Generic Name

Warfarin

Mechanism

• Inhibits the vitamin K epoxide reductase complex‑1 (VKORC1), preventing regeneration of reduced vitamin K.
• Suppresses γ‑carboxylation of coagulation factors II, VII, IX, X, and proteins C & S, thereby impairing the catalytic activity of clotting enzymes.
• Decreases clotting activity by 25‑50 % within 24 h and by >75 % after 3–5 days, creating a therapeutic “anticoagulant window.”

Pharmacokinetics

• Absorption: Nearly complete (~90 %) oral uptake; peak plasma concentration in 1–3 h.
• Distribution: Widely distributed; highly protein‑bound (>99 %) to albumin and α‑1‑acid glycoprotein; large volume of distribution (~2 L/kg).
• Metabolism: Extensive hepatic metabolism via CYP2C9 (primary), CYP3A4, and CYP1A2. Genetic polymorphisms strongly influence dose requirements.
• Elimination: Metabolites excreted primarily by the kidneys; terminal half‑life ≈ 40 h (range 20–60 h); highly variable with a typical therapeutic window of 3–4 days.

Indications

• Therapeutic anticoagulation for:
• Non‑valvular atrial fibrillation (stroke prevention).
• Mechanical prosthetic heart valves (type‑specific dosing).
• Deep venous thrombosis (DVT) and pulmonary embolism (PE) therapeutic & prophylactic.
• Prevention of recurrent thrombosis post‑arterial or venous thrombosis.
• Mitral valve disease in patients undergoing surgery or with complications.

Contraindications

• Absolute contraindications:
• Active bleeding or imminent procedures requiring hemostasis.
• Severe hepatic dysfunction (Child‑Pugh C) or cholestatic jaundice.
• Pregnancy (Category X) – use is teratogenic in first trimester.
• Relative cautions:
• Uncontrolled hypertension.
• History of warfarin‑induced skin necrosis (rare genetic defects in protein C/S).
• Concomitant use of drugs heavily dependent on CYP2C9 (e.g., amiodarone, dapsone) without dose adjustment.
• Drug‑drug interactions: High‑risk with antibiotics (ceftriaxone, erythromycin), antifungals (ketoconazole, fluconazole), and many herbal supplements (ginkgo, garlic, St. John’s wort).

Dosing

• Initial loading dose: 5 mg PO once daily in most patients; however, dose may vary (e.g., 7.5–10 mg for prosthetic valves).
• Titration: Adjust by 1‑3 mg every 3–7 days based on International Normalized Ratio (INR) until target achieved (commonly INR 2.0–3.0; 2.5–3.5 for mechanical valves).
• Maintenance: 1–6 mg daily or 3–6 mg twice weekly. Dose individualized according to INR, genetics, age, weight, diet, comorbid conditions.
• Special populations:
• Elderly: Start with lower doses due to increased sensitivity.
• BMI >25 kg/m²: May need higher dose.
• Renal impairment: Dose adjustment minimal; monitor INR closely.
• Reversal: Vitamin K (1–10 mg IV) for major bleeding; FFP (10 mL/kg) or prothrombin complex concentrate (PC‑C) for rapid reversal.

Adverse Effects

Monitoring

• INR: Every 3–5 days during titration; thereafter weekly (stable) or as clinical need dictates.
• Complete Blood Count (CBC): Baseline, then 2–3 weeks after dose change to detect myelosuppression.
• Liver Function Tests (LFTs): Baseline and periodically for patients on concomitant hepatotoxic agents.
• Electrolytes & Renal Panel: Baseline; monitor in patients with renal disease or on interacting drugs.
• Drug Interaction Alerts: Regular medication review, especially before surgeries or after changes in diet (high vitamin K foods).

Clinical Pearls

• Vitamin K Diet Consistency: Even modest changes in green‑leaf vegetable intake can swing INR dramatically; educate patients to keep a consistent intake.
• CYP2C9 Genotyping: Identifies patients needing 30–70 % reduced dose—especially useful in diverse ethnic groups.
• Bridging Strategy: For high‑risk patients undergoing surgery, start with unfractionated heparin at a therapeutic dose, discontinue 12 h before procedure, resume warfarin 4–6 h afterward once hemostasis is achieved.
• Rapid Reversal Protocol: For life‑threatening hemorrhage, give 5 mg vitamin K IV and 4 units FFP, or 4‑factor PCC (two units) if available, to normalize INR in <20 min.
• Pregnancy‐Safe Alternatives: Low‑molecular‑weight heparin (LMWH) is preferred during pregnancy; avoid warfarin after the first trimester.
• Antibiotic Interactions: Cephalosporins (especially ceftriaxone) can induce warfarin metabolism, lowering INR; macrolides and fluoroquinolones potentiate warfarin, raising INR. Adjust dose accordingly.
• Monitoring Frequency: During rapid dose changes or drug interactions, check INR after 48–72 h; otherwise weekly for stable patients.

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• *This drug card is for educational purposes and should not replace detailed clinical guidelines or professional judgment.*