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 exa...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.展开更多
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...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.展开更多
基金National Science and Technology Major Projects for"Major New Drugs Innovation and Development":Study on Key Technologies of Postmarketing Evaluation forChinese Medicine(No.2009ZX09502-030)
文摘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.
基金Supported by National Science and Technology Major Projects for "Major New Drugs Innovation and Development":Study on Key Technologies of Postmarketing Evaluation for Chinese Medicine(No.2009ZX09502-030)
文摘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.
