What is the half-life of apixaban (anticoagulant)?

Half-Life of Apixaban

Apixaban has a half-life of approximately 12 hours in patients with normal renal function. 1, 2

Pharmacokinetic Profile of Apixaban

Apixaban is a direct factor Xa inhibitor with the following key pharmacokinetic properties:

• Absorption: Rapidly absorbed with peak plasma concentrations occurring 1-3 hours after oral administration 1
• Bioavailability: Approximately 50% 2, 3
• Protein binding: Highly protein-bound (87%) 2
• Distribution: Volume of distribution approximately 21 liters 2
• Metabolism:
  • 25% hepatically metabolized, primarily via CYP3A4 1
  • Minor metabolism through CYP1A2, 2C8, 2C9, 2C19, and 2J2 1
• Elimination:
  • 27% renal excretion 1, 2
  • 73% biliary and intestinal excretion 2
• Steady state: Reached within 3 days of regular dosing 1

Half-Life Variations Based on Patient Factors

The half-life of apixaban can vary depending on several patient-specific factors:

Renal Function

• Normal renal function: ~12 hours 1, 2
• 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: ~30 hours (off dialysis) 1

Hepatic Function

• Mild impairment (Child-Pugh A): No significant change in half-life 4, 2
• Moderate impairment (Child-Pugh B): Modest impact with AUC increased by 1.09-fold 4
• Severe impairment (Child-Pugh C): Not well studied; apixaban should be avoided 4

Age

• Elderly patients may have slightly prolonged half-life due to decreased renal function 2

Clinical Implications of Apixaban's Half-Life

The 12-hour half-life of apixaban has several important clinical implications:

1. Dosing frequency: Requires twice-daily dosing to maintain therapeutic levels 1

2. Perioperative management:

   • For low bleeding risk procedures: Stop apixaban 24 hours before surgery 1
   • For high bleeding risk procedures: Stop apixaban 48-72 hours before surgery 1

3. Anticoagulant effect persistence: The pharmacodynamic effect of apixaban can be expected to persist for at least 24 hours after the last dose (approximately two half-lives) 2

4. Reversal considerations: In cases of bleeding, the anticoagulant effect may persist for 24 hours or longer after the last dose 2

Common Pitfalls and Caveats

1. Drug interactions: Apixaban is a substrate for P-glycoprotein (P-gp) and CYP3A4. Strong inhibitors of both pathways can significantly increase apixaban levels and effective half-life 1, 2

2. Renal function assessment: Always assess renal function before prescribing apixaban, as decreased renal function prolongs half-life 1

3. Missed doses: Due to the relatively short half-life compared to warfarin (which has a 20-60 hour half-life), missed doses of apixaban can more quickly lead to loss of anticoagulant effect 1, 2

4. Transitioning between anticoagulants: The half-life must be considered when switching between anticoagulants to avoid periods of either insufficient or excessive anticoagulation

5. Laboratory monitoring: Unlike warfarin, routine laboratory monitoring is not required due to predictable pharmacokinetics, but this can make it difficult to assess compliance or anticoagulant effect 2

By understanding apixaban's half-life and its variations based on patient factors, clinicians can optimize dosing strategies, manage perioperative anticoagulation, and address potential bleeding complications more effectively.