Can rivaroxaban (Xarelto) be used in gastrointestinal (GI) diseases?

Rivaroxaban Use in Gastrointestinal Diseases

Rivaroxaban can be used in patients with gastrointestinal diseases if there is no coagulopathy associated with liver disease, but caution is warranted due to increased risk of gastrointestinal bleeding compared to warfarin, particularly in elderly patients. 1

Pharmacokinetics and Metabolism in GI Disease

• Rivaroxaban is a direct competitive inhibitor of factor Xa with rapid absorption and a half-life of 7-11 hours 1, 2
• Two-thirds of rivaroxaban is metabolized in the liver, but it can be used in patients with liver disease as long as there is no coagulopathy 1
• Only about one-third of active rivaroxaban is cleared by the kidneys with no accumulation when creatinine clearance (CrCl) is above 15 mL/min 1
• Rivaroxaban is rapidly absorbed in the upper gastrointestinal tract, and bariatric surgery of the upper GI tract does not significantly impair its absorption 3

Dosing Considerations in GI Disease

• Standard dosing is 20 mg once daily with food for most indications 2
• Dose reduction to 15 mg once daily is recommended for patients with CrCl between 15-30 mL/min 1, 2
• Rivaroxaban is not recommended when CrCl is ≤15 mL/min 1, 2
• Taking rivaroxaban with the evening meal is important for optimal anticoagulation effect 2

Risk of GI Bleeding with Rivaroxaban

• Lower gastrointestinal bleeding occurs more frequently in elderly patients with rivaroxaban compared to warfarin 1
• In the ROCKET AF trial, there was a significantly higher rate of major or non-major clinical GI bleeding in rivaroxaban versus warfarin-treated patients (3.61 vs. 2.60 events/100 patient-years) 4
• However, severe GI bleeding rates and fatal GI bleeding events were similar between rivaroxaban and warfarin, with fatal events being rare 4

Risk Factors for GI Bleeding with Rivaroxaban

• The first 40 days of taking rivaroxaban is associated with higher risk of GI bleeding (OR = 2.8) 5
• Concomitant use of dual antiplatelet agents significantly increases risk of GI bleeding (OR = 7.4) 5
• Prior history of GI bleeding is a major risk factor (OR = 15.5) 5
• Baseline anemia, history of GI bleeding, and long-term aspirin use are independently associated with increased risk of GI bleeding 4
• Age ≥75 years is associated with increased risk of GI bleeding 1

Special Considerations for GI Diseases

• Patients with gastric or gastroesophageal tumors are at increased risk for hemorrhage with direct oral anticoagulants including rivaroxaban; LMWH may be preferred in these patients 6
• Rivaroxaban should be used with caution in patients with a history of gastrointestinal disorders due to the increased risk of bleeding 1
• Protease inhibitors (used in HIV treatment) should not be co-administered with rivaroxaban due to risk of GI bleeding 7

Monitoring and Management

• Unlike warfarin, routine coagulation monitoring is not required for rivaroxaban 6
• If bleeding occurs, temporarily discontinue rivaroxaban and provide supportive care 6
• For major bleeding, consider reversal agents such as prothrombin complex concentrates 6
• The effect of rivaroxaban on coagulation tests can be reversed by prothrombin complex concentrate (50 IU/kg of 4-factor concentrate) 1
• Anti-factor Xa assays with specific rivaroxaban calibrators can be used to determine drug concentration if needed 1

Precautions

• Avoid rivaroxaban in patients with active bleeding 1
• Avoid combination with antiplatelets, thrombolytics, NSAIDs, SNRIs, or SSRIs when possible 1
• Consider proton pump inhibitors in patients at high risk of GI bleeding 1
• Rivaroxaban should be used with caution in patients with a history of gastrointestinal disorders 1