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
Licence data EMA:Link
Oral
Pharmacokinetic data
Bioavailability ca. 50%
Half-life 9–14 h
Excretion 75% biliary, 25% renally
Identifiers
503612-47-3 Yes
B01AF02
PubChem CID 10182969
DrugBank DB07828 Yes
ChemSpider 8358471 Yes
UNII 3Z9Y7UWC1J Yes
KEGG D03213 Yes
ChEMBL CHEMBL231779 Yes
Chemical data
Formula C25H25N5O4
459.497 g/mol
 Yes (what is this?)  (verify)

Apixaban (BMS-562247-01, tradename Eliquis) is an anticoagulant for the treatment of venous thromboembolic events. It is a direct factor Xa inhibitor. Apixaban has been available in Europe since May 2012.[1] An FDA decision on apixaban which was expected on June 28, 2012 was initially delayed before final approval on December 28, 2012.[2][3] On August 21, 2014, Pfizer announced that Apixaban was now FDA approved for treatment and secondary prophylaxis of DVT and PE.[4] It is being developed in a joint venture by Pfizer and Bristol-Myers Squibb.[5][6]

Medical uses

Apixaban is indicated for the following:[7]

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.[8]

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.[9]

Side effects

Premature discontinuation of any oral anticoagulant, including apixaban, increases thrombotic event risk for reasons other than pathological bleeding or completion of therapy course. However, it should be pointed out that this is purely due to the risk returning to that without anticoagulant therapy and not due to any rebound effect from discontinuation. To reduce this risk, administering another anticoagulant is advised.[10]

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.[7]

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.[11]

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.[7]

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.[12] Apixaban has no direct effect on platelet aggregation, but by inhibiting factor Xa, it indirectly decreases platelet formation induced by thrombin.[7]

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. ↑ FDA approves Eliquis to reduce the risk of stroke, blood clots in patients with non-valvular atrial fibrillation Huston, Larry (February 29, 2012). "Decision on Apixaban (Eliquis) Pushed Back By Three Months". Forbes. Retrieved 2012-05-29.
  3. ↑ Husten, Larry. "FDA Once Again Delays Approval Of Apixaban (Eliquis)". Forbes. Retrieved 17 July 2012.
  4. ↑ http://www.pfizer.com/news/press-release/press-release-detail/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
  5. ↑ "Bristol-Myers Squibb News Release 26 April 2007". Archived from the original on 11 September 2007. Retrieved 2007-09-15.
  6. ↑ Nainggolan, Lisa. "Apixaban better than European enoxaparin regimen for preventing VTE". Retrieved 2011-04-01.
  7. ↑ 7.0 7.1 7.2 7.3 "Eliquis (apixaban) [prescribing information]" (PDF). Princeton, NJ: Bristol-Myers Squibb. March 2014. Retrieved 2014-10-29.
  8. ↑ "www.nice.org.uk".
  9. ↑ 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. PMID 24455237.
  10. ↑ "ELIQUIS® (apixaban) tablets Factor Xa Inhibitor" (PDF). FDA. August 2014. Retrieved 2014-11-02.
  11. ↑ 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.
  12. ↑ 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.