Dabigatran

Chemical

A benzamidine based thrombin inhibitor (it is a non-peptide reversible thrombin inhibitor)

Use

  1. Prevent strokes in AF
  2. DVT Tx
  3. PE Tx
  4. DVT prevention post ortho-operations

Presentation

75, 110mg capsules of DABIGATRAN ETEXILATE (the prodrug)

Acid-containing capsules to aid absorption (hydrophilic, low permeability → absorbed in stomach & SI)

Dose

110-220mg od

Depends on renal function (↓ = 75mg once daily)

Route

PO

Onset / DoA

30 min onset → TMAX 2hrs → t ½ B 12hrs (anticoag activity)

MoA

UNIVALENT THROMBIN INHIBITOR (reversible)

  • PRODRUG:

Dabigatran etexilate → esterases of liver/plasma →  Dabigatran

  • Binds free & clot bound THROMBIN on catalytic site

Thrombin

  • Fibrinogen → fibrin monomers
  • XIII → XIIIa
  • XI → XIa
  • VIII → VIIIa
  • V → Va
  • Platelet agonist +++
  • Intact endothelium THROMBOMODULIN binds thrombin → activates PrC → anticoagulation

PK

A

Low OBA 6.5% absorbed in acidic stomach & SI

D

VD 60 – 70L; Low PPB

M

Plasma + liver esterases convert to DABIGATRAN (active)

20% conjugated & excreted in biliary system

E

Rest renally excreted unchanged

↓

Dose adjustment for renal impairment

Monitoring

Linear relationship with both tests:

  • Thrombin Clotting Time – very very sensitive to Dabigatran
  • Diltute Thrombin Clotting time (Hemoclot) 

(Although marketed as an anticoag which doesn’t require monitoring…)

Reversal

Idarucizumab