Rivaroxaban (Xarelto) - Essentia Daily Dose - Essentia Health
Rivaroxaban (Xarelto) - Essentia Daily Dose - Essentia Health
Rivaroxaban (Xarelto) - Essentia Daily Dose - Essentia Health
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<strong>Essentia</strong> <strong>Health</strong> Med Moment<br />
“Short Video Tune-Up”<br />
…A brief overview of a new medication,<br />
or important new medication information<br />
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
by<br />
Richard Mullvain RPH BCPS (AQC)<br />
Current - August 2011
Name of Drug, Description, and Mechanism of Action<br />
Name of Drug: <strong>Rivaroxaban</strong> (<strong>Xarelto</strong>® )<br />
Description: Oral Anticoagulant (Blood-Thinner)<br />
Factor Xa Inhibitor<br />
Mechanism of Action:<br />
<strong>Rivaroxaban</strong> selectively inhibits factor Xa without the<br />
need of cofactor (eg, anti-thrombin III) for activity
New Anticoagulants<br />
ORAL<br />
PARENTERAL<br />
TTP889<br />
TF/VIIa<br />
TFPI (tifacogin)<br />
X<br />
IX<br />
<strong>Rivaroxaban</strong><br />
Apixaban<br />
LY517717<br />
YM150<br />
DU-176b<br />
Betrixaban<br />
TAK 442<br />
IXa<br />
VIIIa<br />
Va<br />
Xa<br />
II<br />
AT<br />
APC (drotrecogin alfa)<br />
sTM (ART-123)<br />
Fondaparinux<br />
Idraparinux<br />
DX-9065a<br />
Dabigatran<br />
IIa<br />
Fibrinogen<br />
Fibrin<br />
Adapted from Weitz & Bates, J Thromb Haemost 2007
Direct Factor Xa inhibition<br />
XIIa<br />
XIa<br />
IXa<br />
Xa<br />
Factor II<br />
(prothrombin)<br />
VIIa<br />
<strong>Rivaroxaban</strong><br />
Apixaban<br />
YM150<br />
DU-176b<br />
LY517717<br />
Betrixaban<br />
TAK 442<br />
Tissue<br />
factor<br />
Fibrinogen<br />
Fibrin clot
FDA Approved Indication<br />
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
On July 1, 2011, FDA approved <strong>Xarelto</strong>®<br />
(<strong>Rivaroxaban</strong>, Janssen Pharmaceuticals, Inc.)<br />
The first oral factor Xa inhibitor approved for<br />
deep vein thrombosis (DVT) prophylaxis in the U.S.<br />
<strong>Xarelto</strong> is indicated for the prevention of deep vein<br />
thrombosis (DVT) and pulmonary embolism (PE) after<br />
elective total hip or knee replacement surgery
Knee or Hip Replacement
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
Approval for DVT prophylaxis after hip and knee<br />
replacement was based on 3 studies in almost<br />
10,000 patients<br />
The comparator was enoxaparin 40 mg once daily<br />
Not Approved for Atrial Fibrillation (Yet)!<br />
Scheduled to go before the FDA Advisory Committee on September 8, 2011<br />
for A-Fib indication<br />
Comparator for A-Fib is Warfarin
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>)<br />
vs<br />
Dabigatran (Pradaxa)<br />
• No Head to Head Data Available!<br />
• Pradaxa, a Direct Thrombin Inhibitor, approved<br />
first for A-Fib, and trying to get approval for DVT<br />
prophylaxis and treatment<br />
• <strong>Xarelto</strong>, a factor Xa Inhibitor, approved first for<br />
DVT prophylaxis, and trying to get approval for<br />
A-Fib and DVT Treatment
Dabi vs. Roxa<br />
RE-LY vs. ROCKET-AF<br />
Indication: Atrial Fibrillation<br />
• Dabi Approved by FDA<br />
October 2010<br />
• Roxi Submit for FDA<br />
approval January 2011
Dabi vs. Roxa<br />
• Open Label<br />
– 18,130 patients<br />
– 71.5 years old avg<br />
Indication: Atrial Fibrillation<br />
RE-LY vs. ROCKET-AF<br />
• Double Blinded<br />
– 14,000 patients<br />
– 73 years old<br />
• Lower Risk Patients<br />
– CHADS2 Score 2.1<br />
