Oral Anticoagulants

Warfarin (Coumadin):
  • Inhibits synthesis of vitamin K-dependent clotting factors X, IX, VII, and II (prothrombin).
Pharmacokinetics:
  • Well-absorbed when taken orally.
  • Metabolized by CYP 1A2 and 2C9.
  • Half-life of 3 to 4 days.
Precautions and contraindications:
  • Pregnancy category X.
  • Use cautiously in patients with fall risk, dementia, or uncontrolled hypertension.
  • Avoid in hypermetabolic state.
  • The major adverse drug reaction is bleeding (Antidote is vitamin K).
  • Many drug interactions, including (but not limited to):
    • Antiplatelet drugs.
    • Thrombolytic drugs.
    • Oral contraceptives, carbamazepine, Vitamin K-containing foods, etc.
Clinical use and dosing:
  • Drug of choice for deep vein thrombosis (DVT) and pulmonary embolism (PE).
  • Start at 5 mg per day (7.5 mg/d if weight greater than 80 kg).
  • Consider lower dose in the following situations:
    • Older than 75 years.
    • Multiple comorbid conditions.
    • Elevated liver enzymes.
    • Changing thyroid status.
  • Dose to maintain international normalized ratio (INR) between 2 and 3.
Monitoring:
  • INR daily until in therapeutic range for 2 consecutive days.
  • Then two or three times weekly for 1 to 2 weeks.
  • Then less frequently but at least every 6 weeks.
Rivaroxaban (Xarelto): Factor Xa inhibitor. Apixaban (Eliquis): Factor Xa inhibitor.
  • Reduction of risk of stroke and systemic embolism in nonvalvular atrial fibrillation.
  • Prophylaxis of DVT following knee replacement surgery.
  • Treatment of DVT and PE.

Parenteral Anticoagulants

Heparin:
  • Binds with the antithrombin III.
  • Inactivates factors IXa, Xa, XIIa, XIII.
Pharmacokinetics:
  • Given IV or subcutaneously (SC).
  • Extensively protein-bound.
  • Metabolized by liver and renally eliminated.
Precautions and contraindications:
  • Pregnancy category C.
  • Avoid in advanced hepatic or renal disease.
  • Avoid in bleeding disorders or active bleeding.
Adverse drug reactions (ADRs):
  • May cause thrombocytopenia.
  • Life-threatening bleeding.
  • Pain at injection site (SC).
  • Antidote is protamine sulfate.
Drug interactions:
  • Cephalosporins and penicillins; Warfarin, antiplatelets and thrombolytics; Valproic acid.
Clinical use and dosing:
  • Given 2 hours pre-operatively.
  • Maintenance every 8 to 12 hours for 7 days after surgery.
  • Heparin is processed into smaller molecules → low molecular-weight heparins (LMWH).
  • Inactivates factor Xa.
Enoxaparin:
  • DVT or PE.
  • Given 2 hours before surgery.
Fondaparinux: Selective inhibitor of antithrombin III and factor Xa inhibitor.
  • DVT.
  • Hip fracture surgery or knee replacement.
Dalteparin:
  • Prevention of DVT after abdominal surgery or hip replacement.
Monitoring for Anticoagulants:
  • Activated partial thromboplastin time.
  • Platelet and hematocrit (Hct) every 2 to 3 days initially.
Patient Education for Anticoagulants:
  • Administration.
  • Warfarin dosing may vary day to day.