Mechanism of Action

• Local fibrinolysis by binding to fibrin, converts entrapped plasminogen to plasmin

Pharmacokinetics

• Half-Life:
  4.2 h (12 to < 18 years)
  3 h (2 to 11 years)
  1.9 h (6 months to 1 year)
  1.6 h (< 6 months)
• Metabolism: Primarily proximal small intestine and some gastric absorption
• Time to peak: 2 to 4 hours
• Oral availability: ~66% (fasting); ~80-100% (with food)
• Excretion: ~2/3 primarily cleared via Hepatic degradation via the cytochrome P450 pathway~1/3 (35%) Renal elimination as unchanged drug (~1/3 also eliminated as inactive metabolites)
• Protein binding: ~90%

Dosing – Pediatric

• 1 mg/mL oral suspension
• Pediatric patients from birth to less than 18 years after at least 5 days of initial parenteral anticoagulant treatment, as well for thromboprophylaxis in pediatric patients 2 years and older with congenital heart disease after the Fontan procedure.
• Do NOT use in patients with mechanical prosthetic heart valves. Rivaroxaban isn’t recommended in patients with antiphospholipid syndrome. Rivaroxaban is indicated for pediatric VTE treatment after 5-10 days of parenteral anticoagulation.

**Thromboprophylaxis after Fontan procedure (children >2 years and adolescents):

Oral Suspension
7 to 7.9 kg	1.1 mg PO q12h
8 to 9.9 kg	1.6 mg PO q12h
10 to 11.9 kg	1.7 mg PO q12h
12 to 19.9 kg	2 mg PO q12h
20 to 29.9 kg	2.5 mg PO q12h
30 to 49.9 kg	7.5 mg PO q24h
Oral Tablet
>50 kg	10 mg PO q24h

VTE treatment and prophylaxis (after ≥5 days of initial parenteral treatment*): 

Oral Suspension
2.6 to 2.9 kg	0.8 mg PO q8h
3 to 3.9 kg	0.9 mg PO q8h
4 to 4.9 kg	1.4 mg PO q8h
5 to 6.9 kg	1.6 mg PO q8h
7 to 7.9 kg	1.8 mg PO q8h
8 to 8.9 kg	2.4 mg PO q8h
9 to 9.9 kg	2.8 mg PO q8h
10 to 11.9 kg	3 mg PO q8h
12 to 29.9 kg	5 mg PO q12h
30 to 49.9 kg	15 mg PO q24h
Oral Tablet
30 to 49.9 kg	15 mg PO q24h
>50 kg	20 mg daily

**It is important to note that the pediatric clinical trials for rivaroxaban continued treatment dosing for secondary prevention of VTE in children beyond the 3-month acute treatment phase, but the dosing regimen was NOT changed. There is no data to support using dosing for thromboprophylaxis after Fontan procedure for patients whom are non-Fontan needing secondary VTE prevention management. If needed, one could consider lowering the dose in a similar ratio to maintain quality of life, although there is no data to support this. One could also consider continuing treatment dosing, given the low bleeding rate in clinical trials and the available data on efficacy.

Monitoring

Anticoagulation Monitoring Parameter and Reference Range Routine coagulation testing is not required for monitoring of rivaroxaban. If monitoring is indicated, rivaroxaban anti-Xa activity assay is the preferred test to extrapolate rivaroxaban concentrations in ng/ml. Therapeutic range not defined. Dose adjustment based on results not yet established. Observed peak and trough concentrations in patients exposed to therapeutic dosing have been reported (if rivaroxaban calibrated assay is available, the expected observed peak levels for rivaroxaban are 90–195 ng/mL for 10 mg and 189–360 ng/mL for 20 mg dose. The expected trough is < 30 ng/mL).

Initiating Therapy

• Minimum Monitoring Requirements: Prior to initiation of therapy, but no longer than 48 hours before, the following labs should be checked: CBC, coagulation profile (PT, PTT, fibrinogen activity), hepatic function panel, creatinine, urine pregnancy if applicable
• Administration: Begin treatment only if tolerating full feeds.

Dosage Forms

• Rivaroxaban is available as tablets or oral suspension. Rivaroxaban 2.5 mg tablets are not recommended for use in pediatric patients. For pediatric patients who cannot swallow the 10 mg, 15 mg, or 20 mg tablet whole, transition to oral suspension

Tablets	Bottles containing either 20 mg, 15 mg, 10 mg, or 2.5 mg. There is also starter packet containing 51 tablets: 42 tablets of 15 mg and 9 tablets of 20 mg.
Oral Suspension	1 mg/mL oral suspension

• Patient assistance program for drug: Johnson & Johnson

Administration	Rivaroxaban can be administered via mouth with food, G-tube or NG tube.
Splitting/crushing	Tablet can be crushed and mixed with applesauce immediately prior to use. Crushed tablets are stable in applesauce for up to 4 hours. After the administration of a crushed rivaroxaban 15 mg or 20 mg tablet, the dose should be immediately followed by food. Administration with food is not required for the 2.5 mg (rivaroxaban 2.5 mg tablets are not recommended for use in pediatric patients) or 10 mg tablets
Nasogastric/gastric feeding tube	Crushed tablets may be mixed in 50 mL of water and administered; administer the suspension within 4 hours of preparation. Avoid administration distal to the stomach. After the administration of a crushed rivaroxaban 15 mg or 20 mg tablet, the dose should be immediately followed by food/enteral feeding. Administration with food is not required for the 2.5 mg (rivaroxaban 2.5 mg tablets are not recommended for use in pediatric patients) or 10 mg tablets.

Safety Precautions

• Renal impairment: For infants >2.6 kg and < 1 year of age, avoid use when serum creatinine is > 97.5th percentile. For children and adolescents, avoid use when eGFR < 50 mL/min/1.73m2, and no dose adjustment in patients with mild renal impairment (eGFR 50 to ≤ 80 mL/min/1.73m2).
• Hepatic impairment: Avoid use in moderate to severe impairment (Child-Pugh B and C). Avoid use in patients with hepatic disease associated with either coagulopathy leading to a clinically relevant bleeding risk. In Einstein-Jr. trial, exclusion criteria included ALT >5 xULN or total bilirubin > 2xULN with direct bilirubin >20% of the total.
• Drug-Drug interactions:
  • Substrate of p-glycoprotein
    • For the following medications, concomitant use of rivaroxaban should be avoided: dual P-glycoprotein and CYP3A4 Inducers (ex. rifampin, phenytoin, phenobarbital or carbamazepine) and Inhibitors (ex. ketoconazole, itraconazole, posaconazole, ritonavir, erythromycin, all HIV protease inhibitors).
    • Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulant