2 million people use rivaroxaban each year. The benefits are proven, the risks are manageable. Let me what you through what you need to know to minimize risk and optimize efficacy.
Rivaroxaban is an oral anticoagulant. It belongs to the drug class: Direct Oral Anticoagulant (DOAC).
DOACs were introduced in 2010 as an alternative to warfarin. They address alot of the complexities associated with the use of warfarin.
Warfarin is effective within a very narrow therapeutic range. This window of efficacy is easily disrupted by many drug interactions, food interactions and acute illness.
Because of this, warfarin requires regular and often frequent monitoring of blood levels to ensure that patients are anticoagulated enough to prevent thrombosis but not too much that they are high risk for a major bleed. The unit on WARFARIN provides an in depth analysis of the drug.
In comparison, DOACs including rivaroxaban have a better safety and efficacy profile with a more rapid and predictable onset compared to warfarin.
They do not require frequent blood monitoring and there are very few drug and food interactions.
There are 2 subcategories of DOAC based on the mechanism of action: direct thrombin inhibitors and Xa inhibitor. Rivaroxaban is a Xa inhibitor.
How Rivaroxaban Works
Rivaroxaban is a factor Xa inhibitor. It inhibits clotting factor Xa, the first factor activated in the common pathway of the coagulation cascade.
The mechanism of action of rivaroxaban cannot be understood without knowledge of the coagulation cascade. The unit What You Need to Know: Hemostasis covers the coagulation cascade in detail.
The diagram below illustrates where in the coagulation cascade rivaroxaban works.
When is Rivaroxaban Needed?
Rivaroxaban has a growing list of indications including:
- Reduction of risk for stroke and pulmonary embolism in non valvular atrial fibrillation
- Treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE)
- Prevention of DVT and PE in hip and knee replacement and acutely ill patients
- Reduction of risk of major cardiovascular events in patients with coronary artery disease
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ROCKET-AF Trial: The Evidence
The Rocket-AF trial compared rivaroxaban to warfarin in patients with atrial fibrillation in need of anticoagulation.
Efficacy was determined by the rate of stroke or systemic embolism. Safety was compared as the rate of major bleed in each group.
Rivaroxaban was found to be non-inferior (not worse than) to warfarin with no significant difference in major bleed.
How to Use Rivaroxaban
Rivaroxaban is available as an oral tablet and oral 1mg/ml suspension for pediatric patients.
Adult patients who are not able to swallow whole tablets can crush them and mix with applesauce right before administration. Rivaroxaban can also be crushed and suspended in 50cc of purified water for administration via nasogastric and gastric tube. Flush tubes with 15cc before and after. Crushed tablets are stable in applesauce and water for up to 4 hours.
Administration with food increases the bioavailability of rivaroxaban. Doses > 15mg should be administered with meals to achieve a bioavailability of >80%.
This includes doses that are crushed and administered with apple sauce or suspended in water. The recommendation is to take rivaroxaban with the evening meal when it is dosed daily. Lower doses (<15mg) may be administered without regard to meals.
Missed Doses
For patients on a 15mg twice daily regimen who miss a dose, the missed dose should be taken immediately to ensure that the total dose received that day is 30mg. 30mg can be taken as a single dose to achieve this.
Twice daily dosing should resume the next day. For all other twice daily dosing regimens, if a dose is missed, the patient should resume dosing at the next scheduled administration.
For once daily dosing, if missed, take the dose as soon as possible and resume therapy the following day as previously taken.
Drug Interactions with Rivaroxaban
Rivaroxaban is a substrate of CYP3A4/5, CYP2J2, and the P-gp transporters. See the study unit on Cytochrome P450 and P-Glycoproteins to grasp the clinical significance of this group of interactions.
Combined P-gp and strong CYP3A inhibitors increase exposure to rivaroxaban and may increase the risk of bleeding.
Combined P-gp and strong CYP3A inducers decrease exposure to rivaroxaban and may increase the risk of thromboembolic events.
Avoid combined P-gp and strong CYP3A inhibitors and inducers.
Avoid combined P-gp and moderate CYP3A inducers in patients with renal impairment.
Use of Rivaroxaban in Significant Renal Impairment
The manufacturer’s labeling for rivaroxaban reads:
Systemic exposure to rivaroxaban administered as a single 15 mg dose in ESRD subjects dosed 3 hours (post-dialysis) is 56% higher when compared to subjects with normal renal function. The systemic exposure to rivaroxaban administered 2 hours prior to a 4-hour hemodialysis session…is 47% higher compared to those with normal renal function.
The extent of the increase is similar to the increase in patients with CrCl 15 to 50 mL/min taking XARELTO 15 mg. Hemodialysis had no significant impact on rivaroxaban exposure.
In patients with ESRD maintained on intermittent hemodialysis, administration of XARELTO 15 mg once daily will result in concentrations of rivaroxaban and pharmacodynamic activity similar to those observed in the ROCKET AF study. It is not known whether these concentrations will lead to similar stroke reduction and bleeding risk in patients with ESRD on dialysis as was seen in ROCKET AF.
It is important to note that patients with a creatinine clearance of <15ml/min were excluded from the clinical trials. The recommendations above for use in dialysis is based on a single dose pharmacokinetic study that did not evaluate clinical outcomes.
Rivaroxaban is excreted via urine (66% primarily via active tubular secretion ,~36% as unchanged drug; 30% as inactive metabolites); feces (28%,<7% as unchanged drug; 21% as inactive metabolites)
Most drug references, including Lexicomp, recommends against the use of rivaroxaban in patients with a CrCl<15ml/min or on hemodialysis based on expert opinion for the reasons noted above.
How to Dose Rivaroxaban
The standard dosing of rivaroxaban is 20mg once daily in atrial fibrillation. DVT and PE require higher initial doses.
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The information on this website is intended to be used solely for educational and informational purposes. While the content may be about specific medical and health care issues, it is not a substitute for or replacement of personalized medical advice and is not intended to be used as the sole basis for making individualized medical or health-related decisions.