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
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.
