What is the recommended dosing regimen for Xarelto (rivaroxaban) in the treatment of pulmonary embolism (PE)?

Xarelto (Rivaroxaban) Dosing for Pulmonary Embolism

For acute PE treatment, start rivaroxaban 15 mg twice daily for the first 21 days, then transition to 20 mg once daily for continued anticoagulation. 1, 2, 3

Initial Treatment Phase (Days 1-21)

• Rivaroxaban 15 mg orally twice daily for exactly 3 weeks (21 days) is the established initial dosing regimen 1, 2
• No parenteral anticoagulation (heparin or enoxaparin) is required before starting rivaroxaban, making it a true single-drug regimen 2
• Take with food to optimize absorption 3
• This dosing was validated in the EINSTEIN-PE trial (n=4,832), which demonstrated non-inferiority to enoxaparin/warfarin with a recurrent VTE rate of 2.1% vs 1.8% (HR 1.12; 95% CI 0.75-1.68) 1, 4

Maintenance Phase (Day 22 Onward)

• Rivaroxaban 20 mg once daily starting on day 22 1, 2, 3
• Continue for a minimum of 3 months total treatment duration 2
• Can be taken with or without food during maintenance phase 3
• The once-daily maintenance dosing improves adherence compared to twice-daily regimens 2

FDA-Approved Starter Pack

• A 30-day starter pack is available containing 42 tablets of 15 mg and 9 tablets of 20 mg, designed to cover the initial 21 days of twice-daily dosing plus 9 days of once-daily maintenance 3

Safety Profile

• Major bleeding occurred in only 1.1% of rivaroxaban patients vs 2.2% with standard therapy (HR 0.49; 95% CI 0.31-0.79) in EINSTEIN-PE 1, 4
• The principal safety outcome of major or clinically relevant non-major bleeding showed similar rates between rivaroxaban (10.3%) and standard therapy (11.4%) 1, 4
• No routine coagulation monitoring is required, unlike warfarin 2

Extended Treatment Beyond 6 Months

• For patients requiring extended anticoagulation after completing at least 6 months of full-dose therapy, rivaroxaban can be reduced to 10 mg once daily 2
• This reduced dose is appropriate only for unprovoked PE requiring indefinite anticoagulation 2
• The dose reduction should never occur before completing 6 months of standard-dose treatment 2

Renal Dosing Adjustments

• For creatinine clearance 15-30 mL/min: reduce to 15 mg once daily (skip the twice-daily phase) 2
• Rivaroxaban is contraindicated in patients with CrCl <15 mL/min 3
• Renal function should be assessed before initiating therapy 2

Administration Considerations

• Patients who cannot swallow tablets whole can crush rivaroxaban and mix with applesauce, followed by food 3
• For patients with NG or gastric feeding tubes, crush the tablet and mix with water before administering 3
• The 15 mg and 20 mg doses must be taken with food to ensure adequate absorption, while the 10 mg dose can be taken without food 3

Clinical Advantages Over Standard Therapy

• Shorter hospital stays: Rivaroxaban treatment resulted in a mean reduction of 1.7 days in hospitalization compared to enoxaparin/warfarin in North American patients 2
• In one academic center study, patients discharged on rivaroxaban had significantly shorter hospital stays (median 6 vs 8 days, p=0.0005) compared to those on VKA 5
• No need for bridging therapy or overlapping parenteral anticoagulation 2
• Fixed dosing eliminates the need for INR monitoring and dose adjustments 2

Common Pitfalls to Avoid

• Do not skip the initial 21-day twice-daily phase - the 15 mg twice daily dosing for 3 weeks is critical for adequate initial anticoagulation 1, 2
• Do not forget to take with food during the initial and maintenance phases when using 15 mg or 20 mg doses - absorption is significantly reduced without food 3
• Do not reduce to 10 mg daily prematurely - this lower dose is only for extended prophylaxis after at least 6 months of standard treatment 2
• Do not use in severe renal impairment (CrCl <15 mL/min) as rivaroxaban is contraindicated 3

Special Populations

• Cancer patients: Rivaroxaban has demonstrated effectiveness in cancer-associated PE, with similar or better efficacy compared to LMWH in clinical trials 2
• Low-risk PE patients: Can be considered for outpatient management with rivaroxaban using the standard dosing regimen, as validated in studies using modified Hestia criteria 1
• Heparin-induced thrombocytopenia (HIT): Rivaroxaban at standard PE dosing may be considered as an alternative anticoagulant 2