• Less HF & Stroke Patients<br />
– 32% & 20%<br />
• INR’s Therapeutic 64%<br />
• Drop Out Rate 20%<br />
• Higer Risk Patients<br />
– CHADS2 Score 3.5<br />
• More HF & Stroke Patients<br />
– 63% % 55%<br />
• INR’s Therapeutic 58%<br />
• Drop Out Rate 25%<br />
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, et al. Dabigatran versus Warfarin K Mahaffey in (Duke Clinical Research Institute, Durham, NC) American Heart<br />
Patients with Atrial Fibrillation. N Engl J Med. 2009; 361:1139-51. (RE-LY)<br />
Association 2010 Scientific Sessions (ROCKET-AF)
Dosing information<br />
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
<strong>Xarelto</strong> is only available as a 10 mg tablet<br />
Fixed dose = 10 mg once daily<br />
Start 6 – 10 hours post-op, after<br />
hemostasis has been established<br />
Treatment duration<br />
12 days after knee replacement<br />
35 days after hip replacement
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®): Kidney or Liver<br />
Not recommended for patients with CrCl
Kinetics<br />
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
Absorption<br />
Tmax, Oral: 2 to 4 hours<br />
Bioavailability, Oral: 80% to 100%<br />
Effects of food: no effect<br />
Distribution<br />
Vd: 50 L<br />
Protein binding, Albumin: 92% to 95%<br />
Metabolism<br />
Liver: major site<br />
Excretion<br />
Fecal: 28%, 7% unchanged<br />
Renal: 66%, 36% unchanged<br />
Dialyzable: No (hemodialysis)<br />
Total body clearance: 10 L/hr<br />
Elimination Half Life<br />
5 to 9 hours (Age 20 – 45 years old)<br />
11 to 19 hours (Elderly)
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
FDA Boxed Warning:<br />
WARNING: SURGICAL SETINGS--SPINAL/EPIDURAL HEMATOMA<br />
Epidural or spinal hematomas may occur in patients who are anticoagulated<br />
and are receiving neuraxial anesthesia or undergoing spinal puncture. These<br />
hematomas may result in long-term or permanent paralysis. Consider these<br />
risks when scheduling patients for spinal procedures. Factors that can<br />
increase the risk of developing epidural or spinal hematomas in these<br />
patients include:<br />
• use of indwelling epidural catheters<br />
• concomitant use of other drugs that affect hemostasis, such as nonsteroidal<br />
anti-inflammatory drugs (NSAIDs), platelet inhibitors, other<br />
anticoagulants<br />
• a history of traumatic or repeated epidural or spinal punctures<br />
• a history of spinal deformity or spinal surgery.<br />
Monitor patients frequently for signs and symptoms of neurological<br />
impairment. If neurological compromise is noted, urgent treatment is<br />
necessary.<br />
Consider the benefits and risks before neuraxial intervention in patients<br />
anticoagulated or to be anticoagulated for thromboprophylaxis<br />
http://www.xareltohcp.com/sites/default/files/pdf/xarelto_0.pdf#zoom=100
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
SPINAL/EPIDURAL HEMATOMA<br />
• Epidural catheter withdrawal should not be<br />
attempted within 18 hours of the last rivaroxaban<br />
dose<br />
• The first/next rivaroxaban dose should be held<br />
for at least six hours<br />
• Withhold rivaroxaban for 24 hours after<br />
traumatic epidural or spinal puncture
Contraindications & Precautions<br />
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
Contraindicated in patients hypersensitive to<br />
rivaroxaban, and patients with active major bleeding<br />
Avoid in significant renal or hepatic impairment<br />
Dosing in pregnancy has not been studied
