Xarelto® in Practice Q&A

Answers to commonly asked questions about Xarelto

Xarelto is an oral, once-daily direct Factor Xa Factor Xa
Pivotal component of blood clotting cascade. Stimulates the production of thrombin, the enzyme in the coagulation cascade that promotes the formation of blood clots.
inhibitor for:

  • Stroke prevention in adults with non-valvular atrial fibrillation
  • Treatment of pulmonary embolism and treatment of deep vein thrombosis thrombosis
    Formation of a clot inside a blood vessel.
    in adults, prevention of recurrent venous thromboembolism in adults
  • Prevention of atherothrombotic events in adult patients after acute coronary syndrome
  • Prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery

With the introduction of any new therapeutic option, there are often questions regarding its use in clinical practice. These answers to some commonly asked questions are designed to provide further guidance to the physician about the appropriate use of Xarelto.

If the answer to your question is not addressed here, please contact Bayer.

 

What is the evidence to support the use of Xarelto in NVAF NVAF
Non-valvular atrial fibrillation (= NVAF). The term NVAF is restricted to cases in which atrial fibrillation occurs in the absence of rheumatic mitral stenosis or a prosthetic heart valve.
patients undergoing PCI with stenting?

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In PIONEER AF AF
Atrial fibrillation (= AF). A heart rhythm disorder where chambers in the upper heart (atria) beat more rapidly than those in the lower section of the heart. Blood is not pumped out of the upper chambers completely during beating, and may pool and form a clot. A stroke results if a section of clot dislodges from the upper chambers and becomes lodged in the brain.
-PCI, Xarelto significantly reduced clinically significant bleeding in NVAF NVAF
Non-valvular atrial fibrillation (= NVAF). The term NVAF is restricted to cases in which atrial fibrillation occurs in the absence of rheumatic mitral stenosis or a prosthetic heart valve.
patients undergoing PCI with stenting.7 The Xarelto 15 mg OD dose in addition to a P2Y12 inhibitor for a maximum of 12 months post PCI with stent placement has already been adopted in clinical practice.

Xarelto is the only NOAC that is recommended specifically in the focused update of the 2017 ESC Guidelines for DAPT in patients with an indication for an OAC OAC
Oral anticoagulant (= OAC). These are drugs that reduce the ability of the blood to clot.
with a IIb/B recommendation based on the PIONEER AF-PCI results.7,8

Can my NVAF NVAF
Non-valvular atrial fibrillation (= NVAF). The term NVAF is restricted to cases in which atrial fibrillation occurs in the absence of rheumatic mitral stenosis or a prosthetic heart valve.
patients without renal impairment be treated with a reduced dose of NOAC if I consider them to be vulnerable?

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In a retrospective analysis of 14,865 patients from a US administrative database, Yao et al concluded that NOAC underdosing is associated with a higher risk of stroke without any advantages for patient.9

The study found that, among the 13,392 patients with no renal indication for dose reduction, 13.3% were potentially underdosed.9

Suboptimal stroke protection from inappropriate NOAC dosing has no advantages for patient’s safety. There was no statistically significant relationship between dose reduction and risk of stroke or bleeding in patients who received Xarelto.9

Which dose of Xarelto should be used for extended VTE VTE
Venous thromboembolism (= VTE). A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
treatment, for each of my PE PE
Pulmonary embolism (= PE). A potentially fatal condition caused by a blood clot blocking a vessel in the lung: usually the clot originates from a DVT in the legs. PE can result in permanent lung damage.
/DVT DVT
Deep vein thrombosis (= DVT). A blood clot in a deep vein, usually resulting from damage to the vein or blood flow slowing down or stopping. Usually DVTs are found in the leg, but can also be in the arm. Distal DVTs are found in deep veins of the calf, and are the most common type of DVT. Proximal DVTs are found in the legs above the calf muscle up to the waist.
patients?

