Apixaban

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Apixaban
Apixaban.svg
Apixaban ball-and-stick model.png
Clinical data
Trade namesEliquis, others
AHFS/Drugs.comMonograph
License data
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability~50%
Protein binding~87%
MetabolismCYP3A4, CYP3A5, CYP1A2 and others
Elimination half-life9–14 h
ExcretionBile (75%), kidney (25%)
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.167.332 Edit this at Wikidata
Chemical and physical data
FormulaC25H25N5O4
Molar mass459.497 g·mol−1
3D model (JSmol)
  (verify)

Apixaban, sold under the trade name Eliquis among others, is an anticoagulant used to treat and prevent blood clots and to prevent stroke in people with atrial fibrillation.[1][2] Specifically it is used to prevent blood clots following hip or knee replacement and in those with a history of prior clots.[1] It is used as an alternative to warfarin and does not require monitoring by blood tests.[1] It is taken by mouth.[1]

Common side effects include bleeding and nausea.[1][2] Other side effects may include bleeding around the spine and allergic reactions.[1] Use is not recommended during pregnancy or breastfeeding.[2] Use appears to be relatively safe in those with mild kidney problems.[2] Compared to warfarin it has fewer interactions with other medications.[3] It is a direct factor Xa inhibitor.[1]

Apixaban was approved for medical use in the United States in 2012.[1] A month supply in the United Kingdom costs the NHS about £57 as of 2019.[2] In the United States the wholesale cost of this amount is about $427.[4] In 2016 it was the 123rd most prescribed medication in the United States with more than 5 million prescriptions.[5]

Medical uses[edit]

Apixaban is used for the following:[6]

Atrial fibrillation[edit]

Apixaban is recommended by the National Institute for Health and Clinical Excellence for the prevention of stroke and systemic embolism in people with non-valvular atrial fibrillation and at least one of the following risk factors: prior stroke or transient ischemic attack, age 75 years or older, diabetes mellitus, or symptomatic heart failure.[7]

Apixaban and other anticoagulants (dabigatran, edoxaban and rivaroxaban) appear equally effective as warfarin in preventing non-hemorrhagic stroke in people with atrial fibrillation and are associated with lower risk of intracranial bleeding.[8]

While apixaban may be used in people with severely decreased kidney function and those on hemodialysis it has not been studied in these groups.[1] Full dose apixaban (5 mg [bid]) can be used, unless at least two of the following characteristics apply: patient age is 80 years or older, body weight is 60 kg or less, and serum creatinine is 1.5 mg/dL or higher, in which case dose reduction to 2.5 mg bid is indicated.[9]

Side effects[edit]

Bleeding[edit]

Apixaban can increase the risk of bleeding which may be serious and potentially fatal. Concurrent use with medications that affect blood clotting can further increase this risk. This includes medications such as other anticoagulants, heparin, aspirin, antiplatelet medications, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs).[6]

Andexanet alfa is an FDA approved antidote for apixaban in people with uncontrolled and life-threatening bleeding events.

Spinal puncture[edit]

When spinal/epidural anesthesia or puncture is utilized, patients who are being treated with anti-thrombotic agents for the prevention of thromboembolic complications are at risk for developing a hematoma, which can cause long-term or permanent paralysis. The risk of this may be increased by using epidural or intrathecal catheters after a surgical operation or from the concurrent use of medicinal agents that affect hemostasis.[6]

Mechanism of action[edit]

Apixaban is a highly selective, orally bioavailable, and reversible direct inhibitor of free and clot-bound factor Xa. Factor Xa catalyzes the conversion of prothrombin to thrombin, the final enzyme in the coagulation cascade that is responsible for fibrin clot formation.[10] Apixaban has no direct effect on platelet aggregation, but by inhibiting factor Xa, it indirectly decreases clot formation induced by thrombin.[6]

FDA approval[edit]

A new drug application (NDA) for the approval of apixaban was submitted to the FDA by Bristol-Myers Squibb and Pfizer jointly after conclusion of the ARISTOTLE clinical trial in 2011.[11] Apixaban was approved for the prevention of stroke in people with atrial fibrillation on December 28, 2012.[12] On March 14, 2014, it was approved for the additional use of preventing deep vein thrombosis and pulmonary embolism in people that had recently undergone knee or hip replacement.[13] On August 21, 2014, the FDA approved apixaban for the treatment of recurring deep vein thrombosis and pulmonary embolism.[14] During its development the drug was known as BMS-562247-01.

See also[edit]

References[edit]

  1. ^ a b c d e f g h i "Apixaban Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 27 March 2019.
  2. ^ a b c d e British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 124–125. ISBN 9780857113382.
  3. ^ Kiser, Kathryn (2017). Oral Anticoagulation Therapy: Cases and Clinical Correlation. Springer. p. 11. ISBN 9783319546438.
  4. ^ "NADAC as of 2019-02-27". Centers for Medicare and Medicaid Services. Retrieved 3 March 2019.
  5. ^ "The Top 300 of 2019". clincalc.com. Retrieved 22 December 2018.
  6. ^ a b c d "Eliquis (apixaban) [prescribing information]" (PDF). Princeton, NJ: Bristol-Myers Squibb. March 2014. Archived from the original (PDF) on 2014-10-24. Retrieved 2014-10-29.
  7. ^ "Apixaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation" (PDF). National Institute for Health and Care Excellence. January 2013. Retrieved 2016-02-26.
  8. ^ Gómez-Outes, A; Terleira-Fernández, AI; Calvo-Rojas, G; Suárez-Gea, ML; Vargas-Castrillón, E (2013). "Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups". Thrombosis. 2013: 640723. doi:10.1155/2013/640723. PMC 3885278. PMID 24455237.
  9. ^ However, the prescription information acknowledges that “clinical efficacy and safety studies with Eliquis did not enroll patients with end-stage renal disease (ESRD) on dialysis”.
  10. ^ Frost C, Wang J, Nepal S, et al. (February 2013). "Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects". Br J Clin Pharmacol. 75 (2): 476–87. doi:10.1111/j.1365-2125.2012.04369.x. PMC 3558798. PMID 22759198.
  11. ^ Granger, Christopher (September 15, 2011). "Apixaban versus Warfarin in Patients with Atrial Fibrillation". New England Journal of Medicine. 365 (11): 981–992. doi:10.1056/NEJMoa1107039. PMC 3861009. PMID 21870978.
  12. ^ Cada, Dennis J.; Levien, Terri L.; Baker, Danial E. (29 May 2013). "Apixaban". Hospital Pharmacy. 48 (6): 494–511. doi:10.1310/hpj4806-494. ISSN 0018-5787. PMC 3839491. PMID 24421512.
  13. ^ Neale, Todd (March 14, 2014). "FDA OKs Apixaban for DVT Prevention". MedPage Today. Retrieved 17 September 2015.
  14. ^ "U.S. FDA Approves Eliquis (apixaban) for the Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE), and for the Reduction in the Risk of Recurrent DVT and PE Following Initial Therapy" (Press release). Pfizer. August 21, 2014. Retrieved 2016-02-26.

External links[edit]