Drug Detail:Xarelto starter pack (Rivaroxaban [ riv-a-rox-a-ban ])
Generic Name: RIVAROXABAN 2.5mg
Dosage Form: tablet, film coated
Drug Class: Factor Xa inhibitors
Recommended Dosage in Adults
| Indication | Renal Considerations * | Dosage | Food/Timing † |
|---|---|---|---|
|
|||
| Reduction in Risk of Stroke in Nonvalvular Atrial Fibrillation | CrCl >50 mL/min | 20 mg once daily | Take with evening meal |
| CrCl ≤50 mL/min ‡ | 15 mg once daily | Take with evening meal | |
| Treatment of DVT and/or PE | CrCl ≥15 mL/min ‡ | 15 mg twice daily ▼ after 21 days, transition to ▼ 20 mg once daily |
Take with food, at the same time each day |
| CrCl <15 mL/min | Avoid Use | ||
| Reduction in the Risk of Recurrence of DVT and/or PE in patients at continued risk for DVT and/or PE | CrCl ≥15 mL/min ‡ | 10 mg once daily, after at least 6 months of standard anticoagulant treatment | Take with or without food |
| CrCl <15 mL/min | Avoid Use | ||
| Prophylaxis of DVT Following: | |||
|
CrCl ≥15 mL/min ‡ | 10 mg once daily for 35 days, 6–10 hours after surgery once hemostasis has been established | Take with or without food |
| CrCl <15 mL/min | Avoid Use | ||
|
CrCl ≥15 mL/min ‡ | 10 mg once daily for 12 days, 6–10 hours after surgery once hemostasis has been established | Take with or without food |
| CrCl <15 mL/min | Avoid Use | ||
| Prophylaxis of VTE in Acutely Ill Medical Patients at Risk for Thromboembolic Complications Not at High Risk of Bleeding | CrCl ≥15 mL/min ‡ | 10 mg once daily, in hospital and after hospital discharge, for a total recommended duration of 31 to 39 days | Take with or without food |
| CrCl <15 mL/min | Avoid Use | ||
| Reduction of Risk of Major Cardiovascular Events (CV Death, MI, and Stroke) in CAD | No dose adjustment needed based on CrCl | 2.5 mg twice daily, plus aspirin (75–100 mg) once daily | Take with or without food |
| Reduction of Risk of Major Thrombotic Vascular Events in PAD, Including Patients after Lower Extremity Revascularization due to Symptomatic PAD | No dose adjustment needed based on CrCl | 2.5 mg twice daily, plus aspirin (75–100 mg) once daily. When starting therapy after a successful lower extremity revascularization procedure, initiate once hemostasis has been established. |
Take with or without food |
Recommended Dosage in Pediatric Patients
Treatment of Venous Thromboembolism and Reduction in Risk of Recurrent Venous Thromboembolism in Pediatric Patients
| Dosage Form | Body Weight | 1 mg XARELTO = 1 mL Suspension | |||
|---|---|---|---|---|---|
| Dosage | Total Daily Dose ‡ | ||||
| Once a Day § | 2 Times a Day § | 3 Times a Day § | |||
|
|||||
| Oral Suspension Only | 2.6 kg to 2.9 kg | 0.8 mg | 2.4 mg | ||
| 3 kg to 3.9 kg | 0.9 mg | 2.7 mg | |||
| 4 kg to 4.9 kg | 1.4 mg | 4.2 mg | |||
| 5 kg to 6.9 kg | 1.6 mg | 4.8 mg | |||
| 7 kg to 7.9 kg | 1.8 mg | 5.4 mg | |||
| 8 kg to 8.9 kg | 2.4 mg | 7.2 mg | |||
| 9 kg to 9.9 kg | 2.8 mg | 8.4 mg | |||
| 10 kg to 11.9 kg | 3 mg | 9 mg | |||
| 12 kg to 29.9 kg | 5 mg | 10 mg | |||
| Oral Suspension or Tablets | 30 kg to 49.9 kg | 15 mg | 15 mg | ||
| ≥50 kg | 20 mg | 20 mg | |||
Dosing of XARELTO was not studied and therefore dosing cannot be reliably determined in the following patient populations. Its use is therefore not recommended in children less than 6 months of age with any of the following:
- Less than 37 weeks of gestation at birth
- Less than 10 days of oral feeding
- Body weight of less than 2.6 kg.
To increase absorption, all doses should be taken with feeding or with food.
Monitor the child's weight and review the dose regularly, especially for children below 12 kg. This is to ensure a therapeutic dose is maintained.
All pediatric patients (except <2 years old with catheter-related thrombosis): Therapy with XARELTO should be continued for at least 3 months in children with thrombosis. Treatment can be extended up to 12 months when clinically necessary. The benefit of continued therapy beyond 3 months should be assessed on an individual basis taking into account the risk for recurrent thrombosis versus the potential risk of bleeding.