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Ideally, PE PE
Pulmonary embolism (= PE). A potentially fatal condition caused by a blood clot blocking a vessel in the lung: usually the clot originates from a DVT in the legs. PE can result in permanent lung damage.
/DVT DVT
Deep vein thrombosis (= DVT). A blood clot in a deep vein, usually resulting from damage to the vein or blood flow slowing down or stopping. Usually DVTs are found in the leg, but can also be in the arm. Distal DVTs are found in deep veins of the calf, and are the most common type of DVT. Proximal DVTs are found in the legs above the calf muscle up to the waist.
patients should be assessed for individual risk at month 6 of Xarelto treatment.5

After 6 months, you have the option to reduce the dose of Xarelto to 10 mg once daily. In patients in whom the risk of recurrent VTE VTE
Venous thromboembolism (= VTE). A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
is considered high, like those patients with complicated comorbidities or who have developed recurrent VTE, you can continue to maintain the dose at Xarelto 20 mg once daily. This dosing choice is unique to Xarelto.

How should the dose of Xarelto be modified for patients on extended prevention who have experienced recurrent VTE VTE
Venous thromboembolism (= VTE). A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
?

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From month 6 onwards, the dosage of Xarelto should be increased back to 20 mg OD if patients experienced recurrent VTE VTE
Venous thromboembolism (= VTE). A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
while on Xarelto 10 mg OD.5

Do I need to adjust the dose of Xarelto in patients with renal impairment?

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Xarelto is eliminated via both the faecal and the renal pathway, with two thirds metabolised by the liver and one third of active drug eliminated unchanged via the kidneys. Xarelto does not require any dose adjustments in patients with mild renal impairment (creatinine clearance 50–80 ml/min) or moderate renal impairment (creatinine clearance 30–49 ml/min) for the prevention of VTE VTE
Venous thromboembolism (= VTE). A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
in patients undergoing elective hip or knee replacement surgery, but should be used with caution in patients with severe renal impairment (creatinine clearance 15–29 ml/min), and moderate renal impairment (creatinine clearance 30–49 ml/min) concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations.5

Rivaroxaban clearance is decreased with increasing renal impairment.1 Consequently, and based on the phase III studies (ROCKET AF AF
Atrial fibrillation (= AF). A heart rhythm disorder where chambers in the upper heart (atria) beat more rapidly than those in the lower section of the heart. Blood is not pumped out of the upper chambers completely during beating, and may pool and form a clot. A stroke results if a section of clot dislodges from the upper chambers and becomes lodged in the brain.
), a dose reduction is recommended for SPAF (20 mg OD to 15 mg OD) in patients with moderate renal impairment [CrCl 30–49 ml/min] and severe renal impairment [15–29 ml/min]. For VTE patients with moderate [CrCl 30–49 ml/min] or severe renal impairment [15–29 ml/min] a dose reduction (20 mg OD to 15 mg OD) can be considered if the bleeding risk outweighs the thrombotic risk. No dose adjustment is necessary in patients taking Xarelto 10 mg OD or 2.5 mg BID.

Xarelto has not been studied in the patient population with a creatinine clearance <15 ml/min and its use is not recommended in this patient population.5

Why is no routine coagulation monitoring required?

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Rivaroxaban shows consistent, dose dependent plasma levels across a range of patient populations. With a fixed dose, a wide therapeutic window, few drug interactions, and predictable pharmacodynamics, no routine monitoring of coagulation parameters is required.5,6

Factor Xa Factor Xa
Pivotal component of blood clotting cascade. Stimulates the production of thrombin, the enzyme in the coagulation cascade that promotes the formation of blood clots.
activity closely correlates with the plasma concentration. The prothrombin prothrombin
Inactive version of thrombin, the enzyme in the coagulation cascade that promotes the formation of blood clots. Factor Xa stimulates the conversion of prothrombin to thrombin.
time (PT) varies in a linear dose-dependent fashion with plasma levels of Xarelto.5

How can I measure the anticoagulant anticoagulant
Anticoagulant drugs are used to treat and prevent blood clots. Sometimes referred to as ‘blood thinners’.
effect of rivaroxaban?

