Apixaban

Apixaban
Systematic (IUPAC) name
1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide
Clinical data
Trade names Eliquis
License data
Routes of
administration		 Oral
Legal status
Legal status
  • UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability ~50%
Protein binding ~87%
Metabolism CYP3A4, CYP3A5, CYP1A2 and others
Biological half-life 9–14 h
Excretion Biliary (75%), renal (25%)
Identifiers
CAS Number 503612-47-3 YesY
ATC code B01AF02 (WHO)
PubChem CID 10182969
IUPHAR/BPS 6390
DrugBank DB07828 YesY
ChemSpider 8358471 YesY
UNII 3Z9Y7UWC1J YesY
KEGG D03213 YesY
ChEMBL CHEMBL231779 YesY
Chemical data
Formula C25H25N5O4
Molar mass 459.497 g/mol
  (verify)

Apixaban, sold under the tradename Eliquis, is an anticoagulant for the treatment of venous thromboembolic events. It is taken by mouth. It is a direct factor Xa inhibitor.

Apixaban was approved in Europe in 2012.[1] It was approved in the U.S. in 2014 for treatment and secondary prophylaxis of deep vein thrombosis (DVT) and pulmonary embolism (PE).[2] It is being developed in a joint venture by Pfizer and Bristol-Myers Squibb.[3][4]

Medical uses

Apixaban is indicated for the following:[5]

Atrial fibrillation

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.[6]

Apixaban and other newer anticoagulants (dabigatran 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.[7]

Side effects

Premature discontinuation of any oral anticoagulant, including apixaban, increases thrombotic event risk. This is not due to any rebound effect from discontinuation. To reduce this risk, administering another anticoagulant is advised.[8]

Bleeding

Apixaban can increase the risk of bleeding and may cause serious, potentially fatal, bleeding. Concurrent use with drugs affecting hemostasis (e.g. other anticoagulants, heparin, aspirin and other antiplatelet drugs, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs) can further increase the risk of bleeding.[5]

One concern with the use of apixaban and the other newer anticoagulants is the absence of well-established protocol for reversal of their activity (no antidote is available). This is an important disadvantage relative to warfarin when bleeding complications occur or when people taking the drugs require emergency surgery.[9]

Spinal puncture

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.[5]

Mechanism of action

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.[5]

FDA approval

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.[2]

During development it was known as BMS-562247-01.

See also

References

  1. ↑ "ELIQUIS® (apixaban) Approved In Europe For Preventing Venous Thromboembolism After Elective Hip Or Knee Replacement" (Press release). Pfizer. April 20, 2012. Retrieved 2012-05-29.
  2. 1 2 "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.
  3. ↑ "Bristol-Myers Squibb News Release 26 April 2007". Archived from the original on 11 September 2007. Retrieved 2007-09-15.
  4. ↑ Nainggolan, Lisa. "Apixaban better than European enoxaparin regimen for preventing VTE". Retrieved 2011-04-01.
  5. 1 2 3 4 "Eliquis (apixaban) [prescribing information]" (PDF). Princeton, NJ: Bristol-Myers Squibb. March 2014. Retrieved 2014-10-29.
  6. ↑ "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.
  7. ↑ 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.
  8. ↑ "ELIQUIS® (apixaban) tablets Factor Xa Inhibitor" (PDF). FDA. August 2014. Retrieved 2014-11-02.
  9. ↑ Enriquez A, Lip GY, Baranchuk A (2015). "Anticoagulation reversal in the era of the non-vitamin K oral anticoagulants". Europace. doi:10.1093/europace/euv030. PMID 25816811.
  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. PMID 22759198.
  11. ↑ Granger, M.D. et. al., Christopher (September 15, 2011). "Apixaban versus Warfarin in Patients with Atrial Fibrillation". New England Journal of Medicine 365 (365): 981–992. doi:10.1056/NEJMoa1107039. PMID 21870978. Retrieved 17 September 2015.
  12. ↑ FDA approves Eliquis to reduce the risk of stroke, blood clots in patients with non-valvular atrial fibrillation
  13. ↑ Neale, Todd (March 14, 2014). "FDA OKs Apixaban for DVT Prevention". MedPage Today. Retrieved 17 September 2015.
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