Pediatric patients <2 years old with catheter-related thrombosis: Therapy with XARELTO should be continued for at least 1 month in children less than 2 years old with catheter-related thrombosis. Treatment can be extended up to 3 months when clinically necessary. The benefit of continued therapy beyond 1 month should be assessed on an individual basis taking into account the risk for recurrent thrombosis versus the potential risk of bleeding.
Thromboprophylaxis in Pediatric Patients with Congenital Heart Disease after the Fontan Procedure
| Dosage Form | Body Weight | 1 mg XARELTO = 1 mL Suspension | ||
|---|---|---|---|---|
| Dosage | Total Daily Dose * | |||
| Once a Day † | 2 Times a Day † | |||
|
||||
| Oral Suspension Only | 7 kg to 7.9 kg | 1.1 mg | 2.2 mg | |
| 8 kg to 9.9 kg | 1.6 mg | 3.2 mg | ||
| 10 kg to 11.9 kg | 1.7 mg | 3.4 mg | ||
| 12 kg to 19.9 kg | 2 mg | 4 mg | ||
| 20 kg to 29.9 kg | 2.5 mg | 5 mg | ||
| 30 kg to 49.9 kg | 7.5 mg | 7.5 mg | ||
| Oral Suspension or Tablets | ≥50 kg | 10 mg | 10 mg | |
Administration in Pediatric Patients
Food Effect:
For the treatment of VTE in children, the dose should be taken with food to increase absorption.
For thromboprophylaxis after Fontan procedure, the dose can be taken with or without food.
Vomit or Spit up: If the patient vomits or spits up the dose within 30 minutes after receiving the dose, a new dose should be given. However, if the patient vomits more than 30 minutes after the dose is taken, the dose should not be re-administered and the next dose should be taken as scheduled. If the patient vomits or spits up the dose repeatedly, the caregiver should contact the child's doctor right away.
Tablets: XARELTO tablet must not be split in an attempt to provide a fraction of a tablet dose.
For children unable to swallow 10, 15, or 20 mg whole tablets, XARELTO oral suspension should be used. XARELTO 2.5 mg tablets are not recommended for use in pediatric patients [see Use in Specific Populations (8.4)] .
Use in Renal Impairment in Pediatric Patients
Patients 1 Year of Age or Older
- Mild renal impairment (eGFR: 50 to ≤ 80 mL/min/1.73 m 2): No dose adjustment is required.
- Moderate or severe renal impairment (eGFR: <50 mL/min/1.73 m 2): avoid use, as limited clinical data are available.
Estimated glomerular filtration rate (eGFR) can be done using the updated Schwartz formula, eGFR (Schwartz) = (0.413 × height in cm)/serum creatinine in mg/dL, if serum creatinine (SCr) is measured by an enzymatic creatinine method that has been calibrated to be traceable to isotope dilution mass spectrometry (IDMS).
If SCr is measured with routine methods that have not been recalibrated to be traceable to IDMS (e.g., the traditional Jaffé reaction), the eGFR should be obtained from the original Schwartz formula: eGFR (mL/min/1.73 m 2) = k * height (cm)/SCr (mg/dL), where k is proportionality constant:
- k = 0.55 in children 1 year to 13 years
- k = 0.55 in girls > 13 and < 18 years
- k = 0.70 in boys > 13 and < 18 years
Patients Less than 1 Year of Age
Determine renal function using serum creatinine. Avoid use of XARELTO in pediatric patients younger than 1 year with serum creatinine results above 97.5 th percentile, as no clinical data are available.
| Age | 97.5 th Percentile of Creatinine (mg/dL) |
97.5 th Percentile of Creatinine (µmol/L) |
|---|---|---|
| Week 2 | 0.52 | 46 |
| Week 3 | 0.46 | 41 |
| Week 4 | 0.42 | 37 |
| Month 2 | 0.37 | 33 |
| Month 3 | 0.34 | 30 |
| Month 4–6 | 0.34 | 30 |
| Month 7–9 | 0.34 | 30 |
| Month 10–12 | 0.36 | 32 |
Switching to and from XARELTO
Switching from Warfarin to XARELTO - When switching patients from warfarin to XARELTO, discontinue warfarin and start XARELTO as soon as the International Normalized Ratio (INR) is below 3.0 in adults and below 2.5 in pediatric patients to avoid periods of inadequate anticoagulation.
Switching from XARELTO to Warfarin –
- Adults:
No clinical trial data are available to guide converting patients from XARELTO to warfarin. XARELTO affects INR, so INR measurements made during coadministration with warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue XARELTO and begin both a parenteral anticoagulant and warfarin at the time the next dose of XARELTO would have been taken.
- Pediatric Patients:
To ensure adequate anticoagulation during the transition from XARELTO to warfarin, continue XARELTO for at least 2 days after the first dose of warfarin. After 2 days of co-administration, an INR should be obtained prior to the next scheduled dose of XARELTO. Co-administration of XARELTO and warfarin is advised to continue until the INR is ≥ 2.0.
