Apixaban Dosing for Chronic Pulmonary Embolism Therapy
For chronic pulmonary embolism therapy, apixaban should be administered at 10 mg twice daily for 7 days, followed by 5 mg twice daily for at least 3 months, with consideration for extended therapy based on risk factors.
Initial Treatment Phase
The recommended dosing regimen for apixaban (Eliquis) in the treatment of pulmonary embolism follows a two-phase approach:
Initial phase (first 7 days):
- 10 mg taken orally twice daily
Maintenance phase (after first 7 days):
- 5 mg taken orally twice daily
This dosing regimen is supported by high-quality evidence from the AMPLIFY trial, which demonstrated that apixaban was noninferior to conventional therapy (enoxaparin/warfarin) in preventing recurrent VTE and was associated with significantly less major bleeding (0.6% vs 1.8%) 1.
Duration of Treatment
The duration of anticoagulation depends on the clinical scenario:
- Provoked PE (temporary risk factors): 3 months
- Unprovoked PE or persistent risk factors: Extended therapy (>3 months)
- Recurrent PE: Indefinite treatment
For extended treatment beyond the initial treatment period, the recommended dose is:
- 2.5 mg twice daily after at least 6 months of treatment at the standard dose 2
Special Considerations
Renal Function
- Apixaban should be avoided in patients with severe renal impairment (CrCl <15 mL/min) 3
- Patients with CrCl <25 mL/min were excluded from clinical trials with apixaban 3
Hepatic Function
- Apixaban should be avoided in patients with hepatic impairment (transaminases >2 times upper limit of normal or total bilirubin >1.5 times upper limit of normal) 3
Drug Interactions
- For patients receiving apixaban doses of 5 mg or 10 mg twice daily, reduce the dose by 50% when coadministered with drugs that are combined P-glycoprotein (P-gp) and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) 2
- In patients already taking 2.5 mg twice daily, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors 2
Cancer-Associated Thrombosis
For patients with active cancer and PE:
- The standard apixaban dosing regimen (10 mg twice daily for 7 days, followed by 5 mg twice daily) has been shown to be noninferior to dalteparin for treatment of cancer-associated VTE without increased risk of major bleeding 4
- For extended treatment beyond 6 months in cancer patients, a reduced dose of 2.5 mg twice daily has been shown to be noninferior to the full 5 mg twice daily dose with lower bleeding risk 5
Clinical Efficacy and Safety
Apixaban has demonstrated favorable outcomes in multiple clinical trials:
- In the AMPLIFY trial, apixaban showed a 2.3% rate of recurrent VTE compared to 2.7% with conventional therapy (relative risk 0.84) 1
- Major bleeding was significantly reduced with apixaban (0.6%) compared to conventional therapy (1.8%) (relative risk 0.31) 1
- Real-world studies have confirmed these findings, showing 27-39% lower risk of major bleeding and 25-39% lower risk of recurrent VTE compared to warfarin across various time points and patient subgroups 6
Temporary Interruption for Procedures
If apixaban needs to be temporarily discontinued:
- Stop apixaban at least 48 hours prior to elective surgery or invasive procedures with moderate/high bleeding risk
- Stop apixaban at least 24 hours prior to procedures with low bleeding risk
- Resume apixaban as soon as adequate hemostasis has been established 2
Missed Dose Management
If a dose is missed:
- Take the missed dose as soon as possible on the same day
- Resume twice-daily administration schedule
- Do not double the dose to make up for a missed dose 2
Conclusion
Apixaban offers an effective and convenient option for PE treatment with a favorable safety profile compared to traditional anticoagulation. The fixed-dose regimen without need for routine monitoring simplifies management while providing effective protection against recurrent VTE with lower bleeding risk.