What is the recommended apixaban dosing regimen for acute deep‑vein thrombosis, including standard and reduced doses based on age ≥ 80 years, body weight ≤ 60 kg, or impaired renal function, and contraindications?

Apixaban Dosing for Acute Deep Vein Thrombosis

For acute DVT, initiate apixaban 10 mg orally twice daily for 7 days, then reduce to 5 mg twice daily for at least 3–6 months; no dose reduction is needed during acute treatment regardless of age, weight, or renal function unless creatinine clearance falls below 15 mL/min. 1, 2

Initial Loading Phase (Days 1–7)

• Administer apixaban 10 mg orally twice daily for the first 7 days to achieve rapid therapeutic anticoagulation without any preceding parenteral heparin or low-molecular-weight heparin bridge. 1, 2
• Start the first dose immediately upon confirmation of DVT diagnosis. 1
• This loading regimen was validated in the AMPLIFY trial (5,395 patients), demonstrating non-inferiority to enoxaparin/warfarin for preventing recurrent VTE (2.3% vs 2.7%; RR 0.84,95% CI 0.60–1.18) with significantly lower major bleeding (0.6% vs 1.8%; RR 0.31,95% CI 0.17–0.55; P < 0.001). 1, 2

Maintenance Phase (After Day 7)

• Switch to apixaban 5 mg orally twice daily after completing the 7-day loading period and continue for a minimum of 3–6 months depending on whether the DVT was provoked or unprovoked. 1, 2
• This maintenance dose applies to all patients during the primary treatment phase—no dose reduction is indicated even in elderly patients (≥80 years), low body weight (≤60 kg), or elevated serum creatinine (≥133 μmol/L or 1.5 mg/dL). 2

Critical Distinction: Atrial Fibrillation Dose-Reduction Criteria Do NOT Apply to DVT

• The dose-reduction criteria used for atrial fibrillation (two of three: age ≥80 years, weight ≤60 kg, serum creatinine ≥133 μmol/L) are not applicable to acute DVT treatment. 3, 2
• During the initial and maintenance phases of DVT therapy, continue the full treatment dose (10 mg BID then 5 mg BID) regardless of these patient characteristics. 2

Extended Secondary Prevention (Beyond 6 Months)

• For patients requiring anticoagulation beyond 6 months for secondary VTE prevention, reduce to apixaban 2.5 mg orally twice daily. 3, 2
• This lower dose maintains efficacy for preventing recurrent VTE while reducing bleeding risk during extended therapy. 3, 2
• The American Society of Hematology suggests either standard-dose (5 mg BID) or lower-dose (2.5 mg BID) DOAC for extended prophylaxis, with the choice depending on individual bleeding vs thrombosis risk. 3

Absolute Contraindications

• Creatinine clearance < 15 mL/min (calculated by Cockcroft-Gault equation): apixaban is contraindicated. 1, 2
• Severe hepatic impairment (transaminases > 2× upper limit of normal or total bilirubin > 1.5× ULN): apixaban is contraindicated. 1, 2
• Active pathological bleeding, intracranial vascular malformations, or recent high-risk bleeding events. 4

Renal Function Considerations

• Calculate creatinine clearance using the Cockcroft-Gault formula before initiating therapy. 1, 4
• Apixaban has only 27% renal elimination (lower than other DOACs), with a half-life extending to approximately 17 hours in elderly patients with impaired renal function. 1, 4
• Use caution when CrCl is 15–30 mL/min, as such patients were excluded from pivotal trials. 2
• Reassess renal function periodically during treatment, especially in elderly patients or after surgical procedures. 1

Baseline Laboratory Testing

• Obtain complete blood count with platelet count, comprehensive metabolic panel (including serum creatinine), and hepatic function panel (AST, ALT, total bilirubin) before starting apixaban. 1
• Record baseline PT/INR and aPTT for documentation only; routine INR monitoring is not required or recommended during apixaban therapy. 1

Monitoring During Treatment

Laboratory Monitoring

• Check hemoglobin/hematocrit every 2–3 days during the first 14 days if hospitalized, then at least every 2 weeks or as clinically indicated. 1
• Reassess renal function periodically, particularly in high-risk populations. 1
• Do not routinely monitor INR, anti-factor Xa activity, or D-dimer in patients on therapeutic apixaban. 1

Clinical Monitoring

• Actively assess for bleeding signs: bruising, hematuria, melena, hemoptysis, or neurological changes. 1, 4
• Monitor for recurrent VTE symptoms: new leg swelling, chest pain, or dyspnea. 1
• Observe for compartment syndrome if hematoma develops, even when painless. 1

Special Populations

Cancer-Associated DVT

• Apixaban is a viable option for cancer-associated DVT, with recent data demonstrating non-inferiority to dalteparin. 2
• Use the same dosing regimen (10 mg BID × 7 days, then 5 mg BID) for cancer patients. 2

Elderly Patients

• Patients ≥75 years have increased risk of gastrointestinal and intracranial bleeding with DOACs compared to younger patients. 4
• However, do not reduce the dose during acute DVT treatment based on age alone; maintain the full treatment regimen. 2
• Enhanced clinical monitoring for bleeding is warranted. 4

Critical Pitfalls to Avoid

• Do NOT use the 2.5 mg twice-daily dose for acute DVT treatment, even in elderly, low-weight patients with elevated creatinine; this dose is reserved exclusively for extended secondary prevention after 6 months of full-dose therapy or for atrial fibrillation. 1, 2, 4
• Do NOT bridge with parenteral anticoagulation (heparin or LMWH) before starting apixaban; direct initiation with the 10 mg BID loading dose is recommended. 1, 2
• Do NOT apply atrial fibrillation dose-reduction criteria to acute DVT treatment; these are separate indications with different dosing algorithms. 2, 4
• Do NOT restart apixaban immediately after high-risk bleeding or major surgery; wait 24–72 hours to ensure adequate hemostasis. 1
• Do NOT combine with other anticoagulants, antiplatelets (except in specific ACS scenarios), NSAIDs, SNRIs, or SSRIs without careful risk-benefit assessment due to increased bleeding risk. 4
• Do NOT use with combined P-glycoprotein and strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir). 4