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The Anti-Factor Xa Factor Xa
Pivotal component of blood clotting cascade. Stimulates the production of thrombin, the enzyme in the coagulation cascade that promotes the formation of blood clots.
Chromogenic Assay5 and the Prothrombin Prothrombin
Inactive version of thrombin, the enzyme in the coagulation cascade that promotes the formation of blood clots. Factor Xa stimulates the conversion of prothrombin to thrombin.
Time11 (PT), using Neoplastin Plus as reagent, have been identified as suitable coagulation tests for rivaroxaban using validated rivaroxaban calibrators and controls.1,5

The PK profile of rivaroxaban including timing of last drug intake, Cmax and Ctrough has to be taken into account when interpreting results of these tests.5,11

The Anti-Factor Xa Chromogenic Assay accurately estimates rivaroxaban plasma concentration. The PT is prolonged in concentration-dependent fashion,5,12 and in proportion to the increase in anti-Xa activity,13 but the change in PT is smaller and much overlaps within different dose regimens and Cmax/Ctrough levels.13

ALT, alanine aminotransferase; ULN, upper limit of normal; VTE VTE
Venous thromboembolism (= VTE). A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
, venous thromboembolism; OD, once daily; PT, prothrombin prothrombin
Inactive version of thrombin, the enzyme in the coagulation cascade that promotes the formation of blood clots. Factor Xa stimulates the conversion of prothrombin to thrombin.
time; INR INR
International normalised ratio (= INR). A system for assessing the clotting tendency of blood in patients receiving anticoagulant therapy. For patients with atrial fibrillation, the recommended target INR range is between 2 and 3. If the INR is higher than 3, patients are at risk of serious bleeding. If the INR is less than 2, patients are at risk of a blood clotting event.
, international normalised ratio; aPTT, activated partial thromboplastin time; NVAF NVAF
Non-valvular atrial fibrillation (= NVAF). The term NVAF is restricted to cases in which atrial fibrillation occurs in the absence of rheumatic mitral stenosis or a prosthetic heart valve.
, non-valvular atrial fibrillation; PCI, percutaneous coronary intervention; NOAC, non-vitamin K antagonist oral anticoagulant anticoagulant
Anticoagulant drugs are used to treat and prevent blood clots. Sometimes referred to as ‘blood thinners’.
; DAPT, dual antiplatelet therapy; OAC OAC
Oral anticoagulant (= OAC). These are drugs that reduce the ability of the blood to clot.
, oral anticoagulant; AF AF
Atrial fibrillation (= AF). A heart rhythm disorder where chambers in the upper heart (atria) beat more rapidly than those in the lower section of the heart. Blood is not pumped out of the upper chambers completely during beating, and may pool and form a clot. A stroke results if a section of clot dislodges from the upper chambers and becomes lodged in the brain.
, atrial fibrillation; BID, twice daily; HR HR
Hazard ratio (= HR). This is a measure of how often a particular event happens in one group compared to how often it happens in another group, over time.
, hazard ratio; CI, confidence interval; PE PE
Pulmonary embolism (= PE). A potentially fatal condition caused by a blood clot blocking a vessel in the lung: usually the clot originates from a DVT in the legs. PE can result in permanent lung damage.
, pulmonary embolism; DVT DVT
Deep vein thrombosis (= DVT). A blood clot in a deep vein, usually resulting from damage to the vein or blood flow slowing down or stopping. Usually DVTs are found in the leg, but can also be in the arm. Distal DVTs are found in deep veins of the calf, and are the most common type of DVT. Proximal DVTs are found in the legs above the calf muscle up to the waist.
, deep vein thrombosis thrombosis
Formation of a clot inside a blood vessel.
.