Rivaroxaban
Clinical data | |
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Trade names | Xarelto, others |
Other names | BAY 59-7939 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a611049 |
License data |
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Pregnancy category |
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Routes of administration | By mouth |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 80–100%; Cmax = 2–4 hours (10 mg oral)[4] |
Metabolism | CYP3A4, CYP2J2 and CYP-independent mechanisms[4] |
Elimination half-life | 5–9 hours in healthy subjects aged 20 to 45[4][7] |
Excretion | 2/3 metabolized in liver and 1/3 eliminated unchanged[4] |
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JSmol) | |
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Rivaroxaban, sold under the brand name Xarelto among others, is an
Common side effects include bleeding.
Rivaroxaban was patented in 2007 and approved for medical use in the United States in 2011.[10] In the United States, it will not be available as a generic medication until 2024.[11][12] It is on the World Health Organization's List of Essential Medicines.[13] In 2021, it was the 86th most commonly prescribed medication in the United States, with more than 8 million prescriptions.[14][15]
Medical uses
In those with non-valvular
In July 2012, the UK's
Contraindications
Because of the difficulty associated with managing bleeding, rivaroxaban should be discontinued at least 24 hours before surgery, then restarted as soon as adequate hemostasis is established.[20]
Dosing recommendations do not recommend administering rivaroxaban with drugs known to be strong combined CYP3A4/P-glycoprotein inhibitors because this results in significantly higher plasma concentrations of rivaroxaban.[5][21]
Adverse effects
The most serious adverse effect is bleeding, including severe internal bleeding.[22][23][24] Rivaroxaban is associated with lower rates of serious and fatal bleeding events than warfarin but is associated with higher rates of bleeding in the gastrointestinal tract.[18]
As of 2015[update], post-marketing assessments showed liver toxicity, and further studies are needed to quantify this risk.[25][26] In 2015, rivaroxaban accounted for the highest number of reported cases of serious injury among regularly monitored medications to the FDA's Adverse Events Reporting System (AERS).[27]
Reversal agent
In October 2014, Portola Pharmaceuticals completed Phase I and II clinical trials for andexanet alfa as an antidote for Factor Xa inhibitors with few adverse effects, and started Phase III trials.[28][29] Andexanet alfa was approved by the U.S. Food and Drug Administration in May 2018, under the trade name AndexXa.[30][31]
Mechanism of action
Rivaroxaban inhibits both free and bound
Unfractionated
Rivaroxaban has predictable
Chemistry
Rivaroxaban bears a striking
History
Rivaroxaban was initially developed by
Society and culture
Economics
Using rivaroxaban rather than warfarin costs 70 times more, according to
Legal status
In September 2008,
In the same month, the European Commission also granted marketing authorization of rivaroxaban to prevent venous thromboembolism in adults undergoing elective hip and knee replacement.[44][6]
In July 2011, the US Food and Drug Administration (FDA) approved rivaroxaban for prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in adults undergoing hip and knee replacement surgery.[45]
In November 2011, the US FDA approved rivaroxaban for stroke prevention in people with non-valvular atrial fibrillation.[46]
Legal action
On March 25, 2019, over 25,000 lawsuits over rivaroxaban in the US were settled for $775 million to get paid out to those affected. Plaintiffs accused the drugmakers of not warning about the bleeding risks, claiming their injuries could have been prevented had doctors and patients been provided adequate information.[47]
Research
Researchers at the
Under-representation of racial minorities in clinical trials has been noted. Compared to warfarin, efficacy and safety was found to be similar across racial subgroups.[50]
References
- ^ a b "Rivaroxaban Use During Pregnancy". Drugs.com. Retrieved March 3, 2019.
- FDA. Retrieved October 22, 2023.
- ^ Xarelto (Bayer Australia Ltd)
- ^ a b c d e f g "Xarelto 2.5 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). August 9, 2022. Retrieved November 9, 2022.
- ^ a b c "Xarelto- rivaroxaban tablet, film coated Xarelto- rivaroxaban tablet, film coated Xarelto- rivaroxaban kit". DailyMed. Retrieved November 13, 2020.
- ^ a b "Xarelto EPAR". European Medicines Agency (EMA). September 17, 2018. Retrieved November 13, 2020.
- PMID 19561868.
- ^ a b c d e f "Rivaroxaban Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved March 3, 2019.
