NOACs and DOACs
Terminology
NOACs
Novel / New/ Non-Vitamin K Oral Anticoagulants
DOACs
Direct Oral Anticoagulants
DOACs
Warfarin
Pharmacology
MOA
Interactions
Resource Implications
VKA
Vitamin K Antagonists (Warfarin)
Vitamin K antagonists
Inhibits Factors II, XII, IX, X
Drugs 💊
Direct Factor Xa Inhibitors 🦊
Apixaban (Eliquis)
Edoxaban (Lixiana)
Rivaroxaban (Xarelto)
Thrombin Inhibitor (IIa) 🐻
Dabigatran (Pradaxa)
Common Coagulation Pathway
Steps
- Initiaion phase
- Amplification propogation phase
- Clot formation
Indications
Apixaban
Dabigatran
Edoxaban
Rivaroxaban
Stroke Prevention in NVAF
Treatment of DVT and PE
Prevention of DVT and PE
VTE prevention following elective TKR or THR surgery
Prevention of atherothrombotic events in pateints with CAD or PAD ( in combination with aspirin
Bleeding Risk HAS-BLED
H Hypertension (1)
A Abnormal (Renal function (1) or Liver function (1))
S Stroke (1)
B Bleeding (1)
L Labile INR (1)
E Elderly (>65) (1)
D Drugs or alcohol (2)
HAS-BLED score >=3 High risk
Peak effect 4-5 days
Half life 40hrs
Monitoring availble : yes, INR
No renal clearance
Benefits
Instantly recognisable
Can be monitored
Experience with use in invasive procedures (ablations, pacemaker)
Reversible (Vit K)
Limited renal adjustments needed
Experience with dual antiplatelet agents
Cost effective
Disadvantages
Vit K antagonist - many food interactions
Narrow therapeutic index
Variations in anticoagulant effect
Drug interactions effecting metabolisms
Need for regular monitoring
Variation in monitoring services ( venous bloos samples to lab, POC devices)
Onset 3-4 hrs
Half life 12 hrs
Dose in NVAF (Nonvalvular atrial fibrillation) 5 mg BD
Not recommended in pts undergoing dialysis
NVAF adjustments
- Age >80 yrs
- Renal function (serum creatintin >=133 μmol / L)
- Weight <60kg
Onset 2-4 hours
Half life 5-9 hours
Dose
Standard dose NVAF 20mg OD
Adjust
- Renal function
Not recommended if CrCl <15ml/min
- Interactions
P-gp and stong CYP 3A4 inhibitors
Rionavir
Iopinavir
Ketoconazole
Itraconazole
Efficacy unaffected by weight
Bioavailability increases with food ( 20mg and 15 mg - take with food)
Onset 1-3 hours
Half life 10-14 hours
Dosing
Standard dose in NVAF 6mg OD
- Renal function
Not recommended for reduced CrCl <15ml/min or dialysis and increased CrCl >95ml/min
- Body weight <=60kg
3 Interactions
Ciclosporin
Dronedarone
Erythromycin
Ketoconazole
Not licensed for VTE prophylaxis
Onset immediate - Peak at 2-3 hours
Half life 12-14 hours
Dosing
Standard in NVAF 150mg BD
Adjust for
- Age
Over 80 yrs
Over 75 yrs and reduced renal function / GORD/ high bleeding risk
- Renal Function
Contraindication CrCl >30ml/min
- GORD (Gastroesophageal reflux disease)
- Interactions
Verapamil
Reversal agent
Idarucizumab approved
Monoclonal antibody binds dabigatran with 350x affinity as thrombin
Binds free and thrombin bound dabigatran
5mg IV
Reversal in minutes
Benefits 👍
- No routine monitoring required
- Braoder therapeutic window than warfarin
- Fixed dose regimen
- No food interactions
- Fewer drug interactions than warfarin
- Potentially better patient compliance (less monitoring, less interations)
Disadvantages 👎
- Lack of experience of LT use compared with warfarin / aspirin
- Short half life rewuires strict compliance
- Inability to monitor anticoagulation or validate patient compliance
- Costly
- Age, weigth and renal function influence dosing
Safety Concerns 🚩
- Correct indication, dose, frequency
- Contraindications and cautions
- Missed doses/ adherence and persistence
Prescribing ✍
Assesment Prior to Dosing
- DOAC choice
- Dose
- Contraindication
- Considerations (age, weight, renal function)
- Counselling patient
New pts
Missed doses
Swithing DOACs / from warfarin
- Indication
Patients Characteristics
- High bleeding risk
- Renal impairment
- Gastro issues
- Previous stroke
- Pt preference
Dosing
- Correct DOAC
- Correct Dose
- Correct Frequency
Discharge prescription should clearly state DURATION OF TREATMENT
If Apixaban - how many further days of 10mg BD before reducing to 5mg BD
Contraindications / Cautions
Drug interactions
DOAC-PgP interactions
Increased DOAC absorbed
Increased risk of bleeding
P-glycoprotein transporter in intestinal mucosal cells regulates drug uptake
Verapamil inhibits PgP
CYP3A4
Metabolises Apixaban and Rivaroxaban
Enzyme inducers reduce DOAC plasma conc
Increased risk of thromboembolic events
Enzyme inhibitors increases DOAC plasma conc
Increased risk of bleeding
Cautions
Oher anticoagulants
Antiplatelets
NSAIDs
HAS-BLED >= 3 (AF patients)
DOAC Monitoring Requirements ⚖
- Requirement of DOAC
- Renal function
Using Cockcroft-Gault equation
- Age
- Weight
- Interactions
- Dose adjustments
