title: Administration of voriconazole in patients with renal dysfunction.
abstract: BACKGROUND
  The intravenous use of voriconazole requires coadministration with sulphobutylether-β-cyclodextrin, which may accumulate in patients with impaired renal function.
  
  
  METHODS
  All adult patients treated with the same formulation of voriconazole for a minimum of 3 consecutive days were included. Renal function was assessed based on the creatinine level and the calculated creatinine clearance (CrCl). Change in renal function was calculated on days 3, 7, and end of treatment (EOT) and was defined based on the RIFLE criteria.
  
  
  RESULTS
  Among 166 patients in whom baseline renal function was assessed, 42 (25.3%) had a CrCl <50 mL/min and received intravenous voriconazole, 77 (46.4%) had a CrCl ≥50 mL/min and received intravenous voriconazole, and 47 (28.3%) had a CrCl <50 mL/min and were treated with oral voriconazole. Renal function changed on days 3, 7, and EOT in 19 (11.4%), 14 (8.4%), and 28 (16.9%) patients, respectively. Multivariate analyses identified significant predictors of renal dysfunction: (1) day 3, hematologic malignancy (odds ratio [OR], 5.09, P = .01), fluconazole use within 30 days prior to voriconazole (OR, 6.21; P = .008), coadministration of penicillins (OR, 6.12; P = .03), and immunosuppressants (OR, 7.00; P = .002); (2) day 7, baseline liver impairment (OR, 5.30; P value = .004); (3) EOT, administration of penicillins (OR, 2.39; P = .04).
  
  
  CONCLUSIONS
  Voriconazole route of administration and baseline renal function were not predictors of worsening renal dysfunction on days 3, 7, and EOT. Underlying disease, baseline liver impairment, and concomitant administration of other drugs (eg, penicillins, fluoroquinolones, immunosuppressants) were the strongest predictors of renal dysfunction.
authors.affiliation: Transplant and Oncology Infectious Disease Program, Division of Infectious Diseases, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA. dneofyt1@jhmi.edu
authors.forename: Dionissios
authors.initials: D
authors.lastname: Neofytos
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Lombardi
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Shields
authors.forename: Darin
authors.initials: D
authors.lastname: Ostrander
authors.forename: Lindsay
authors.initials: L
authors.lastname: Warren
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Carol B
authors.initials: CB
authors.lastname: Thompson
authors.forename: Kieren A
authors.initials: KA
authors.lastname: Marr
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects*; D051437:Renal Insufficiency / Q000139:chemically induced*; D012189:Retrospective Studies; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects*; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D003404:Creatinine; D065819:Voriconazole