Summary

• An agent to reverse the anti-factor Xa activity of rivaroxaban is available. Due to the high plasma protein binding, rivaroxaban is not expected to be dialyzable. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of XARELTO.¹
• Overdose of XARELTO may lead to hemorrhage. Discontinue XARELTO and initiate appropriate therapy if bleeding complications associated with overdosage occur. The use of activated charcoal to reduce absorption in case of XARELTO overdose may be considered. Partial reversal of laboratory anticoagulation parameters may be achieved with the use of plasma products. An agent to reverse the anti-factor Xa activity of rivaroxaban is available.¹
• The half-life of rivaroxaban in pediatric patients treated for VTE decreased with decreasing age. Mean half-life values were 4.2 hours in adolescents, 3 hours in children 2 to 12 years of age, 1.9 hours in children 0.5 to <2 years of age, and 1.6 hours in children <0.5 years of age.¹
• Case reports identified during a literature search are included in the CASE REPORTS section for your review.^2-6
• There are no specific recommendations on XARELTO reinitiation after a patient has developed a bleeding event. The decision to reinitiate treatment with XARELTO should be based on your clinical judgement.

CASE REPORTS

Andexanet alfa

Takasaki et al (2021)² reported an 8-year-old, 20-kg female with hypoplastic left heart syndrome status post Fontan procedure and prior thrombosis required anticoagulation to maintain patency of a venous stent. She was initially treated with enoxaparin and warfarin but switched to XARELTO 5 mg twice daily (BID). After three months of taking XARELTO, a computed tomography (CT) of the head showed a large acute-on-subacute subdural hemorrhage. With no available pediatric data, the dose of andexanet was extrapolated from adult guidelines. She was administered 100 mg intravenous (IV) bolus over 15 minutes, followed by 100 mg IV infusion over 100 minutes. She successfully underwent burr hole hematoma evacuation and subdural drain placement immediately after receiving andexanet. Due to the high risk for thrombosis of her stent, unfractionated heparin (UFH) was started on postoperative day (POD) 3, titrated to maintain anti-FXa levels 0.1–0.3 IU/ml. She transitioned to enoxaparin (0.5 mg/kg BID) on POD 6. Five days later (POD 11), she complained of a recurrent headache, and a CT scan demonstrated a new hyperacute left subdural hemorrhage. Her anti-FXa was 0.2 IU/ml. She received protamine to reverse enoxaparin and underwent embolization. One week later, UFH was resumed over 48 hours to a goal anti-FXa of 0.3–0.5 IU/ml before transitioning to enoxaparin (0.5 mg/kg BID). CT head was stable 2 weeks later prior to discharge.

Activated Charcoal

In a case report documented by Mehta et al (2012),³ 1 g/kg of activated charcoal decreased the INR of a 21-month-old female who ingested two 10-mg tablets of XARELTO. The charcoal was given approximately 2 hours after ingestion. The patient's INR peaked to 3.5 approximately 12 hours after ingestion, and subsequently fell to 1.7 at 20 hours after ingestion of the tablets.

In a case report documented by Lynn et al (2015),⁴ a 2-year-old girl that ingested several XARELTO pills (the exact amount was unknown). She presented with no signs or symptoms of bruising or bleeding within 40 minutes of ingestion and was administered a minimal amount of activated charcoal (amount not stated). Laboratory values showed that 100 minutes post-ingestion demonstrated a prothrombin time (PT) of 54 seconds, an international normalized ratio (INR) of 6.1, and a partial thromboplastin time (PTT) of 57 seconds. Hemoglobin was 12.2 g/dL. Eight hours after ingestion, PT was 21.5 seconds, and INR was 1.9. 14.5 hours after ingestion, PT was 16.7 seconds, and INR was 1.1.

In a case report documented by Kilp et al (2016),⁵ a 3-year old girl ingested 60 mg of XARELTO. Upon presentation to the emergency department (ED), the child was asymptomatic with no signs of active bleeding and normal vital signs.  Basic metabolic profile, liver function tests, and complete blood count were within normal limits. Coagulation studies were notable for PT 47.6 seconds, INR 4.4, and PTT 87.4 seconds. Activated charcoal was administered 90 minutes after ingestion. A plasma XARELTO level drawn 9.5 hours after ingestion was 78 ng/mL. The following morning, coagulation studies had normalized with PT 16.7 seconds, INR 1.3, and PTT 40 seconds.

In a case report documented by Ha et al (2020),⁶ a 16-year-old with a history of deep vein thrombosis and pulmonary embolism presented to the ED after intentional ingestion of ten to fifteen 20 mg XARELTO tablets. Initial laboratory studies revealed the following: PT 31.3 sec; INR 2.80; aPTT 37.7 sec; heparin anti-Xa assay (Anti-Xa) 4.82 IU/mL. Kidney function, vital signs and physical examination were all normal on presentation. A single dose of 77g activated charcoal was given in the ED 1.5 hours after presentation. The patient did not receive any reversal agents or blood products and had no bleeding events throughout her hospital course. Despite initially elevated coagulation parameters obtained at four hours post-ingestion, heparin anti-Xa activity decreased by 79.5% and 96.9% at 16 and 28 hours post-ingestion, respectively. XARELTO concentration decreased by 84.8% and 97.2% at 16 and 28 hours post-ingestion, respectively. PT, aPTT, and INR normalized by 28 hours post-ingestion.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 09 December 2023.