Drug Name
Generic Name
Warfarin
Brand Name(s)
- Pakistan: Marevan
- India: Coumadin
- US: Coumadin, Jantoven
- UK: Warfarin Sodium
Pharmacological Class
Class
Anticoagulant
Subclass
Vitamin K antagonist
Mechanism of Action
Warfarin inhibits the synthesis of vitamin K-dependent clotting factors II, VII, IX, and X, as well as the anticoagulant proteins C and S. This inhibition prevents the formation of blood clots.
Indications
Primary Indications
Prevention and treatment of venous thrombosis, pulmonary embolism, thromboembolic complications associated with atrial fibrillation, and/or cardiac valve replacement.
Off-label Uses
Prevention of recurrent transient ischemic attacks (TIAs) and myocardial infarction (MI).
Dosage and Administration
Standard Dosage
The dosage of Warfarin is individualized based on the patient's INR (International Normalized Ratio) response. Typical starting dose ranges from 2 to 5 mg daily.
Route of Administration
Oral
Special Populations
- Pediatric: Adjusted based on INR response.
- Geriatric: Often requires lower dosages due to increased sensitivity.
Pharmacokinetics
Absorption
Warfarin is rapidly absorbed from the gastrointestinal tract.
Distribution
Highly protein-bound (about 99%) to plasma proteins, mainly albumin.
Metabolism
Metabolized by hepatic cytochrome P450 enzymes, primarily CYP2C9, CYP1A2, and CYP3A4.
Excretion
Excreted in urine (92% as metabolites, 8% as unchanged drug).
Half-life
Approximately 20 to 60 hours, with an average of about 40 hours.
Contraindications
Warfarin is contraindicated in patients with hypersensitivity to the drug, hemorrhagic tendencies, recent or planned surgery of the central nervous system, eye or traumatic surgery, bleeding tendencies associated with active ulceration or overt bleeding, severe uncontrolled hypertension, pericarditis or pericardial effusion, bacterial endocarditis, and in pregnant women except in women with mechanical heart valves who are at high risk of thromboembolism.
Warnings and Precautions
Regular monitoring of INR is essential to minimize the risk of bleeding complications. Caution is advised in patients with liver disease, kidney disease, hypertension, or any condition that predisposes to bleeding. Patients should be educated about dietary vitamin K interactions, and the importance of adhering to prescribed dosing schedules.
Side Effects
Common Side Effects
Bleeding, nausea, vomiting, diarrhea, abdominal pain.
Serious Side Effects
Severe bleeding, including intracranial, gastrointestinal, and retroperitoneal hemorrhage; purple toe syndrome; skin necrosis.
Drug Interactions
Major Interactions
Amiodarone, antibiotics (e.g., ciprofloxacin, erythromycin), antifungal agents (e.g., fluconazole), NSAIDs, antiplatelet agents.
Moderate Interactions
Barbiturates, carbamazepine, rifampin, vitamin K.
Minor Interactions
Acetaminophen (in large doses), dietary vitamin K, cranberry juice.
Pregnancy and Lactation
Pregnancy Category
Category X (contraindicated in pregnancy due to risk of fetal hemorrhage and teratogenicity).
Breastfeeding Considerations
Warfarin is considered compatible with breastfeeding; however, monitoring of the infant for bruising or bleeding is advised.
Patient Counseling Information
Patients should be informed about the importance of regular INR monitoring, recognizing signs of bleeding, dietary considerations regarding vitamin K intake, and the potential for drug-drug and drug-food interactions. Patients should also be advised to avoid activities with a high risk of injury and to report any unusual bleeding or bruising to their healthcare provider immediately.