Apixaban

Chemical

Highly selective, oral, reversible direct Xa

Inhibitor of free & clot bound Xa

Use

  1. AF – ↓embolic events
  2. Prevent DVTs post ortho
  3. Treat DVT/PE

Presentation

Tablet 2.5 & 5mg

Dose / Route

↓embolic events: 5mg (PO) BD

DVT prophylaxis: 2.5mg (PO) BD

DVT/PE Rx: 10mg (PO) BD for 7 days → 5mg (PO) BD

Onset / DoA

Onset 4hrs → t ½ 8 – 15hrs

MoA (mechanism)

  • Binds free & clot bound Xa
  • Reversibly
  • Inhibits Xa → ↓thrombin formation
  • No effect on platelet function but ↓thrombin will affect platelet function massively by loss of +ve feedback

PK

A

OBA 50%

D

VD 21L; 88% PPB

High PPB ∴not dialysable

M

t ½ 12hrs

Multiple routes eliminated

D-demethylation & hydroxylation to metabolites

E

25% renally cleared

25% eliminated in faeces

Adverse Effects

  • Bleeding
  • Rash
  • Nausea
  • Anaemia

Monitoring

  • Modified Anti Xa assay specific for APIXABAN
  • PT may be prolonged → but can be normal
  • → in fact all coag profile can be normal despite significant ↑ plasma levels of APIXABAN

Reversal

  • PROTHROMBIN X -VF / contains II, IX, X, some V & VII
  • TRANEXAMIC ACID
  • Haem consult

Adnexanet Alpha = recombinant inactive Xa which acts as a decoy. Unlikely to be available in Australia anytime soon.

Xa inhibitors are highly protein bound & NOT dialysable