What is the half-life of apixaban?

Half-Life of Apixaban

The half-life of apixaban is approximately 12 hours following oral administration in patients with normal renal function. 1, 2

Pharmacokinetic Details

• Standard half-life: Apixaban has an apparent half-life of approximately 12 hours after oral administration 1, 2
• Alternative reported range: Some sources cite the terminal plasma half-life as 8-14 hours in healthy subjects 1
• Time to peak concentration: Maximum plasma concentrations (Cmax) occur 3-4 hours after oral administration 2, 3
• Time to steady state: Apixaban reaches steady-state anticoagulant effects within 3 days of twice-daily dosing 1, 2

Critical Factors That Modify Half-Life

Renal Impairment

The half-life of apixaban is significantly prolonged in patients with renal dysfunction, which is clinically important since approximately 27% of total drug clearance occurs via renal excretion 1, 2:

• Normal renal function (CrCl ≥80 mL/min): ~12 hours 1
• Mild impairment (CrCl 50-79 mL/min): ~15 hours 1
• Moderate impairment (CrCl 30-49 mL/min): ~18 hours 1
• Severe impairment (CrCl 15-29 mL/min): ~27 hours 1
• End-stage renal disease (CrCl <15 mL/min): ~30 hours off dialysis 1
• ESRD on hemodialysis: Apixaban 17 hours off dialysis 1

Hemodialysis Considerations

• Dialysis clearance is minimal: Only approximately 4% of apixaban is removed during a 4-hour hemodialysis session 4
• Dialysis clearance rate: Approximately 18 mL/min 2
• Post-dialysis exposure: Systemic exposure is 36% higher when apixaban is administered immediately after hemodialysis completion compared to patients with normal renal function 2

Genetic Polymorphisms

• Multiple pathway impairment: Patients with concurrent genetic polymorphisms affecting CYP3A5, ABCG2, and ABCB1 can have substantially prolonged elimination half-lives (up to ~31 hours reported in one case) 5
• Clinical significance: Combined genetic variants can impair multiple apixaban elimination pathways, leading to excessive drug exposure even with standard dosing 5

Clinical Implications for Timing

Perioperative Planning

• Drug washout period: Based on the 12-hour half-life, apixaban should be discontinued 2-4 days before high-risk procedures depending on renal function 1:
  • CrCl >80 mL/min: 2 days
  • CrCl 50-80 mL/min: 2 days
  • CrCl 30-50 mL/min: 2 days
  • CrCl 15-30 mL/min: 2 days (though use is not recommended)

Reversal Considerations

• Rapid offset: Due to the relatively short 12-hour half-life, temporary cessation may be sufficient for non-life-threatening bleeding 1
• Activated charcoal window: Most effective if administered within 3 hours of the last dose, as peak plasma concentration occurs at 3-4 hours 1

Common Pitfalls

• Assuming uniform half-life: The 12-hour half-life applies to patients with normal renal function; always assess creatinine clearance as the half-life can more than double in severe renal impairment 1
• Overestimating dialysis removal: Hemodialysis removes only 4% of apixaban, so it is not an effective method for drug removal in overdose situations (unlike dabigatran) 1, 2, 4
• Ignoring genetic factors: In rare cases, patients with multiple genetic polymorphisms affecting drug metabolism and transport can have markedly prolonged half-lives despite normal renal function 5
• Unexpected prolongation: Case reports document apixaban remaining detectable for >10 days after the last dose in elderly patients with chronic kidney disease, which can delay necessary surgical interventions 6