title: Clinical Application and Pharmacodynamic Monitoring of Apixaban in a Patient with End-Stage Renal Disease Requiring Chronic Hemodialysis.
abstract: Despite prescribing guidance, limited data exist to describe the use of apixaban in patients with end-stage renal disease (ESRD) requiring hemodialysis (HD). Current apixaban dosing recommendations for this patient population are based largely on a single-dose pharmacokinetic study of eight patients. We describe the clinical application and pharmacodynamic monitoring of apixaban in a 62-year-old 156-kg African-American woman with nonvalvular atrial fibrillation and ESRD requiring hemodialysis who developed calciphylaxis while receiving warfarin therapy. Based on a multidisciplinary clinical judgment decision due to concern for drug accumulation after multiple doses in patients with ESRD receiving HD, she was anticoagulated with apixaban 2.5 mg twice/day, as opposed to 5 mg twice/day as recommended by the package insert. Antifactor Xa monitoring was used, and resultant peak and trough apixaban concentrations were above the upper limit of detection for our clinical laboratory (more than 2.00 IU/ml). On day 7 of her hospitalization, the patient developed gastrointestinal bleeding, and apixaban was discontinued; no further clinical signs of bleeding occurred during her subsequent hospitalization course. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between apixaban exposure and the manifestation of gastrointestinal bleeding. The patient ultimately died 44 days after the acute bleeding event; however, coagulation concerns were not implicated in the patient's death. To our knowledge, this is the first case report that describes apixaban use and associated antifactor Xa monitoring in a patient with ESRD receiving HD, and it provides concern for current apixaban dosing recommendations in this patient population. Further pharmacokinetic and clinical data are likely necessary to better characterize apixaban use in these patients to optimize safety and efficacy.
authors.affiliation: Department of Pharmacy, Upstate University Hospital, Syracuse, New York.
authors.forename: Wesley D
authors.initials: WD
authors.lastname: Kufel
authors.affiliation: Department of Medicine, Upstate Medical University, Syracuse, New York.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Zayac
authors.affiliation: Department of Medicine, Upstate Medical University, Syracuse, New York.
authors.forename: David F
authors.initials: DF
authors.lastname: Lehmann
authors.affiliation: Department of Pharmacy, Upstate University Hospital, Syracuse, New York.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Miller
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy; D016903:Drug Monitoring / Q000379:methods; D065427:Factor Xa Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D017809:Fatal Outcome; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D006435:Renal Dialysis / Q000379:methods*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin
keywords: anticoagulation; antifactor Xa monitoring; apixaban; calciphylaxis; end-stage renal disease; hemodialysis; renal dosing; warfarin