What is the use and dosage of Apixaban (apixaban)?

Apixaban: Use and Dosing Guidelines

Apixaban is primarily indicated for stroke prevention in nonvalvular atrial fibrillation, with a standard dose of 5 mg twice daily for most patients and a reduced dose of 2.5 mg twice daily for patients with at least two high-risk characteristics (age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL). 1

Primary Indications

Apixaban is FDA-approved for:

1. Reduction of stroke and systemic embolism risk in nonvalvular atrial fibrillation 1
2. Prophylaxis of deep vein thrombosis (DVT) following hip or knee replacement surgery 1
3. Treatment of DVT and pulmonary embolism (PE) 1
4. Reduction in the risk of recurrent DVT and PE 1

Dosing Regimens

For Nonvalvular Atrial Fibrillation:

• Standard dose: 5 mg twice daily 1
• Reduced dose: 2.5 mg twice daily for patients with at least two of:
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL 1, 2

For DVT Prophylaxis After Hip/Knee Surgery:

• 2.5 mg twice daily 1
• Initial dose: 12-24 hours after surgery
• Duration: 35 days for hip replacement; 12 days for knee replacement 1

For DVT/PE Treatment:

• 10 mg twice daily for the first 7 days
• Then 5 mg twice daily 1

For DVT/PE Recurrence Prevention:

• 2.5 mg twice daily after at least 6 months of treatment 1

Clinical Evidence Supporting Use

Apixaban has demonstrated superior efficacy compared to warfarin in the ARISTOTLE trial, which showed:

• 21% reduction in stroke or systemic embolism
• 31% reduction in major bleeding
• 11% reduction in all-cause mortality 2

In the AVERROES trial, apixaban was significantly better than aspirin for patients unsuitable for warfarin therapy, with:

• 55% reduction in stroke or systemic embolism
• No significant difference in major bleeding rates 2

Special Dosing Considerations

Renal Impairment

• Patients with severe renal impairment have prolonged drug half-life (approximately 17 hours) compared to normal renal function (12 hours) 3
• For hemodialysis patients, 2.5 mg twice daily is recommended 3

Drug Interactions

• For patients receiving 5 mg or 10 mg twice daily, reduce dose by 50% when co-administered with combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) 1
• For patients already on 2.5 mg twice daily, avoid co-administration with combined P-gp and strong CYP3A4 inhibitors 1

Missed Doses

• Take as soon as possible on the same day
• Resume twice-daily administration
• Do not double the dose to make up for a missed dose 1

Perioperative Management

• Discontinue at least 48 hours prior to elective surgery with moderate/high bleeding risk
• Discontinue at least 24 hours prior to procedures with low bleeding risk
• Bridging anticoagulation is not generally required
• Restart after adequate hemostasis is established 1

Converting Between Anticoagulants

• From warfarin to apixaban: Discontinue warfarin and start apixaban when INR is below 2.0
• From apixaban to warfarin: Discontinue apixaban and begin both parenteral anticoagulant and warfarin at the time of next scheduled apixaban dose 1

Important Warnings

• Premature discontinuation increases thrombotic risk - Consider alternative anticoagulation if stopping for reasons other than bleeding or completion of therapy 1
• Risk of spinal/epidural hematoma - Particularly with neuraxial anesthesia or spinal puncture 1
• No specific reversal agent is available for emergency situations 4

Clinical Pearls

• Apixaban has 27% renal clearance, making it potentially preferable in patients with renal impairment compared to other NOACs with higher renal clearance 3, 5
• Patients with a single dose-reduction criterion (age ≥80, weight ≤60 kg, or creatinine ≥1.5 mg/dL) should still receive the standard 5 mg twice daily dose 6
• Food does not have a clinically meaningful impact on bioavailability 5
• Half-life is approximately 12 hours, requiring twice-daily dosing 5

Apixaban offers significant advantages over warfarin for stroke prevention in atrial fibrillation, with reduced bleeding risk and no need for routine monitoring, making it an excellent choice for most patients requiring anticoagulation.