Once XARELTO is discontinued, INR testing may be done reliably 24 hours after the last dose.
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 [see Drug Interactions (7.4)] .
Switching from Anticoagulants other than Warfarin to XARELTO - For adult and pediatric patients currently receiving an anticoagulant other than warfarin, start XARELTO 0 to 2 hours prior to the next scheduled administration of the drug (e.g., low molecular weight heparin or non-warfarin oral anticoagulant) and omit administration of the other anticoagulant. For unfractionated heparin being administered by continuous infusion, stop the infusion and start XARELTO at the same time.
Discontinuation for Surgery and other Interventions
If anticoagulation must be discontinued to reduce the risk of bleeding with surgical or other procedures, XARELTO should be stopped at least 24 hours before the procedure to reduce the risk of bleeding [see Warnings and Precautions (5.2)] . In deciding whether a procedure should be delayed until 24 hours after the last dose of XARELTO, the increased risk of bleeding should be weighed against the urgency of intervention. XARELTO should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established, noting that the time to onset of therapeutic effect is short [see Warnings and Precautions (5.1)] . If oral medication cannot be taken during or after surgical intervention, consider administering a parenteral anticoagulant.
Missed Dose
Adults
- For patients receiving 2.5 mg twice daily: if a dose is missed, the patient should take a single 2.5 mg XARELTO dose as recommended at the next scheduled time.
- For patients receiving 15 mg twice daily: The patient should take XARELTO immediately to ensure intake of 30 mg XARELTO per day. Two 15 mg tablets may be taken at once.
- For patients receiving 20 mg, 15 mg or 10 mg once daily: The patient should take the missed XARELTO dose immediately. The dose should not be doubled within the same day to make up for a missed dose.
Pediatric Patients
- If XARELTO is taken once a day, the patient should take the missed dose as soon as possible once it is noticed, but only on the same day. If this is not possible, the patient should skip the dose and continue with the next dose as prescribed. The patient should not take two doses to make up for a missed dose.
- If XARELTO is taken two times a day, the patient should take the missed morning dose as soon as possible once it is noticed. A missed morning dose may be taken together with the evening dose. A missed evening dose can only be taken in the same evening.
- If XARELTO is taken three times a day, if a dose is missed, the patient should skip the missed dose and go back to the regular dosing schedule at the usual time without compensating for the missed dose.
On the following day, the patient should continue with their regular regimen.
Administration Options
For adult patients who are unable to swallow whole tablets, XARELTO tablets (all strengths) may be crushed and mixed with applesauce immediately prior to use and administered orally. After the administration of a crushed XARELTO 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 or 10 mg tablets [see Clinical Pharmacology (12.3)] .
Administration of XARELTO tablets via nasogastric (NG) tube or gastric feeding tube: After confirming gastric placement of the tube, XARELTO tablets (all strengths) may be crushed and suspended in 50 mL of water and administered via an NG tube or gastric feeding tube. Since rivaroxaban absorption is dependent on the site of drug release, avoid administration of XARELTO distal to the stomach which can result in reduced absorption and thereby, reduced drug exposure. After the administration of a crushed XARELTO 15 mg or 20 mg tablet, the dose should then be immediately followed by enteral feeding. Enteral feeding is not required following administration of the 2.5 mg or 10 mg tablets [see Clinical Pharmacology (12.3)] .
Crushed XARELTO tablets (all strengths) are stable in water and in applesauce for up to 4 hours. An in vitro compatibility study indicated that there is no adsorption of rivaroxaban from a water suspension of a crushed XARELTO tablet to PVC or silicone nasogastric (NG) tubing.
Administration of XARELTO suspension via NG tube or gastric feeding tube: XARELTO oral suspension may be given through NG or gastric feeding tube. After the administration, flush the feeding tube with water.
For the treatment or reduction in risk of recurrent VTE in pediatric patients, the dose should then be immediately followed by enteral feeding to increase absorption. For the thromboprophylaxis in pediatric patients with congenital heart disease who have undergone the Fontan procedure, the dose does not require to be followed by enteral feeding.
An in vitro compatibility study indicated that XARELTO suspension can be used with PVC, polyurethane or silicone NG tubing.
Preparation Instructions for Pharmacy of XARELTO for Oral Suspension
Do not add flavor as product is already flavored (sweet and creamy).
Reconstitute before dispensing:
- Tap the bottle until all granules flow freely.
- Add 150 mL of purified water for reconstitution.
- Shake for 60 seconds. Check that all granules are wetted and the suspension is uniform.
- Push the adaptor into bottleneck and recap bottle.
- The suspension must be used within 60 days.
- Write the "Discard after" date on the bottle and carton.
Dispensing Instructions:
- Dispense in the original bottle.
- Dispense the bottle upright with the syringes provided in the original carton.
Store reconstituted suspension at room temperature between 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Do not freeze.
It is recommended the pharmacist counsel the caregiver on proper use. Alert the patient or caregiver to read the Medication Guide and Instructions for Use.
