title: Absence of clinically relevant interactions between rivaroxaban--an oral, direct Factor Xa inhibitor--and digoxin or atorvastatin in healthy subjects.
abstract: OBJECTIVE
  To investigate potential interactions between rivaroxaban, an oral direct Factor Xa inhibitor approved for the management of thromboembolic disorders, and digoxin or atorvastatin.
  
  
  METHODS
  Two randomized, phase 1 clinical trials were undertaken in healthy men to assess pharmacokinetic  and pharmacodynamic interactions between rivaroxaban and digoxin or atorvastatin, and the safety of these drug combinations.
  
  
  RESULTS
  Steady-state rivaroxaban did not affect the pharmacokinetic profile of steady-state digoxin (n = 17). Digoxin did not significantly influence the pharmacokinetic  profile of single-dose rivaroxaban and had minimal effects on rivaroxaban-induced inhibition of Factor Xa activity and prolongation of clotting time. Similarly, steady-state atorvastatin did not affect the pharmacokinetic profile or the pharmacodynamics of rivaroxaban and vice versa  (n = 19). All drugs (alone or in combination) were well tolerated.
  
  
  CONCLUSIONS
  There were no clinically relevant pharmacokinetic or pharmacodynamic interactions between rivaroxaban and digoxin, or between rivaroxaban and atorvastatin, suggesting that rivaroxaban can be coadministered  with either drug. This study also confirmed that rivaroxaban does not interact with substrates for permeability (P)-glycoprotein alone (digoxin) or P-glycoprotein and cytochrome P(450) (CYP)3A4 (atorvastatin).
authors.affiliation: Clinical Pharmacology, Bayer Pharma AG, Wuppertal, Germany. dagmar.kubitza@bayer.com
authors.forename: D
authors.initials: D
authors.lastname: Kubitza
authors.forename: M
authors.initials: M
authors.lastname: Becka
authors.forename: A
authors.initials: A
authors.lastname: Roth
authors.forename: W
authors.initials: W
authors.lastname: Mueck
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000069059:Atorvastatin; D018592:Cross-Over Studies; D004077:Digoxin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006261:Headache / Q000139:chemically induced; D006538:Heptanoic Acids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D011758:Pyrroles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000069552:Rivaroxaban; D012646:Self Administration; D013876:Thiophenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000889:Anti-Arrhythmia Agents; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D006538:Heptanoic Acids; D009025:Morpholines; D011758:Pyrroles; D013876:Thiophenes; D004077:Digoxin; D000069552:Rivaroxaban; D000069059:Atorvastatin