How to switch from rivaroxaban (Xarelto) to Low Molecular Weight Heparin (LMWH)?

From the Guidelines

To switch from rivaroxaban to low molecular weight heparin (LMWH), stop rivaroxaban and start LMWH 24 hours after the last rivaroxaban dose, as this timing ensures minimal overlap between anticoagulants while maintaining therapeutic anticoagulation coverage, according to the most recent and highest quality study 1. When switching from rivaroxaban to LMWH, it is essential to consider the patient's renal function, as rivaroxaban clearance is reduced in patients with renal impairment. For patients with normal renal function, the recommended timing of 24 hours is appropriate due to rivaroxaban's half-life of 5-9 hours in healthy adults. However, for patients with renal impairment, consider waiting longer (up to 36 hours) to avoid excessive anticoagulation.

Key Considerations for LMWH Dosing

• The LMWH dose depends on the indication and patient factors, such as body weight, renal function, and bleeding risk.
• For venous thromboembolism treatment, enoxaparin is typically given at 1 mg/kg twice daily or 1.5 mg/kg once daily.
• For prophylaxis, lower doses like enoxaparin 40 mg daily are used.
• Monitor for bleeding during the transition, especially in high-risk patients, as the switch from rivaroxaban to LMWH may increase the risk of bleeding, as seen in the SYNERGY trial 1.

Patient-Specific Factors

• Renal function: consider reducing the LMWH dose or using an alternative anticoagulant in patients with severe renal impairment (creatinine clearance <30 mL/min) 1.
• Body weight: adjust the LMWH dose according to the patient's weight, as recommended in the NCCN guidelines 1.
• Bleeding risk: carefully monitor patients with a high risk of bleeding, such as those with gastric or gastroesophageal lesions, as they may require alternative anticoagulation strategies 1.

From the FDA Drug Label

Switching from XARELTO to Anticoagulants other than Warfarin - For adult and pediatric patients currently taking XARELTO and transitioning to an anticoagulant with rapid onset, discontinue XARELTO and give the first dose of the other anticoagulant (oral or parenteral) at the time that the next XARELTO dose would have been taken

• To switch from rivaroxaban (Xarelto) to Low Molecular Weight Heparin (LMWH), discontinue XARELTO and give the first dose of LMWH at the time that the next XARELTO dose would have been taken 2
• This approach ensures a smooth transition between the two anticoagulants with minimal disruption to the patient's treatment regimen.

From the Research

Switching from Rivaroxaban to Low Molecular Weight Heparin (LMWH)

• There are no direct studies on switching from rivaroxaban to LMWH, as most studies focus on switching from LMWH to rivaroxaban 3, 4, 5.
• However, studies on switching from LMWH to rivaroxaban may provide some insight into the reversal process.
• One study found that initiating rivaroxaban approximately 12 or 24 hours after the last LMWH dose provides a simple, well-tolerated transition strategy for thromboprophylaxis in patients undergoing total hip or knee replacement surgery 3.
• Another study found that direct early switching from LMWH to maintenance therapy of rivaroxaban is effective and safe for acute iliofemoral deep vein thrombosis 4.

Measurement of Rivaroxaban Levels using LMWH Calibrated Anti-Xa Assay

• Studies have investigated the use of LMWH calibrated anti-Xa assays to measure rivaroxaban levels in patient samples 6, 7.
• One study found that LMWH anti-Xa activity cut-off values of 0.05 IU/mL and 0.1 IU/mL are suitable for excluding the presence of clinically relevant concentrations of rivaroxaban and apixaban, respectively 6.
• Another study found that LMWH calibrated anti-Xa assay can be used to detect clinically significant apixaban or rivaroxaban levels, with a good correlation between LMWH anti-Xa levels and drug-specific anti-Xa assays 7.

Clinical Implications

• The lack of direct studies on switching from rivaroxaban to LMWH highlights the need for further research in this area.
• However, the available studies suggest that LMWH calibrated anti-Xa assays may be useful in measuring rivaroxaban levels and guiding clinical decisions 6, 7.
• Clinicians should exercise caution when switching between anticoagulants and carefully monitor patients for signs of bleeding or thrombosis 3, 4, 5.