to analyze the influencing factors of suspected allergic reactions to SXN. The study showed that patients with an allergy history were more prone to allergic reactions(P<0.001),and some medicine combinations could cause allergic reactions.CONCLUSION: These studies have established a body of evidence on Xingxue~ SXN safety, and provide a good model for Chinese medicine injection for clinical safety. The Xingxue~ SXN production process and toxicology research indicate the safety of the injection. However, the use of the injection is not consistent with instructed clinical practice.Xingxue~ SXN causes ADRs perhaps from inappropriate usage or its pharmacological action. This injection needs better Risk MAPs to ensure its clinical safety.