title: Factors associated with optimized tacrolimus dosing in hematopoietic stem cell transplantation.
abstract: OBJECTIVE
  The primary objective was to analyze the initial tacrolimus concentrations achieved in allogeneic hematopoietic stem cell transplantation patients using the institutional dosing strategy of 1 mg IV daily initiated on day +5. The secondary objectives were to ascertain the tacrolimus dose, days of therapy, and dose changes necessary to achieve a therapeutic concentration, and to identify patient-specific factors that influence therapeutic dose. The relationships between the number of pre-therapeutic days and incidence of graft-versus-host disease and graft failure were delineated.
  
  
  METHODS
  A retrospective chart review included adult allogeneic hematopoietic stem cell patients who received tacrolimus for graft-versus-host disease prophylaxis in 2012. Descriptive statistics, linear and logistic regression, and graphical analyses were utilized.
  
  
  RESULTS
  Ninety-nine patients met the inclusion criteria. The first concentration was subtherapeutic (<10 ng/ml) in 97 patients (98%). The median number of days of tacrolimus needed to achieve a therapeutic trough was 10 with a median of two dose changes. The median therapeutic dose was 1.6 mg IV daily. Approximately 75% of patients became therapeutic on ≤ 2 mg IV tacrolimus daily. No relationship was found between therapeutic dose and any patient-specific factor tested, including weight. No relationship was found between the number of days of therapy required to achieve a therapeutic trough and incidence of graft-versus-host disease or graft failure.
  
  
  CONCLUSIONS
  An initial flat tacrolimus dose of 1 mg IV daily is a suboptimal approach to achieve therapeutic levels at this institution. A dose of 1.6 mg or 2 mg IV daily is a reasonable alternative to the current institutional practice.
authors: Department of Pharmacy, University of Kentucky HealthCare, Lexington, USA arbu223@uky.edu.
authors: Allison R
authors: AR
authors: Butts
authors: Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, USA.
authors: Victoria T
authors: VT
authors: Brown
authors: Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, USA.
authors: Lauren D
authors: LD
authors: McBride
authors: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, USA.
authors: Javier
authors: J
authors: Bolaños-Meade
authors: Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, USA.
authors: Amy W
authors: AW
authors: Bryk
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: Tacrolimus; allogeneic stem cell transplantation; graft failure; graft-versus-host disease; immunosuppression