title: Evaluation of initial dofetilide dosing recommendation based on actual body weight in overweight and obese patients.
abstract: OBJECTIVE
  The dofetilide label recommends using actual body weight (ABW) to calculate the Cockcroft-Gault creatinine clearance (CrCl) for the determination of the initial dose; however, few studies have attempted to evaluate this dosing recommendation in overweight and obese patients. We evaluated whether the current dofetilide dosing recommendation based on ABW is appropriate in overweight and obese patients.
  
  
  METHODS
  This is a retrospective cohort study conducted at two large academic medical centres in the United States on overweight and obese patients (body mass index ≥ 25 kg/m(2)) who were newly started on dofetilide based on ABW. Patients were categorized into (i) the different-dose group if their CrCl calculated based on the ideal body weight (IBW) resulted in a lower initial dofetilide dose compared with ABW-based CrCl and (ii) the same-dose group if they would have the same initial dose based on IBW and ABW. The primary outcome was dofetilide dose reduction or discontinuation due to prolongation of the corrected QT interval during the first 3 days of dofetilide therapy. Multivariable logistic regression analysis was performed to identify factors predicting the risk of primary outcome.
  
  
  CONCLUSIONS
  Of the 132 patients included in the study, 29 (22·0%) were in the different-dose group and 40 (30·3%) had the primary outcome. The per cent of patients with the primary outcome was not statistically significantly different between the different-dose and same-dose groups (37·9% vs. 28·2%; P = 0·31). Diabetes mellitus was a significant predictor for the primary outcome (odds ratio 2·54; 95% confidence interval 1·05-6·15).
  
  
  CONCLUSIONS
  Our study provides the evidence on the safety of the current dofetilide dosing recommendation in overweight and obese populations in clinical practice. Current ABW-based dofetilide dosing is reasonable in overweight and obese patients.
authors.affiliation: Department of Pharmacy Practice, Loma Linda University School of Pharmacy, Loma Linda, CA, USA.
authors.forename: D X
authors.identifier: http://orcid.org/0000-0002-6083-837X
authors.initials: DX
authors.lastname: Cao
authors.affiliation: Department of Pharmacy Practice, Loma Linda University School of Pharmacy, Loma Linda, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kohatsu
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Eng
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Mei
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Dinh
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Mok
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Moreau
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Le
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shin
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000503:physiopathology*; D050177:Overweight / Q000503:physiopathology*; D010627:Phenethylamines / Q000008:administration & dosage*; D012189:Retrospective Studies; D013449:Sulfonamides / Q000008:administration & dosage*
chemical_list: D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide
keywords: dofetilide; initial dosing, obesity; safety