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apixaban

apixaban

introduction

  • a trial of the new oral factor Xa inhibitor, apixaban showed that it reduced stroke risk by more than 50% when compared to aspirin alone (3.4% per year on aspirin, 1.6% per year on apixaban), whilst increasing risk of major bleeding from 1.2% per year on aspirin to 1.4% per year on apixaban 5mg bd 1).
  • ARISTOTLE trial compared apixaban with warfarin and showed it was 21% better at reducing stroke, had 30% lower incidence of major bleeding, and reduced all-cause mortality by 11%
  • introduced in Australia on PBS in 2011 as Eliquis 2.5mg film-coated tablets for prevention of post-op deep venous thrombosis (DVT)
  • apixaban was approved on PBS (Auth) in Sept 2013 for use in non-valvular atrial fibrillation with one or more risk factors:
    • PH ischaemic stroke, TIA or non-central nervous system systemic embolism
    • age 75yrs or older
    • hypertension
    • diabetes mellitus
    • heart failure &/or LV ejection fraction 35% or less

dosage in Rx of DVT or PE

  • usual dose 10mg bd for 1wk
  • then 5mg bd
  • (if CrCl > 25mL/min]]

dosage in prevention of post-op DVT

  • usual dose 2.5mg bd
  • start 12-24hrs after surgery
  • take for 32-38 days for hip surgery
  • take for 10-14 days for knee replacement surgery

dosage in non-valvular AF

  • usual dose 5mg bd
  • use 2.5mg bd if 2 or more of:
    • age 80yrs or more
    • body weight 60kg or less
    • serum creatinine 133 umol/L or more
  • patients should be advised not to miss a dose, if they do, they should take a dose immediately then continue with twice daily dosing as before.

switching from warfarin

  • cease warfarin, once INR is below 2, start apixaban

switching from apixaban to warfarin

  • continue apixaban concurrently with starting doses of warfarin
  • after 48hrs of warfarin Rx, start checking INR pre-apixaban dose daily
  • when INR is 2 or higher, cease apixaban

peri-operative patients

  • for procedures with mod. to high risk of bleeding:
    • cease apixaban at least 48hrs prior
    • avoid apixaban in 1st 48hrs post-op
  • for procedures with low risk of bleeding or bleeding risk is controllable:
    • cease apixaban at least 24hrs prior
    • avoid apixaban in 1st 24hrs post-op

contraindications

  • HS to apixaban
  • impaired haemostasis
  • active bleeding
  • hepatic disease with coagulopathy and significant bleeding risk
  • creatinine clearance < 25ml/min
  • concurrent strong inhibitors of CYP3A4 and P-gp such as ketoconazole and HIV protease inhibitors (eg. ritonavir)
  • significant bleeding risk such as rcent peptic ulceration, malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, suspected oesophageal varices, A-V malformations, vascular aneurysms, other major vascular abnormailities
  • concurrent anticoagulants other than when switching to warfarin

common adverse effects

  • haemorrhage - GIT, epistaxis, conjunctival, haematuria, bruising

pharmacology

  • oral factor Xa inhibitor
  • half life 12hrs
  • antithrombotic activity can be assessed by measuring anti-FXa activity (eg. Rotachrom assay)

overdose

  • no antidote available
  • overdosage increases risk of major bleeding
  • activated charcoal within 3hrs of dose may reduce exposure
  • healthy subjects may tolerate 50mg daily for 3 days

Mx of bleeding

  • if minor, cease apixaban or delay next dose
  • if mod-severe bleeding:
    • cease apixaban
    • supportive Rx of bleeding as per usual
    • consider activated charcoal if within 3hrs of last dose
  • if very severe bleeding:
    • as above, plus,
      • consider rFVIIa or PCC
      • consider charcoal filtration or haemodialysis
1)
NEJM 364:9 March 3, 2011 p806-817
apixaban.txt · Last modified: 2020/03/06 09:11 (external edit)