3. Development
Traditional anticoagulants have 2 major limitations:
-
Narrow therapeutic window of adequate anticoagulation without
bleeding
-
Highly variable dose-response, requiring monitoring by lab testing
These limitations have provided impetus for development of other
antithrombotic agents.
3 new oral anticoagulants (NOAC) dagibatran, rivaroxaban, apixaban
listed on PBS.
5. Indications
1. Prevention of venous thromboembolism in a patient undergoing
total hip or knee replacement
2. Prevention of stroke or systemic embolism in patients who have
non-valvular atrial fibrillation and has one or more risk factors for
developing stroke or systemic embolism
3. Rivaroxaban for the prevention of recurrent venous
thromboembolism and for the treatment of deep vein thrombosis
and pulmonary embolism.
6. Contraindications
Known hypersensitivity to ingredients of NOAC
Clinically significant active bleeding
Renal impairment <30ml/min
Hepatic disease (child pugh – C)
Recent high risk bleeding lesion (eg. ICH < 6 months)
Pregnancy or breast feeding
Recent stroke, surgery, GI bleed or ulcer
Recent fibronolytic therapy <10days
Concomitant warfarin therapy
7. Features of NOAC
Features to consider
-
Faster onset
-
Shorter ½ life
-
Less drug-drug interactions
-
No need for monitoring with NOACs
-
No antidotes
8. Dosing – Total hip / knee
replacement (VTE prophylaxis)
Dagibatran
Rivaroxaban
Crcl > 50ml / min
220mg once daily
10mg once daily
Crcl 30–50ml / min
150mg once daily
10mg once daily
Crcl 15-30ml / min
contraindicated
contraindicated
Apixaban
2.5mg
once daily
9. Dosing – Non-valvular Atrial
Fibrillation
Dagibatran
Rivaroxaban
Crcl > 50ml / min
150mg twice daily 20mg once daily
Crcl 30-50ml / min
110mg twice daily 15mg once daily
Crcl 15-30ml / min
Contraindicated
Special
populations
Older than 75
Not applicable
years old
110mg twice daily
Apixaban
5mg twice daily
Contraindicated
At least two of
following:
-older than 80 yo
-Weight less than 60kg
-Scr > 133micromol/L
-2.5mg twice daily
10. Dosing – treatment of DVT / PE
Rivaroxaban
Crcl > 30ml / min
15mg twice daily for three weeks, followed by 20mg daily
11. Switching anticoagulants
Switching from
Switching to
Instructions
LMW Heparin
NOACs
When next dose of LMW
Heparin is due
Heparin
NOACs
Immediately when heparin
ceased
Warfarin
NOACs
Start once INR < 2
Dagibatran
LMW heparin / UFH
No bolus required. Start 12
hrs after last dose
Rivaroxaban / Apixaban
LMW heparin / UFH
No bolus required. Start 24
hrs after last dose
NOACs
Warfarin
Continue NOAC and give
warfarin ≤ 5 mg
Stop NOAC once INR ≥ 2 on
2 consecutive days
13. Management of bleeding (Initial Ix)
Seek early haematology advice
Dagibatran:
Measure: FBC, U&E, LFT, coagulation profile, Haemoclot and
dabigatran level
normal TT excludes dabigatran activity
normal aPTT suggests bleeding not due to dabigatran
14. Management of bleeding (Initial Ix)
Rivaroxaban / Apixaban:
Measure: FBC, U&E, LFT, coagulation profile, anti-Xa and
rivaroxaban level
normal PT suggests rivaroxaban level not high
aPTT cannot predict anticoagulant effect
tests are currently inconclusive for apixaban
15. Management of bleeding (mild)
Mild bleeding -
- local haemostatic measures
- delay or discontinue NOAC as required
16. Management of bleeding
(clinically significant)
reduction in Hb >20 g/L or requiring RBC transfusion > 2 units
Stop NOAC therapy
Give oral charcoal if NOAC ingested < 2 hours ago
Maintain adequate hydration to aid drug clearance
Local haemostatic measures: mechanical compression
Transfusion support: RBC transfusion as per Hb level
Consider platelet transfusion if on antiplatelet therapy or if platelets
< 50 x 109/L
Consider radiological and surgical interventions to identify and treat
source of bleeding
17. Management of life threatening
bleeding
bleeding in critical area or organ, loss of Hb > 50 g/L, hypotension not
responding to resuscitation
Get advice of haematologist!!!
T/f to SCGH or RPH
a)FEIBA (factor eight inhibitor bypass activity) 25 -100 International
Units/kg, repeat at 12 hours (probably beneficial)
b)rVIIa 90 microgram/kg every 2-3 hours (possibly beneficial)
c)prothrombinex – VF 25-50 International Units/kg (if not administered
earlier)
d)tranexamic acid 15-30 mg/kg IV for mucosal bleeds
18. Prescribing a new oral
anticoagulant
1. Lab tests – FBC, EUC, LFTs
Contraindications:
-Poor renal function (CrCl ≤ 30 mL/ min, apixaban: ≤ 15 mL/min)
-Liver disease (e.g. ALT > 3x upper limit of normal)
-Hb ≤ 100 g/L (assess risk vs. benefit)
19. Prescribing a new oral
anticoagulant
2. Detailed History
EXCLUSION Criteria:
-Known hypersensitivity to NOAC preparation
-Pregnant or breastfeeding
-Stable warfarin therapy
-Prosthetic heart valve
-Recent stroke
20. Prescribing a new oral
anticoagulant
3. Assess bleeding risk
-Disorder of haemostasis
-Recent surgery (≤ 1 month ago)
-GI bleed ≤ 12 months ago
-Ulcer ≤ 30 days ago
-Fibrinolytic treatment last 10 days
-Dual antiplatelet therapy
21. Prescribing a new oral
anticoagulant
4. Consider contaminant medications
Rivaroxaban / apixaban
-Systemic azole antifungals (except fluconazole)
-HIV-protease inhibitors
Dabigatran
-Systemic azole antifungals (except fluconazole)
-dronedarone
-Simultaneous initiation with verapamil
-cyclosporin and tacrolimus
22. Prescribing a new oral
anticoagulant
Is patient on warfarin?
Stop warfarin
Start NOAC once INR < 2