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What is Xarelto?
Xarelto, also known as rivaroxaban, is an anticoagulant. It keeps blood from clotting by blocking the creation of thrombin in the clotting sequence. 1 Thrombin is a precursor of fibrin, the “web” that stabilizes clots. 2
Xarelto and other direct thrombin inhibitors are classified as Factor Xa inhibitors (explained more in the following paragraphs).
Comparing Xarelto to Other Blood Thinners
Until Xarelto (and its direct competitors) entered the marketplace, low molecular weight heparin was the “newest” anticoagulant in use. 3 Other versions of heparin, along with warfarin, were approved in the U.S. approximately 60 years ago. 4 5 6
Warfarin has a narrow therapeutic range, necessitating frequent blood monitoring and following a restrictive diet. 7 Xarelto and its competitors were hailed as being more convenient to dose orally—sans blood monitoring—and were approved with no dietary restrictions. 8 Additionally, Xarelto’s manufacturer touted other advantages. Any dose lower than 15 mg didn’t have to be taken with food, and it was the first anticoagulant in its class to offer once-daily dosing.1 (Pradaxa, the first Factor Xa inhibitor to market, requires twice-daily dosing. 9)
Xarelto’s FDA-Approved Uses
|FDA Approval||Indications (Use)|
|July 2011||Reducing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) after knee or hip replacement surgery|
|Nov. 2011||Reducing the risk of stroke in people with nonvalvular atrial fibrillation (NVAF)|
|Nov. 2012||Treating DVT or PE and reducing the risk of recurrence after initial treatment|
How Does Xarelto Work?
The body forms clots via a cascade sequence. Like dominoes falling, one component activates the next. Signaling that activates the start of the cascade can come from an extrinsic source (like getting a cut) or an intrinsic source (like a rough spot developing inside a blood vessel wall due to “bad” fats accumulating). Each source activates a different clotting pathway; but, at a certain point, the two pathways merge to finish the job of creating a clot. Factor Xa is active at the junction where those two pathways become one.2 Xarelto directly inhibits Factor Xa (also called FXa). 13
Xarelto inhibits clotting, whether due to an “extrinsic” factor (a cut) or an “intrinsic” factor (a disease process). “Intrinsic” triggers contribute to strokes, a host of vascular problems and other diseases; so the potential clinical utility for preventing cardiovascular complications by using such an anticoagulant is significant.
According to a February 2016 article published in The New York Times, the U.S. Food and Drug Administration (FDA) is looking into the possibility that a defective blood-testing instrument may have distorted the results of a study, ROCKET AF, involving Xarelto, an anticlotting drug. Based on those possibly inaccurate results, the FDA approved Xarelto for use.
Compromised Clinical Testing
According to a February 2016 article published in The New York Times, the U.S. Food and Drug Administration (FDA) is looking into the possibility that a defective blood-testing instrument may have distorted the results of a study, ROCKET AF, involving Xarelto, an anticlotting drug. Based on those possibly inaccurate results, the FDA approved Xarelto for use. 14
Since Xarelto’s approval several years ago, doctors have prescribed this medication to millions of Americans. Now, Janssen, whose parent company is Johnson & Johnson, and Bayer, manufacturers of Xarelto, are facing lawsuits claiming the drug caused injury to patients. 15
Researchers that oversaw the ROCKET AF study recently conducted an analysis suggesting that the original tests done to measure blood clotting did not significantly compromise safety or efficacy results. Although the FDA is proceeding with its investigation, the agency has advised consumers to continue taking Xarelto according to the manufacturer’s instructions. 16
Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals; 2014. ↩
Introduction to Coagulation. hemedicalbiochemistrypage.org. LLC. 2013. http://themedicalbiochemistrypage.org/blood-coagulation.php. Accessed October 10, 2014. ↩
U.S. Food and Drug Administration website. Generic Enoxaparin Questions and Answers. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm220037.htm. Accessed October 21, 2014. ↩
Kresge N, Larkin C. Boehringer Wins FDA Approval for First Warfarin Rival. Bloomberg News. October 20, 2010. http://www.bloomberg.com/news/2010-10-19/boehringer-wins-u-s-approval-for-first-rival-to-blood-thinner-warfarin.html. Accessed October 17, 2014. ↩
Finkel R. Coming Upon Coumadin: How Warfarin was Discovered. Drugsdb.com website. August 2, 2012. http://www.drugsdb.com/blog/coming-upon-coumadin-how-warfarin-was-discovered.html. Accessed October 21, 2014. ↩
FDA website. Background Information: History of Heparin and FDA Regulation. http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/ScienceBoardtotheFoodandDrugAdministration/ucm399396.htm. Accessed October 21, 2014. ↩
Comparison of Oral Antithrombotics. Pharmacist’s Letter/Prescriber’s Letter. February 2013. PL Detail-Document #290201. ↩
Will Next Generation Oral Anticoagulants Replace Warfarin as Mainstay Therapy? Research and Markets. August 2011. ID 1869007. http://www.researchandmarkets.com/reports/1869007will_next_generation_oral_anticoagulants_replace.pdf. Accessed October 14, 2014. ↩
Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc.; 2014. ↩
Center for Drug Evaluation and Research. Approval package for: Application # 022406Orig1s000. July 1, 2011. ↩
Summary Minutes of the Cardiovascular and Renal Drugs Advisory Committee. FDA Presentation NDA NDA 202439. September 8, 2011. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM278480.pdf. Accessed October 15, 2014. ↩
FDA expands use of Xarelto to treat, reduce recurrence of blood clots. FDA News Release. Nov. 2, 2012. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm326654.htm. Accessed October 12, 2014. ↩
Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus Enoxaparin for Thromboprophylaxis after Hip Arthroplasty. N Engl J Med. 2008;358(26):2765-2775. ↩
http://www.nytimes.com/2016/02/23/business/fda-asks-if-faulty-blood-monitor-tainted-xarelto-approval.html; http://www.cbsnews.com/news/did-heart-drug-makers-withhold-data-from-medical-journal/ ↩
http://www.nytimes.com/2016/02/23/business/fda-asks-if-faulty-blood-monitor-tainted-xarelto-approval.html; http://www.cbsnews.com/news/did-heart-drug-makers-withhold-data-from-medical-journal/; http://www.nejm.org/doi/full/10.1056/NEJMc1515842 ↩