Liver function monitoring: a prospective nested case-control study of Salvia miltiorrhiza polyphenol injection

Abstract

instructions for Salvia miltiorrhiza polyphenol injections indicate abnormal liver function as an occasional adverse reaction, but the incidence of this adverse drug reaction (ADR) has increased in recent years. We assessed S. miltiorrhiza polyphenol ADRs by performing a nested case-control study(NCCS) and meta-analysis. In the NCCS, 2633 patients receiving this treatment in the First Affiliated Hospital of Bengbu Medical College were enrolled. Logistic regression models found that in 58 (2.2%) patients experiencing abnormal liver function, the risk for liver dysfunction was associated with sulfa drug allergy (OR = 7.874, 95%CI (1.280, 48.447), P = 0.026), payment methods (OR = 0.106, 95%CI (0.012, 0.934), P = 0.043), duration of administration (OR = 0.922, 95%CI (0.862, 0.986), P = 0.017), cefathiamidine (OR = 0.441, 95%CI (0.216, 0.900), P = 0.025), human serum albumin (OR = 1.958, 95%CI (1.011, 3.789), P = 0.046), Dazhu Rhodiola injection (OR = 2.599, 95%CI (1.112, 6.070), p = 0.027), or reduced glutathione (OR = 0.394, 95%CI (0.188, 0.826), P = 0.014). Meta-analysis of reports on S. miltiorrhiza polyphenol ADRs in controlled trials and other observational studies included 676 patients, of which 17 (2.17%; 95%CI (0.0105, 0.0358)) presented with liver dysfunction; associated ADR risk factors included co-administration of other drugs. Our NCCS and meta-analysis had similar ADR incidence rates, which were higher than the rate in the drug instructions. This study provides guidance for assessing liver dysfunction risks associated with S. miltiorrhiza polyphenol injections.An injectable formulation of Salvia miltiorrhiza polyphenols prepared as a multi-effect antioxidant freeze-dried powder was jointly developed by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Shanghai Green Valley (Group) Co., Ltd. Its main active component is magnesium lithospermate B (Fig. 1), a salvianolic acid B salt extracted from the traditional Chinese medicinal herb Danshen (S. miltiorrhiza). The injectable formulation, which exerts anti-arrhythmic and antioxidant effects and protects the endothelium, is used to treat coronary heart disease, angina pectoris, and ischemic stroke 1-7 .The abnormal liver function indicated in the Salvia miltiorrhiza polyphenols injection instructions is an occasional adverse reaction. It is clinically manifested mainly as elevated glutamine-pyruvate transaminase activity, which can be improved after drug withdrawal. This is based on early research conducted under normal and reasonable use. The probability of occurrence of occasional adverse reactions ranges from 0.1% to 1% according to the Council for International Organizations of Medical Sciences (CIOMS) 8 . However, with the increasing use of S. miltiorrhiza polyphenol injections, especially when used in combination with other drugs, the clinical manifestation and severity of liver dysfunction have far exceeded the ones known during their launch 9 . Case reports, randomized placebo-controlled clinical studies, and literature ana...

Safety, tolerance, and pharmacokinetics of salvianolic acid B in healthy Chinese volunteers: A randomized, double-blind, placebo-controlled phase 1 clinical trial

“…Sal B is methylated by the liver to produce active metabolites, which may cause potential hepatotoxicity. Therefore, serum biochemical indicators should be concerned ( Jia et al, 2010 ; Cheng et al, 2020 ). Blood alanine aminotransferase, glutamyl transpeptidase, aspartate aminotransferase, alkaline phosphatase, and/or bilirubin increased in 11 volunteers treated with Sal B, while only aspartate aminotransferase increased in the placebo group.…”

Pseudo-allergic reactions induced by Chinese medicine injections: a review

“…When these particles enter blood vessels, they can cause a series of adverse reactions to Chinese herbal injections. In addition, simultaneous and rapid infusion of multiple drugs can make the vascular wall in a state of high-pressure stimulation, aggravating the damage to the vascular wall and causing adverse reactions [ 32 ]. Therefore, TCMIs should not be compatible with other medications and should be used separately whenever possible.…”