title: Post-Marketing Safety Surveillance of the Salvia Miltiorrhiza Depside Salt for Infusion: A Real World Study.
abstract: BACKGROUND
  Salvia Miltiorrhiza Depside Salt for Infusion (SMDS) is made of a group of highly purified listed drugs. However, its safety data is still reported limitedly. Compared with the clinical trials, its safety in the real world setting is barely assessed.
  
  
  OBJECTIVE
  To investigate the safety issues, including adverse events (AEs), adverse events related to SMDS (ADEs), and adverse drug reactions (ADRs) of the SMDS in the real world clinical practice.
  
  
  METHODS
  This is a prospective, multicenter, pharmacist-led, cohort study in the real world setting. Consecutive patients prescribed with SMDS were all included in 36 sites. Pharmacists were well trained to standardized collect the patients information, including demographics, medical history, prescribing patterns of SMDS, combined medications, adverse events, laboratory investigations, outcomes of the treatment when discharge, and interventions by pharmacists. Adverse events and adverse drug reactions were collected in details. Multivariate possion regression analysis was applied to identify risk factors associated with ADEs using the significance level (α) 0.05. ClinicalTrials.gov Identifier: NCT01872520.
  
  
  RESULTS
  Thirty six hospitals were participated in the study and 30180 consecutive inpatients were included. The median age was 62 (interquartile range [IQR], 50-73) years, and male was 17384 (57.60%) among the 30180 patients. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. There were 9 kinds of new ADEs which were not on the approved label found in the present study. According to the multivariate analysis, male (RR = 1.381, P = 0.009, 95%CI [1.085~1.759]), more concomitant medications (RR = 1.049, P<0.001, 95%CI [1.041~1.057]), longer duration of SMDS therapy (RR = 1.027, P<0.001, 95%CI [1.013~1.041]), higher drug concentration (RR = 1.003, P = 0.014, 95%CI [1.001~1.006]), and resolvent unapproved (RR = 1.900, P = 0.002, 95%CI [1.260~2.866]) were the independent risk factors of the ADEs. Moreover, following the approved indication (RR = 0.655, P<0.001, 95%CI [0.532~0.807]) was associated with lower incidence of ADEs.
  
  
  CONCLUSIONS
  SMDS was well tolerated in the general population. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. Several risk factors of its ADEs have been identified. It is recommended to follow the instructions when prescribing and administrating SMDS in the real world clinical practice.
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, 49 North Garden Rd., Haidian District Beijing, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Yan
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, 49 North Garden Rd., Haidian District Beijing, China.
authors.forename: Yi-Heng
authors.initials: YH
authors.lastname: Yang
authors.affiliation: School of Public Health, Peking University Health Center, 38 Xueyuan Rd., Haidian District, Beijing, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Wang
authors.affiliation: School of Public Health, Peking University Health Center, 38 Xueyuan Rd., Haidian District, Beijing, China.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Pan
authors.affiliation: School of Public Health, Peking University Health Center, 38 Xueyuan Rd., Haidian District, Beijing, China.
authors.forename: Si-Yan
authors.initials: SY
authors.lastname: Zhan
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, 49 North Garden Rd., Haidian District Beijing, China.|Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Center, 38 Xueyuan Rd., Haidian District, Beijing, China.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Sun
authors.affiliation: State Administration of Traditional Chinese Medicine of the People's Republic of China, 55 Xingfu Yicun, Chaoyang District, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, 49 North Garden Rd., Haidian District Beijing, China.
authors.forename: Suo-Di
authors.initials: SD
authors.lastname: Zhai
mesh_terms: D000368:Aged; D002681:China; D015331:Cohort Studies; D053630:Depsides / Q000009:adverse effects* / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000503:physiopathology; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008516:Medicine, Chinese Traditional / Q000009:adverse effects*; D008875:Middle Aged; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D017673:Sodium Chloride, Dietary / Q000627:therapeutic use
chemical_list: D053630:Depsides; D017673:Sodium Chloride, Dietary