WARFARIN DOSING (PHA)

Warfarin affects _ clotting factors

VITAMIN K ANTAGONIST

Warfarin common indications

1) A-FIB stroke prevention (OACS: warfarin or DOACs)

2) VTE treatment

3) VTE prevention

• 2ndary prevention

• mechanical heart valves

Warfaring dosing + factors affecting dosing

STARTING DOSE

• 5mg PO daily

• lower 1-2 mg PO daily (if frail, underweight, Asian)

• bridging therapy

  • LMWH x5 days

  • AND INR = 2 ×2 days

[LMWH: dalteparin, enoxaparin]

WARFARIN MONITORING

INR 2.0 to 3.0

INR full effect in 3-7 days

• don’t adjust dose earlier than 2-3 days….waiting until prothrombin (clot factor 2) is depleted due to long t/2 72 hours

WARFARIN DRUG INTERACTIONS

1) ANTIPLATELET

• ASA

• clopidogrel

2) NSAID

• if need NSAID, consider PPI for GI bleed protection

3) Antibiotics: ↑ INR = bleed risk

• (Rifampin ↓ INR = clot risk)

4) ACUTE INFECTION (cold, flu, fever, diarrhea)

5) ALCOHOL

• acute alcohol drinking = ↑ INR = BLEED

  • alcohol [competes CYP enzyme] …↓ warfarin metabolism leading to accumulation = BLEED

• chronic alcohol drinking = ↓ INR = CLOT

  • ↑ warfarin metabolism = less anticoagulant effect = CLOT

6) SUPPLEMENTS

• ST JOHN’s WORT = CLOT (reduced anticoagulant effect)

• GINGKO BILOBA = BLEED

WARFARIN supplements interaction

WARFARIN REVERSAL

PO vitamin K: 2.5 to 10mg

• (onset) reversal expected in 6 hours

• peak effect in 24 hours

• INR check after 12 hours

IV vitamin K or 4FPC (octaplex, beriplex)….weight based dosing (units/ kg)

• INR decline in 30 minutes…maintained up to ≥ 24 hours

approach to OUT-OF-RANGE INR

1) Compliance

2) drug interactions, supplements

3) changes in diet (consistent diet)

4) recent alcohol intake

5) acute infection

Dose adjustment: SINGLE DOSE CHANGE

0.5 ± INR target

• resume current dose

• 1x dose change: increase/ hold by ½ dose to 1 dose

• repeat INR in 1-2 weeks

dose adjustment: MAINTENANCE DOSE CHANGE

consider if ≥ 2 OUT-OF-RANGE INR TRENDING IN THE SAME DIRECTION

INR dose adjustment (TARGET INR 2.0-3.0)
INR < 2.0

↑ Warfarin WEEKLY dose by 10-15%

• repeat INR w/i 1 week

INR dose adjustment (TARGET INR 2.0-3.0)
INR < 3.1-3.5

• ↑ WARFARIN WEEKLY dose by 10%

repeat INR w/i 2 weeks

INR dose adjustment (TARGET INR 2.0-3.0)
INR < 3.6 to 4.0

• HOLD 0-1 dose

• ↓ weekly dose by 10-15%

repeat INR w/i 1 week

INR dose adjustment (TARGET INR 2.0-3.0)
INR < 4.1 to 8.9

• HOLD 0-2 doses

• ↓ weekly dose by 10-15%

repeat INR in 2 DAYS

INR dose adjustment (TARGET INR 2.0-3.0)
INR > 9.0

• HOLD 2 doses

• ↓ weekly dose by 15-20%

repeat INR: THE NEXT DAY

INR dose adjustment (TARGET INR 2.0-3.0)
INR ≤ 1.5 WITHOUT ANY EXPLANATION

• ↑ weekly dose by 15%

When to consider Vitamin K reversal BASED ON INR

INR > 10

• even in absence of bleeding

CRITERIA FOR BRIDGING THERAPY at perioperative (around surgery)