What is the half-life of factor Xa (factor Xa inhibitors) in adults with a history of thrombotic events or at risk of such events?

Half-Life of Factor Xa Inhibitors

The half-life of factor Xa inhibitors ranges from 5-14 hours depending on the specific agent and patient age, with rivaroxaban having a half-life of 5-13 hours, apixaban 9-14 hours, and edoxaban 10-14 hours. 1

Specific Agent Half-Lives

Rivaroxaban

• Terminal elimination half-life: 5-9 hours in healthy young subjects (aged 20-45 years) 2, 3
• Extended half-life: 11-13 hours in elderly subjects 2, 4, 3
• Half-life range across populations: 7-11 hours for young adults and 11-13 hours for elderly 4
• The FDA label specifies the terminal elimination half-life as 5-9 hours in healthy subjects aged 20-45 years 2

Apixaban

• Half-life: 9-14 hours 1
• Approximate half-life: 12 hours 5
• Time to peak levels occurs at 3 hours post-administration 1

Edoxaban

• Half-life: 10-14 hours 1
• Time to peak levels occurs at 1-2 hours, the fastest among factor Xa inhibitors 1

Clinical Implications of Half-Life

Timing Considerations for Procedures

• For rivaroxaban and apixaban in major elective surgery or neuraxial blockade: discontinue 3 days before surgery in patients with renal dysfunction 1
• For rivaroxaban and apixaban in other surgical contexts: discontinue 24-48 hours before surgery 1
• The relatively short half-lives (compared to warfarin) allow for more predictable offset of anticoagulant effect 1

Renal Impairment Impact

• All factor Xa inhibitors have prolonged half-lives in renal dysfunction because of renal-dependent clearance 1
• Rivaroxaban: 66% hepatic metabolism, 33% renal excretion 1
• Apixaban: 27% renal excretion 1
• Edoxaban: 50% renal excretion 1
• The dependence on renal function for clearance means higher blood levels and longer half-lives occur in patients with renal dysfunction 1

Reversal Agent Timing

• An indwelling epidural catheter should not be removed before at least 2 half-lives have elapsed (approximately 10-18 hours for rivaroxaban, 18-28 hours for apixaban) 2
• Andexanet alfa produces anti-factor Xa activity reduction that persists for the duration of infusion, followed by subsequent increase in anti-factor Xa activity 4 hours after discontinuation 1
• The onset of reversal with andexanet alfa is 2 minutes, with a terminal half-life of approximately 6 hours 1

Dosing Frequency Rationale

• The half-life profiles support once-daily dosing for rivaroxaban (20 mg) and edoxaban (60 mg), and twice-daily dosing for apixaban (5 mg) and dabigatran (150 mg) 1
• Rivaroxaban's half-life of 5-13 hours allows for once-daily dosing with sustained anticoagulant effect 1, 4

Comparison with Other Anticoagulants

Dabigatran (Direct Thrombin Inhibitor)

• Half-life: 12-17 hours 1
• Extended range: 14-17 hours 5
• Significantly longer than factor Xa inhibitors, supporting twice-daily dosing 1

Warfarin

• Factor Xa inhibitors have much shorter half-lives than warfarin, providing faster onset and offset of anticoagulant effect 1
• This shorter half-life eliminates the need for bridging therapy in most situations and allows more predictable perioperative management 1

Key Clinical Pitfalls

• Do not assume the half-life remains constant in elderly patients or those with renal impairment—expect prolongation 1, 2, 4
• The half-life determines when factor Xa activity returns to baseline: rivaroxaban's factor Xa activities do not return to normal until after 24 hours even with the 5 mg dose 1
• Monitoring anticoagulation effect using PT, INR, aPTT, or anti-factor Xa activity is not recommended for dose adjustment 2
• In emergency bleeding situations with factor Xa inhibitors, the relatively short half-lives mean that supportive care alone may be sufficient if the last dose was >12-24 hours prior, depending on renal function 1