What is the recommended dosing of apixaban (apixaban) for a 48-year-old patient with Deep Vein Thrombosis (DVT) and impaired renal function (creatinine clearance of 28)?

Apixaban Dosing for DVT with CrCl 28 mL/min

For this 48-year-old patient with DVT and creatinine clearance of 28 mL/min, use standard-dose apixaban 10 mg twice daily for 7 days, followed by 5 mg twice daily for the initial treatment phase, then consider dose reduction to 2.5 mg twice daily for extended therapy given the severe renal impairment. 1, 2

Initial Treatment Phase (First 3-6 Months)

Standard Dosing Applies Despite Renal Impairment

• Start with apixaban 10 mg orally twice daily for 7 days, then 5 mg twice daily for the remainder of the initial 3-month treatment period 1, 3
• This patient does not meet the dose reduction criteria for initial therapy, which requires at least 2 of 3 criteria: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1
• At age 48 and BMI 28 (approximately 80-85 kg for average height), only the renal criterion is met (CrCl 28 suggests SCr likely >1.5), which is insufficient for dose reduction during acute treatment 1

Renal Function Considerations

• Apixaban is the preferred DOAC in this renal range as it should be avoided only when CrCl <15 mL/min 4, 3
• CrCl of 28 mL/min falls in the "use with caution" zone but is not a contraindication to standard dosing for acute VTE treatment 4
• Recent evidence suggests reduced-dose apixaban (2.5 mg twice daily) may have lower bleeding rates in severe renal disease (CrCl <25 mL/min), but this was studied primarily for extended therapy, not acute treatment 2

Extended-Phase Anticoagulation (After Initial 3-6 Months)

Dose Reduction Recommended

• For extended therapy, use apixaban 2.5 mg twice daily rather than 5 mg twice daily 4, 3
• The CHEST guidelines suggest reduced-dose apixaban (2.5 mg twice daily) over full-dose for extended-phase anticoagulation in all VTE patients 4
• This recommendation is particularly important given the CrCl of 28 mL/min, where bleeding risk is elevated 2

Duration and Monitoring

• Extended anticoagulation is strongly recommended for unprovoked DVT or DVT with persistent risk factors 4
• Extended therapy has no predefined stop date but should be reassessed at least annually 4, 3
• Monitor renal function periodically as further deterioration below CrCl 15 mL/min would contraindicate apixaban 4, 3

Evidence Supporting This Approach

Bleeding Risk in Severe Renal Disease

• A 2022 multicenter study found that standard-dose apixaban (5 mg twice daily) had significantly higher bleeding rates than reduced-dose (2.5 mg twice daily) in patients with CrCl <25 mL/min or on dialysis (14.4% vs 3.8%, p=0.02), with similar VTE recurrence rates 2
• Another 2021 study showed no difference in bleeding between 5 mg and 2.5 mg twice daily in advanced CKD, but the 2.5 mg group had numerically lower bleeding events 5

Clinical Pitfalls to Avoid

• Do not confuse atrial fibrillation dosing with VTE treatment dosing - the initial 10 mg twice daily × 7 days is critical for adequate VTE treatment 1
• Do not use reduced dosing during the acute treatment phase unless the patient meets specific dose reduction criteria (which this patient does not) 1
• Avoid combining with antiplatelet agents, NSAIDs, or other anticoagulants as this substantially increases bleeding risk 4
• Check for drug interactions with strong dual inhibitors of CYP3A4 and P-glycoprotein 1

Practical Algorithm

1. Weeks 1-12: Apixaban 10 mg twice daily × 7 days → 5 mg twice daily
2. After 3-6 months: Reassess for extended therapy indication
3. If extended therapy indicated: Reduce to apixaban 2.5 mg twice daily
4. Monitor: Renal function every 3-6 months; reassess anticoagulation need annually