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®) Drug Interactions<br />
Use rivaroxaban with caution in patients with<br />
increased bleeding risk.<br />
This includes concomitant use of medications that affect<br />
hemostasis<br />
NSAIDs<br />
Other antiplatelet drugs<br />
Other anticoagulants<br />
Fibrinolytics<br />
Avoid concomitant use of clopidogrel (Plavix) unless the<br />
benefit outweighs the increased bleeding risk<br />
Bleeding time was approximately twice the maximum<br />
increase seen with either Plavix or <strong>Xarelto</strong> alone<br />
There was no change in the pharmacokinetics of either<br />
drug
Drug Interactions with <strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
CYP3A4 inhibitors increase rivaroxaban concentrations<br />
ketoconazole, itraconazole, ritonavir, conivaptan<br />
Patients with renal impairment taking p-glycoprotein inhibitors that are<br />
also weak or moderate CYP3A4 inhibitors may be at increased<br />
bleeding risk<br />
Examples include: amiodarone, diltiazem, dronedarone,<br />
felodipine, macrolides, quinidine, ranolazine, and verapamil<br />
Drugs that are both p-glycoprotein inducers and strong CYP3A4 inducers<br />
may<br />
decrease rivaroxaban concentrations.<br />
Examples include: carbamazepine, phenytoin, rifampin, St. John’s wort
Common Side Effects<br />
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
Bleeding is the most common adverse effect<br />
In clinical trials, the risk of bleeding was similar to that of<br />
enoxaparin (Lovenox) 40 mg once daily<br />
Major bleeding occurred in less than 1% of patients<br />
Less common:<br />
Muscle pain or spasm<br />
Syncope<br />
Pruritis or Blister<br />
Hepatobiliary disorders: jaundice, cholestasis, cytolytic hepatitis
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®) : Overdose or Bleeding<br />
There is no antidote!<br />
Interventions appropriate to the specific situation<br />
Hold <strong>Rivaroxaban</strong> (half-life 5 to 13 hours)<br />
Consider Blood transfusion & Compression<br />
Recombinant factor VIIa, prothrombin complex concentrate, or activated<br />
prothrombin complex concentrate can be considered, but have not been studied<br />
for reversing the effects of rivaroxaban<br />
Protamine and vitamin K would not be expected to help<br />
Due to the high plasma protein binding, rivaroxaban is not expected<br />
to be dialyzable
Final Comments<br />
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
<strong>Xarelto</strong> will cost about $8 per day<br />
vs around $25 to $50 for enoxaparin once-daily<br />
Can be taken with or without food<br />
May improve adherence over low-molecular weight heparin<br />
Avoids the concern of heparin-induced thrombocytopenia and<br />
thrombosis (HITT), and it does not require laboratory monitoring
<strong>Rivaroxaban</strong> (<strong>Xarelto</strong>®)<br />
• Links for more information on this drug:<br />
• http://www.xareltohcp.com/sites/default/files/pdf/xarelto_0.pdf#zoom=100<br />
• http://www.thomsonhc.com/micromedex2/librarian/ND_T/evidencexpert/ND<br />
_PR/evidencexpert/CS/D37768/ND_AppProduct/evidencexpert/DUPLICATI<br />
ONSHIELDSYNC/03791E/ND_PG/evidencexpert/ND_B/evidencexpert/ND_<br />
P/evidencexpert/PFActionId/evidencexpert.IntermediateToFullDocumentLin<br />
k/docId/929924/contentSetId/100/title/<strong>Rivaroxaban</strong>/servicesTitle/Rivaroxaba<br />
n<br />
• http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspxnidchk=<br />
1&cs=CEPDA&s=PL&pt=6&fpt=20&dd=270806&pb=PL
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