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Margaret Jin, BScPHM, PharmD, CGP November 2007. Learning Objectives. To review the mechanism of action, indications, contraindications, adverse reactions, & common drug interactions of warfarin To provide effective patient education To understand general concepts in warfarin dosing

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learning objectives
Learning Objectives
  • To review the mechanism of action, indications, contraindications, adverse reactions, & common drug interactions of warfarin
  • To provide effective patient education
  • To understand general concepts in warfarin dosing
  • To be able to use vitamin K1 appropriately
mechanism of action
Mechanism of Action

Vitamin K

Antagonism

of

Vitamin K

VII

Synthesis of Non Functional Coagulation Factors

IX

X

II

Warfarin

indications recommended therapeutic range
Indications & Recommended Therapeutic Range

Chest 2004;126(3 Suppl):204S-233S

contraindications
Contraindications
  • Pregnancy
  • Risk of hemorrhage > clinical benefits
    • Active hemorrhage (e.g., GI bleed)
    • Uncontrolled alcohol/drug abuse
    • Unsupervised dementia/psychosis
  • Unable to monitor INR
adverse effects
A/E to report to MD:

Blood in stools or urine

Excessive menstrual bleeding

Bruising

Excessive nose bleeds/bleeding gums

Persistent oozing from superficial injuries

Intracranial Hemorrhage

Factors that may influence bleeding risk:

Intensity of anticoagulation

Concomitant clinical disorders

Hx of bleeding

Hx of stroke

Renal/Liver insufficiency

Anemia

Hypertension

Concomitant use of other medications

Adverse Effects

Chest 2004;126(3):204S-233S

adverse effects8
Skin necrosis – 0.01-0.1%

Day 3 – 8

Painful skin lesions

Purple toe syndrome

Week 3 – 8

Blue/purple toes/fingers

Allergic Dermatitis

Skin rash, hives, itching

Vasculitis

Fever, itching, skin sores or blisters

Adverse Effects
pharmacokinetics
Absorption

Rapid absorption

Food does not affect absorption

Distribution

99% protein bound

Metabolism

Liver

Cytochrome P450 2C9

Pharmacokinetics
drug interactions
Increase Warfarin Response

NSAIDS, ASA

Acetaminophen > 2g/d

Amiodarone

Quinolones (e.g., Cipro), sulfonamides, metronidazole

Fibrates

Ginkgo, Garlic, Ginseng

Grapefruit

Decrease Warfarin Response

Phenobarbital

Carbamazepine

Phenytoin

Vitamin K rich foods

Green leafy vegetables

Drug Interactions
effective patient education
Effective Patient Education
  • Teach basic concepts of safe, effective anticoagulation
  • Discuss importance of regular INR monitoring
  • Counsel on use of other medications, alcohol
  • Develop creative strategies for improving compliance
    • Evening, same time
    • Dosettes, blisterpacks
warfarin tablets
1mg – pink

2mg – lavendar

2.5mg – green

3mg – tan

4mg – blue

5mg – peach

6mg – teal

7.5mg – yellow

10mg - white

Warfarin Tablets
warfarin maintenance target inr 2 0 3 0
Warfarin MaintenanceTarget INR 2.0 - 3.0

^If INR is 1.8 to 1.9, consider no change with repeat INR in 7 to 14 days

*If INR is 3.1 to 3.2, consider no change with repeat INR in 7 to 14 days

warfarin maintenance target inr 2 5 3 5
Warfarin MaintenanceTarget INR 2.5 - 3.5

^If INR is 2.3 to 2.4, consider no change with repeat INR in 7 to 14 days

*If INR is 3.6 to 3.7, consider no change with repeat INR in 7 to 14 days

warfarin dosing schedule

3

3

3

3

3

3

3

3

3

3

3

3

3

3

3

3

Warfarin Dosing Schedule

Total

Weekly

Dose

Mon

Tue

Wed

Thu

Fri

Sat

Sun

21 mg

19 mg

2

2

 10%

 15%

18 mg

2

2

2

warfarin dosing schedule16

3

3

3

3

3

3

3

3

3

3

3

3

3

3

3

3

Warfarin Dosing Schedule

Total

Weekly

Dose

Mon

Tue

Wed

Thu

Fri

Sat

Sun

21 mg

23 mg

4

4

 10%

 15%

24 mg

4

4

4

types of bleeds
Types of Bleeds
  • No significant bleeding = Minor bleeding
    • Bruises
    • Reported, but does not require additional testing, referrals or visits
  • Serious bleeding = Major bleeding
    • Black tarry stools, blood in urine, hematoma
    • Requiring treatment, medical evaluation or at least 2 units of blood
  • Life-threatening bleeding
    • Intracranial hemorrhage, retroperitoneal bleed, leading to cardiac arrest, surgical/angiographic intervention, or irreversible sequelae
warfarin management
Warfarin Management

*High risk = factors that may influence bleeding risk - Hx of bleeding, stroke, renal & liver insufficiency, anemia, hypertension, other medications

warfarin management20
Warfarin Management
  • Serious bleeding, any INR
    • Hold Warfarin
    • Give Vitamin K1 10mg slow IV plus fresh plasma or prothrombin complex concentrate, depending on urgency
    • Repeat Vitamin K1 every 12 hours as needed
  • Life-threatening bleeding, any INR
    • Hold warfarin
    • Give prothrombin complex concentrate (or recombinant factor VIIa as an alternative) supplemented with vitamin K1 10mg slow IV; repeat as needed
vitamin k1 phytonadione
Vitamin K1, Phytonadione
  • Injection Formulation
    • 10mg/mL – 1mL vial
    • 2mg/mL – 1mL vial
  • Tablets are not available in Canada
  • Administer PO or IV
  • Do not administer SC
  • Elimination Half-life = 26-193 hours
summary
Summary
  • Use clinical judgment
  • Educate patient
  • Adjusting warfarin dose is better than adjusting patient’s quality of life
  • Monitor INR appropriately
  • Refer to Thrombosis Clinic if necessary
references
References
  • The Thrombosis Interest Group of Canada (www.tigc.org)
  • Vitamin K diet
    • www.gicare.com/pated/edtot39.htm
    • http://www.drgourmet.com/warfarin/vitaminkcontent.pdf
  • Ansell J, et al. The pharmacology and management of the vitamin K antagonists. Chest 2004;126:204S-233S
  • Singer DE, et al. Antithrombotic therapy in atrial fibrillation. Chest 2004;126:429S-456S
  • http://www.ccs.ca/download/consensus_conference/consensus_conference_archives/2004_Atrial_Fib_full.pdf