title: Physical and chemical compatibility of drotrecogin alfa (activated) with 34 drugs during simulated Y-site administration.
abstract: OBJECTIVE
  The physical and chemical compatibility of drotrecogin alfa (activated) (recombinant human activated protein C) during simulated Y-site administration with drugs commonly used to treat patients with severe sepsis was determined.
  
  
  METHODS
  Thirty-four drugs were investigated for visual compatibility with drotrecogin alfa, and included cardiovascular agents, conscious sedative agents, antibiotics, blood products, and other supportive care drugs. The physical and chemical compatibility of drotrecogin alfa with these drugs was determined using a well-established experimental model to simulate Y-site administration. Drotrecogin alfa (activated) was prepared as 100- and 1000-microg/mL solutions in 0.9% sodium chloride injection. All other drugs were prepared at maximum concentrations commonly administered in the clinical setting. Visual compatibility was assessed by visual inspection (observations of haziness, color change, or precipitate formation) and pH measurement at 0, 30, 60, and 240 minutes after mixing.
  
  
  RESULTS
  Of the 34 test drugs, 8 were defined as visually compatible with drotrecogin alfa; these drugs were further assessed for chemical compatibility with drotrecogin alfa. The protein content, potency, and purity of drotrecogin alfa were determined at 0, 60, and 240 minutes after Y-site mixing as indicators of chemical compatibility. Six drugs (ceftriaxone, cisatracurium, fluconazole, nitroglycerin, potassium chloride, and vasopressin) were determined to be chemically compatible with drotrecogin alfa; two drugs (cyclosporine and ticarcillin-clavulanate) were chemically incompatible with drotrecogin alfa after Y-site mixing.
  
  
  CONCLUSIONS
  Ceftriaxone, cisatracurium, fluconazole, nitroglycerin, potassium chloride, and vasopressin were physically and chemically compatible with drotrecogin alfa in a simulated Y-site infusion; 28 other drugs were incompatible with drotrecogin alfa.
authors.affiliation: College of Pharmacy, University of Minnesota (UM), Minneapolis, USA.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Mann
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Demmon
authors.forename: Debra A
authors.initials: DA
authors.lastname: Boelk
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Payne
authors.forename: Mark B
authors.initials: MB
authors.lastname: Effron
authors.forename: Natarajan
authors.initials: N
authors.lastname: Rajagopalan
authors.forename: Mark D
authors.initials: MD
authors.lastname: Williams
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Beck
authors.forename: Ganapathy
authors.initials: G
authors.lastname: Gopalrathnam
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004344:Drug Incompatibility; D006801:Humans; D007262:Infusions, Intravenous; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000145:classification; D019999:Pharmaceutical Solutions / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011486:Protein C / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics*; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics*
chemical_list: D004364:Pharmaceutical Preparations; D019999:Pharmaceutical Solutions; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated