Class
- Anticoagulant
Warfarin
Commonly Prescribed for
(FDA approved in bold)
- Prophylaxis or treatment of thromboembolic complications associated with atrial fibrillation or cardiac valve replacement, and to prevent embolism after myocardial infarction (MI)
- Venous thrombosis/pulmonary embolism
Warfarin
How the Drug Works
- Interferes with the synthesis of vitamin K-dependent clotting factors II, VII, IX, and X and anticoagulant proteins C and S. This decreases risk of thromboembolism
Warfarin
How Long Until It Works
- Anticoagulant effect is delayed for up to 7 days. Heparin is preferred for rapid anticoagulation
Warfarin
If It Works
- Continue to use with appropriate monitoring
Warfarin
If It Doesn’t Work
- Patients can still have stroke despite treatment. Warfarin is only superior to antiplatelet agents for cardiogenic stroke, i.e., related to atrial fibrillation or ventricular thrombus
- Control all stroke risk factors, such as smoking, hyperlipidemia, and hypertension
- For acute events, admit patients for treatment and diagnostic testing. Check international normalized ratio (INR) to determine drug effectiveness
Warfarin
Best Augmenting Combos for Partial Response or Treatment-Resistance
- The combination of aspirin and warfarin in patients with mechanical heart valves appears beneficial despite increased risk of bleeding. Aspirin combined with warfarin did not appear to reduce risk of stroke, systemic embolism, or myocardial infarction in patients with atrial fibrillation in the SPORTIF trials
Warfarin
Tests
- Monitor prothrombin time (PT) and INR to determine effectiveness
Adverse Effects (AEs)
Warfarin
How Drug Causes AEs
- Anticoagulation increases bleeding risk
Warfarin
Notable AEs
- Abdominal pain/cramping, elevated liver enzymes/jaundice, hypotension, weakness, paresthesias, diarrhea, nausea, pruritus and alopecia
Warfarin
Life-Threatening or Dangerous AEs
- Bleeding complications, especially with elevated INRs. Hemorrhage in organs or tissues can cause death
- Necrosis associated with local thrombosis can occur within days of starting treatment
- Patients with venous thrombosis and heparin-induced thrombocytopenia have a risk of limb ischemia, necrosis, and gangrene when stopping heparin and starting warfarin
- May increase risk of cholesterol plaque emboli, typically 3–10 weeks after starting therapy
- “Purple toes syndrome” is a dark, mottled, often purple discoloration on the sides and plantar surface of toes; may be reversible or may lead to necrosis or gangrene
Warfarin
Weight Gain
- Unusual
Warfarin
Sedation
- Unusual
Warfarin
What to Do About AEs
- Stop or lower dose or give vitamin K based on INR and presence of bleeding. For systemic atheroemboli/microemboli, stop drug
Warfarin
Best Augmenting Agents for AEs
- Most AEs cannot be improved by an augmenting agent
Dosing and Use
Warfarin
Usual Dosage Range
- 2–10 mg daily
Warfarin
Dosage Forms
- Tablets: 1, 2, 2.5, 3, 4, 5, 6, 7.5 and 10 mg
- Injection: 5.4 mg (2 mg/mL)
Warfarin
How to Dose
Give once daily, usually starting at 2 to 5 mg/day. Start at lower dose in patients with genetic variations in CYP2C9 or VKORC1 enzymes, the elderly or debilitated and those with potentially greater than expected PT/INR response to warfarin. Adjust dose based on PT/INR determinations. Loading doses of warfarin do not offer more protection against thrombi formation and may increase bleeding risk
Intravenous warfarin dosing is the same as oral. Use in patients without the ability to take oral drugs
- Goal INR is 2–3 for most conditions, including acute MI, atrial fibrillation, pulmonary embolism, venous thrombosis, valvular heart disease, and tissue heart valves
- Goal INR is 2.5–3.5 for patients with mechanical heart valves and for prevention of recurrent MI
- Continue heparin therapy for 4–5 days after starting warfarin until the desired therapeutic response has been reached based on INR. Then stop heparin. Patients with supratherapeutic INR:
- < 5: lower or omit a dose
5 but < 9: if no significant bleeding, omit next few doses, increase monitoring frequency and resume warfarin at a lower dose once INR is therapeutic. When there is significant bleeding, omit dose and give 
5 mg of vitamin K. If there is still significant bleeding and INR has not normalized, give an additional 1–4 mg vitamin K
9: If no significant bleeding, hold warfarin and give 5–10 mg vitamin K orally
- For any serious or life-threatening bleeding, hold warfarin, give vitamin K 10 mg intravenously, and supplement with plasma or prothrombin complex concentrate
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