title: Dosing of dabigatran etexilate in relation to renal function and drug interactions at a tertiary hospital.
abstract: BACKGROUND
  Plasma concentrations of the anticoagulant dabigatran are correlated with clinical outcomes, and are affected by renal function, intestinal P-glycoprotein (P-gp) activity and stomach acidity.
  
  
  OBJECTIVE
  To determine the adherence to dabigatran etexilate renal dosing guidelines, the frequency of co-prescription of potentially interacting drugs in patients on dabigatran, and how these related to dabigatran dosing.
  
  
  METHODS
  A retrospective chart review of 204 patients discharged from a tertiary hospital on dabigatran etexilate over a 12-month period. Creatinine clearance, using the Cockcroft-Gault equation, was used as the surrogate of renal function in the 86 patients where this was calculable.
  
  
  RESULTS
  Prescribed dabigatran etexilate dose rates in relation to creatinine clearance and the manufacturer's guidelines were classified as 'standard', 'low' and 'high' in 47% (40/86), 49% (42/86) and 5% (4/86) of patients respectively. Co-prescribed drugs that potentially interact with dabigatran etexilate were present in 75% (154/204) of patients and included strong P-gp inhibitors (16%, 32/204), proton-pump inhibitors (46%, 94/204) and anti-platelet drugs (47%, 95/204). Co-prescription of strong P-gp inhibitors was associated with the prescription of 'low' dose rates relative to renal function (P = 0.025).
  
  
  CONCLUSIONS
  Few patients were dosed excessively in relation to creatinine clearance. Around 50% was prescribed with 'low' dose rates in relation to creatinine clearance, which because of the association with co-prescription of strong P-gp inhibitors may be clinically appropriate. Most patients were co-prescribed with drugs that potentially interact with dabigatran etexilate.
authors.affiliation: Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand. paulc@cdhb.health.nz
authors.forename: P K L
authors.initials: PK
authors.lastname: Chin
authors.forename: J W A
authors.initials: JW
authors.lastname: Vella-Brincat
authors.forename: S L
authors.initials: SL
authors.lastname: Walker
authors.forename: M L
authors.initials: ML
authors.lastname: Barclay
authors.forename: E J
authors.initials: EJ
authors.lastname: Begg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000378:metabolism; D000069604:Dabigatran; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage* / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage* / Q000378:metabolism; D012189:Retrospective Studies; D062606:Tertiary Care Centers
chemical_list: D001562:Benzimidazoles; D011355:Prodrugs; D011725:Pyridines; D000069604:Dabigatran
keywords: P-glycoprotein; clearance; dabigatran; glomerular filtration rate; kidney clearance