Rivaroxaban

The most common complication is bleeding; major hemorrhages (eg, intracranial, GI, retinal, epidural hematoma, adrenal bleeding) have been reported. Certain patients are at increased risk of bleeding; risk factors include bacterial endocarditis, congenital or acquired bleeding disorders, vascular retinopathy, thrombocytopenia, recent puncture of large vessels or organ biopsy, stroke, intracerebral surgery, or other neuraxial procedure, severe uncontrolled hypertension, renal impairment, recent major surgery, recent major bleeding (intracranial, GI, intraocular, or pulmonary), concomitant use of drugs that affect hemostasis, and advanced age. Monitor for signs and symptoms of bleeding (weakness, dizziness, unexplained edema). Prompt clinical evaluation is warranted with any unexplained decrease in hemoglobin or blood pressure. No specific antidote for rivaroxaban reversal exists. Rivaroxaban is highly protein-bound, therefore, hemodialysis is ineffective. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban. Depending on the bleeding severity, activated oral charcoal should be considered if ingestion occurred within 1 to 2 hours of presentation. The following alternative options may also be considered depending on specific clinical scenario: 4-factor unactivated prothrombin concentrate (PCC) (eg, Kcentra) or 4-factor activated prothrombin complex concentrate (aPCC) (eg, FEIBA). Some studies and case reports have shown moderate su

As with any oral anticoagulant in the absence of adequate alternative anticoagulation, an increased risk of thrombotic events (including stroke) may occur with premature discontinuation of rivaroxaban. Consider the addition of alternative anticoagulant therapy when discontinuing rivaroxaban for reasons other than pathological bleeding or completion of a course of therapy. An increased rate of stroke was observed during the transition from rivaroxaban to warfarin in clinical trials in atrial fibrillation patients. In a post-hoc analysis of the ROCKET AF trial, patients who temporarily (>3 days) or permanently discontinued anticoagulation, the risk of stroke or non-CNS embolism was similar with rivaroxaban as compared to warfarin (Patel 2013). In patients with non-valvular atrial fibrillation who had an acute ischemic stroke while receiving a DOAC (eg, rivaroxaban), guidelines generally support withholding oral anticoagulation until 4 to 14 days after the onset of neurological symptoms (time frame may vary with shorter times for transient ischemic attack or small, non-disabling stroke and longer times for moderate-to-severe stroke) (AHA/ASA [Kernan 2014]; AHA/ASA [Powers 2018]). Disease-related concerns:

Avoid use in patients with moderate to severe hepatic impairment (Child-Pugh classes B and C) or in patients with any hepatic disease associated with coagulopathy.

Use with caution in patients with moderate renal impairment (CrCl 30 to 50 mL/minute) when used for postoperative thromboprophylaxis, including patients receiving concomitant drug therapy that may increase rivaroxaban systemic exposure and those with deteriorating renal function. Monitor for any signs or symptoms of blood loss. Discontinue use in patients who develop acute renal failure. Use is not recommended in patients with ESRD requiring hemodialysis (Chan 2016). Avoid use in patients with CrCl • Valvular disease: Safety and efficacy have not been established in patients with prosthetic heart valves or significant rheumatic heart disease (eg, mitral stenosis); use is not recommended. Non-valvular atrial fibrillation is defined as atrial fibrillation that occurs in the absence of rheumatic mitral valve disease, mitral valve repair, or prosthetic heart valve (AHA/ACC/HRS [January 2014]). Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Use with caution in the elderly. Elderly patients exhibit higher rivaroxaban concentrations compared to younger patients due primarily to reduced clearance. Overall, efficacy of rivaroxaban in the elderly (age ≥65 years) was similar to that of patients Dosage form specific issues:

May contains lactose; use is not recommended in patients with lactose or galactose intolerance (eg, Lapp lactase deficiency, glucose-galactose malabsorption). Other warnings/precautions:

Rivaroxaban is not recommended as an alternative to unfractionated heparin in the treatment of acute pulmonary embolism in hemodynamically unstable patients or patients requiring thrombolysis or pulmonary embolectomy.

Spinal or epidural hematomas may occur with neuraxial anesthesia (epidural or spinal anesthesia) or spinal puncture in patients who are anticoagulated; may result in long-term or permanent paralysis. The risk of spinal/epidural hematoma is increased with the use of indwelling epidural catheters, concomitant administration of other drugs that affect hemostasis (eg, NSAIDS, platelet inhibitors, other anticoagulants), in patients with a history of traumatic or repeated epidural or spinal punctures, or a history of spinal deformity or spinal surgery. Monitor for signs of neurologic impairment (eg, midline back pain, numbness/weakness of legs, bowel/bladder dysfunction); prompt diagnosis and treatment are necessary. In patients who are anticoagulated or pharmacologic thromboprophylaxis is anticipated, assess risks versus benefits prior to neuraxial interventions. The optimal timing between the administration of rivaroxaban and neuraxial procedures is not known. Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of rivaroxaban is low. European guidelines recommend waiting at least 22 to 26 hours following the last rivaroxaban dose when using prophylactic dosing (eg, 10 mg once daily) before catheter placement or lumbar puncture (Gogarten 2010). When higher doses are used (eg, 20 mg once daily), some suggest avoidance of neuraxial procedures for at least 48 hours (Rosencher 2013). In patients who have received neuraxial an