- ISBN 9783319546438.
- ^ "Generic Xarelto Availability". Drugs.com. Retrieved May 9, 2017.
- ^ "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". www.accessdata.fda.gov. Retrieved April 24, 2019.
- ^ "Bayer, J&J Win Ruling That Upholds Patent for Xarelto Drug". April 22, 2019. Retrieved April 24, 2019.
- hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
- ^ "The Top 300 of 2021". ClinCalc. Archived from the original on January 15, 2024. Retrieved January 14, 2024.
- ^ "Rivaroxaban - Drug Usage Statistics". ClinCalc. Retrieved January 14, 2024.
- PMID 30383133.
- PMID 24455237.
- ^ PMID 25486915.
- ^ "Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism". National Institute for Health and Care Excellence (NICE). July 25, 2012. Retrieved January 1, 2020.
- PMID 28008269.
- PMID 23305158.
- ^ "Medication Guide – Xarelto" (PDF). U.S. Food and Drug Administration. Retrieved September 1, 2014.
- ^ "Xarelto Side Effects". WebMD. Retrieved September 1, 2014.
- ^ "Xarelto Side Effects Center". RxList. Retrieved September 1, 2014.
- PMID 25689417.
- PMID 24681117.
- ^ Schroeder C. "ISMP Ranks Xarelto Most Dangerous Drug in the United States". DrugNews. Retrieved August 10, 2016.
- ^ Schroeder C. "Possible Antidote Could Help Blood Thinner Patients In Bleeding Emergencies". DrugNews. Retrieved August 20, 2015.
- S2CID 22593448.
- ^ "Accelerated Approval for AndexXa" (PDF). FDA. Retrieved August 1, 2018.
- ^ "U.S. FDA Approves Portola Pharmaceuticals' Andexxa, First and Only Antidote for the Reversal of Factor Xa Inhibitors" (Press release). Portola Pharmaceuticals Inc. May 4, 2018. Retrieved August 1, 2018 – via GlobeNewswire.
- PMID 16161994.
- S2CID 80951298.
- ^ a b Berkrot B (December 23, 2015). "New blood thinner 'antidote' to help doctors move past warfarin". Reuters.
- PMID 18096568.
- PMID 17116766.
- ^ PMID 23458226.
- ^ a b European Medicines Agency (2008). "CHP Assessment Report for Xarelto (EMEA/543519/2008)" (PDF). Retrieved June 11, 2009.[permanent dead link]
- S2CID 220129323.)
{{cite journal}}
: CS1 maint: multiple names: authors list (link - ^ a b "Xarelto FDA Approval History". September 7, 2020.
- S2CID 23498967.
- ^ "Bayer comments on article in The British Medical Journal (BMJ) regarding Xarelto" (PDF). Bayer AG Communications, Government Relations & Corporate Brand. September 29, 2016. Archived from the original (PDF) on January 31, 2017. Retrieved January 19, 2017.
- ^ "Bayer's Xarelto Approved in Canada" (Press release). Bayer. September 16, 2008. Retrieved January 31, 2010.
- ^ "Bayer's Novel Anticoagulant Xarelto now also approved in the EU" (Press release). Bayer. February 10, 2008. Archived from the original on October 22, 2008. Retrieved January 31, 2010.
- Janssen Pharmaceutica. July 1, 2011. Archived from the originalon November 5, 2011. Retrieved July 1, 2011.
- ^ "FDA approves Xarelto to prevent stroke in people with common type of abnormal heart rhythm". US Food and Drug Association. November 4, 2011. Retrieved April 27, 2016.
- ^ "Bayer, Johnson & Johnson settle more than 25,000 lawsuits over blood thinner Xarelto for $775 million". The Washington Post. Retrieved April 7, 2019.
- ^ a b Thomas K (March 1, 2016). "Document Claims Drug Makers Deceived a Top Medical Journal". The New York Times. Retrieved May 3, 2016.
- ^ a b Patel V. "Duke clinical trial under scrutiny in drug case". The Chronicle. Duke Student Publishing Company.
- ^ PMID 21830957.
- ^ "Meet Robert M. Califf, M.D., Commissioner of Food and Drugs". U.S. Food and Drug Administration. Archived from the original on May 15, 2016. Retrieved May 3, 2016.
- PMID 26839968.