Postmarketing safety evaluation: depside salt injection made from Danshen(Radix Salviae Miltiorrhizae)

OBJECTIVE: To systematically examine the postmarketing safety of depside salt injection made from Danshen(Radix Salviae Miltiorrhizae),identifythe potential risk factors, and ensure its clinical safety.METHODS: We examined a comprehensive series of studies on the production process, quality standards, pharmacology, population pharmacokinetics, and safety evaluation of depside salt injection made from Danshen(Radix Salviae Miltiorrhizae). Data from Ⅰ-Ⅳ clinical drug trials, hospital information systems(HIS), and spontaneous reporting systems(SRS) were also analyzed.RESULTS: The effective components of salvianolic acid salt content reached almost 100%, and the magnesium lithospermate B content reached morethan 80%. The median lethal dose(LD50) calculated by the Bliss method was 1.49 g/kg, with 95%confidence intervals of 1.29-1.72 g/kg. Long-term tests on Beagle dogs indicated that doses of less than 80 mg/kg were safe and doses of 320 mg/kg were toxic. Adverse drug reactions(ADRs) included digestive disorders; drug-induced erythrocyte deformation in lung, liver, spleen, kidney, bone marrow, intestinal mucosa, lymph nodes, and other tissues; megakaryocytes in lung, liver, and spleen resulting from mild hemolysis; and mild hyperplasia in bone marrow hematopoietic tissue. Other studies indicated no irritative effect of the injection on local tissues and blood vessels, and no allergic reactions, erythrocyte coagulation, or hemolysis. SRS data showed that the most common ADRs were headache, head distention, dizziness, facial flushing, skin itching, thrombocytopenia, and the reversibility of elevated Aspartate transaminase. HIS data indicated no damage to renal function from using depside salt injection made from Danshen(Radix Salviae Miltiorrhizae) at a dosage higher than the recommended dose.CONCLUSION: This study analyzes the clinical characteristics of ADRs from depside salt injection made from Danshen(Radix Salviae Miltiorrhizae),and discusses the factors influencing such reactions. It provides scientific reference and recommendations for clinically safe medication of the Danshen injection.

Postmarketing studies on safety of Dengfeng~ shenmai injection

OBJECTIVE: To systematically research the postmarketing safety of Dengfeng shenmai injection, identify potential risk factors, and ensure its clinical safety. METHODS: We investigated a comprehensive series of studies on the production process, quality standards, pharmacology, postmarketing clinical studies, and safety evaluation of Shenmai injection, including literature analysis of adverse drug reaction(ADR) case analysis and systematic review. Data from the hospital information system(HIS) and spontaneous reporting system(SRS) were also analyzed. RESULTS: The approximate dosage leading to death in dogs is 45.0-67.5 g raw drug/kg and the toxic reactions are restlessness, skin irritation, salivation, and vomiting. The results of chronic toxicity tests in mice and dogs, and the other tests such as 6-month toxicity, drug safety, genetic toxicity, and reproductive toxicity of rats and dogs, were positive or qualified. Patient ADR history and ADR family history were closely associated with itching based on the data analysis from SRS. There was no damage to renal function from Shenmai injection use at a dosage and a treatment course outside the recommended dosage and treatment course as specified based on data analysis from HIS. The most common ADR from Shenmai injection are difficulty breathing, facial flushing, nausea, vomiting, chest tightness, skin itching, rash, and back pain. CONCLUSION: This study includes complete information on Shenmai injection ADR incidence rate. We found that Shenmai injection is safe and this study can provide clinical, research, and production institutions with an objective, reliable, and scientific basis for use of Shenmai injection.

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.