What is the plasma half‑life of apixaban in adults, and is it prolonged in the elderly or in patients with impaired renal or hepatic function?

Half-Life of Apixaban

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

Standard Half-Life in Adults

• Apixaban has an apparent elimination half-life of approximately 12 hours following oral dosing, which allows for twice-daily administration. 1, 2
• The drug reaches peak plasma concentration at 3-4 hours after oral administration and achieves steady-state within 3 days of twice-daily dosing. 1, 2
• The half-life is reported as 7-8 hours in some perioperative guidelines, though the more commonly cited value is 12 hours based on pharmacokinetic studies. 1

Half-Life in Elderly Patients

• The half-life of apixaban does not appear to be significantly prolonged in elderly patients compared to younger adults, unlike rivaroxaban which extends from 5-9 hours in young patients to 11-13 hours in older patients. 1
• However, elderly patients may experience prolonged drug exposure due to age-related decline in renal function rather than age itself. 1

Half-Life with Renal Impairment

• Renal impairment can substantially prolong apixaban's half-life because approximately 27% of total clearance occurs via renal excretion. 1, 2
• In patients with moderate renal impairment (CrCl 30-50 mL/min), the half-life extends, requiring longer preoperative interruption periods (3-4 days vs 2-3 days for normal function). 1
• A case report documented an elimination half-life of approximately 31 hours in a patient with moderate renal impairment (CrCl 40 mL/min) combined with genetic polymorphisms affecting drug clearance pathways. 3
• Another case with impaired renal function (creatinine 1.81 mg/dL) demonstrated an apparent elimination half-life of 14 hours during massive overdose. 4

Half-Life with Hepatic Impairment

• Apixaban is primarily metabolized via the liver (CYP3A4-dependent), but specific data on half-life prolongation in hepatic impairment are limited. 1
• The drug should be avoided in patients with hepatic impairment (transaminases >2× upper limit of normal or total bilirubin >1.5× upper limit of normal), though precise half-life data in this population were not established in clinical trials. 1

Clinical Implications

• The 12-hour half-life means that apixaban effects dissipate within 24-48 hours (2-4 half-lives) after discontinuation in patients with normal renal function. 1
• For elective surgery with high bleeding risk, the last dose should be given 3 days before surgery (skip 4 doses) to allow 4-5 half-lives to elapse, ensuring minimal residual anticoagulant effect. 1
• Detectable apixaban levels can persist for >10 days in patients with significantly impaired clearance, as documented in a case report of an elderly patient with chronic kidney disease. 5

Common Pitfalls

• Do not assume the half-life remains constant at 12 hours in all patients—always assess renal function (CrCl) before estimating drug clearance time. 1, 3
• The 27% renal clearance makes apixaban more favorable than dabigatran (80% renal) or rivaroxaban (66% renal) in patients with renal impairment, but prolonged half-life still occurs with moderate-to-severe kidney disease. 1, 6
• Genetic polymorphisms in CYP3A5, ABCG2, and ABCB1 can substantially impair apixaban elimination, leading to unexpectedly prolonged half-life even with only moderate renal impairment. 3