What is the half-life of Xarelto (rivaroxaban)?

Half-Life of Rivaroxaban (Xarelto)

The half-life of rivaroxaban (Xarelto) is 5 to 9 hours in healthy adults aged 20 to 45 years, and extends to 11 to 13 hours in older patients. 1, 2

Pharmacokinetic Profile of Rivaroxaban

Rivaroxaban is an orally administered direct factor Xa inhibitor with the following key pharmacokinetic properties:

• Absorption:

  • Rapid absorption with peak plasma concentrations reached in 2-4 hours after oral administration 3
  • High oral bioavailability (80-100%) for the 10 mg tablet regardless of food intake 3
  • For 15 mg and 20 mg tablets, should be taken with food to increase bioavailability 1

• Distribution:

  • Highly protein-bound in plasma (92-95%) 1
  • Considered a low-clearance drug due to high protein binding 1

• Metabolism and Elimination:

  • Dual mode of excretion 3:
    • 66% renal excretion (36% as unchanged drug) 1
    • 28% excreted in feces (7% unchanged) 1
  • Metabolized via oxidative and hydrolytic pathways 1
  • CYP3A4 and CYP2J2 are the primary enzymes responsible for oxidative metabolism 1
  • Also a substrate for P-glycoprotein (P-gp) transporter 1

Age-Related Differences in Half-Life

The half-life of rivaroxaban varies based on age:

• Young healthy adults (20-45 years): 5-9 hours 1, 2
• Elderly patients (>75 years): 11-13 hours 1, 3

This extended half-life in older patients is clinically significant and should be considered when prescribing rivaroxaban to elderly patients, especially those with renal dysfunction.

Clinical Implications of Rivaroxaban's Half-Life

• Steady-state concentrations are typically achieved within 2-3 days of regular dosing 1
• The relatively short half-life compared to some other anticoagulants means:
  • Rapid onset of action (anticoagulant effect within 2-4 hours) 3
  • Relatively quick offset of action after discontinuation
  • When discontinuing rivaroxaban, consider transitioning to another anticoagulant to prevent thrombotic events 4

Special Population Considerations

• Renal impairment:

  • Rivaroxaban should be used with caution in patients with moderate renal impairment (CrCl 30-50 mL/min) 1, 4
  • Avoid in patients with severe renal impairment (CrCl <30 mL/min) 1, 4
  • Renal function affects drug clearance and can extend the half-life 1

• Hepatic impairment:

  • Not recommended in patients with moderate to severe hepatic impairment (Child-Pugh B and C) 1
  • Hepatic function impacts metabolism and can affect half-life 1

• Body weight:

  • Use with caution in patients weighing less than 50 kg 1, 4
  • Pharmacokinetics may be altered in extreme body weights 1

Drug Interactions Affecting Half-Life

• Strong inhibitors of both CYP3A4 and P-gp (such as azole antimycotics and HIV protease inhibitors) can significantly increase rivaroxaban exposure and potentially extend its half-life 1, 4
• Strong inducers of CYP3A4 and P-gp may decrease rivaroxaban exposure and potentially shorten its effective half-life 1

Understanding rivaroxaban's half-life is essential for proper dosing, managing perioperative periods, and addressing potential bleeding complications. Unlike warfarin, routine coagulation monitoring is not required for rivaroxaban therapy 4.