Warfarin

Drug Information: Warfarin

Warfarin is a widely prescribed anticoagulant medication used to prevent and treat blood clots. It’s a vitamin K antagonist, meaning it interferes with the body’s ability to use vitamin K to produce clotting factors. Because it affects clotting, it requires careful monitoring via regular blood tests (INR) to ensure the dosage is within a therapeutic range, balancing clot prevention with the risk of bleeding. Warfarin is available in oral tablet form.

Category

Anticoagulant

Mechanism of Action

Warfarin acts as a vitamin K antagonist, interfering with the synthesis of vitamin K-dependent clotting factors II, VII, IX, and X, as well as the anticoagulant proteins C and S. Vitamin K is a crucial cofactor for the enzyme gamma-glutamyl carboxylase, which is responsible for the post-translational modification (gamma-carboxylation) of these clotting factors. This carboxylation is essential for the factors to bind calcium ions and interact with phospholipid surfaces, a necessary step for their participation in the coagulation cascade. Warfarin inhibits the vitamin K epoxide reductase (VKORC1) enzyme complex. This enzyme is responsible for regenerating the active form of vitamin K, vitamin K hydroquinone (KH2), from vitamin K epoxide (formed during the carboxylation reaction). By inhibiting VKORC1, warfarin reduces the availability of KH2, thereby decreasing the carboxylation of clotting factors. This leads to the production of non-functional or partially functional clotting factors that cannot effectively participate in the coagulation cascade, resulting in an anticoagulant effect. The full anticoagulant effect of warfarin is delayed because it only affects newly synthesized clotting factors. Pre-existing, functional clotting factors must be cleared from the circulation before the full therapeutic effect is achieved, typically taking several days.

Clinical Uses

Warfarin is clinically indicated for a variety of thromboembolic conditions. A primary use is in the prevention of stroke and systemic embolism in patients with atrial fibrillation (AFib). AFib, an irregular heart rhythm, increases the risk of blood clot formation in the heart, which can then travel to the brain and cause a stroke. Warfarin is also used to treat and prevent venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a blood clot that forms in a deep vein, typically in the leg, while PE occurs when a DVT breaks loose and travels to the lungs. Other uses include preventing blood clots in patients with mechanical heart valves, in those who have had a heart attack and are at risk of developing clots, and in certain hypercoagulable states. The use of Warfarin must be carefully considered alongside other anticoagulation options, and weighed against the risk of bleeding.

Dosage

Adults: The initial adult dose is typically 2-5 mg orally once daily. The dose is adjusted based on the International Normalized Ratio (INR) to achieve a target INR, often between 2.0 and 3.0 for most indications. The maintenance dose varies widely, ranging from 1 mg to 10 mg daily, depending on individual patient factors and INR response.

Pediatrics: Pediatric dosing is individualized based on weight and INR response. The typical starting dose ranges from 0.1-0.3 mg/kg/day orally, adjusted to maintain the target INR, which is typically between 2.0 and 3.0.

Route of Administration: Oral.

Indications

Common indications for Warfarin include:

• Atrial fibrillation (to prevent stroke)
• Venous thromboembolism (DVT and PE) treatment and prevention
• Mechanical heart valves (to prevent clot formation on the valve)
• Prevention of systemic embolism
• Hypercoagulable states (e.g., antiphospholipid syndrome)

Contraindications

Warfarin is contraindicated in the following situations:

• Pregnancy (especially the first trimester)
• Active bleeding
• Severe liver disease
• Uncontrolled hypertension
• Recent major surgery or trauma
• Known hypersensitivity to warfarin
• Patients with a high risk of falls or poor adherence to monitoring requirements

FAQ

1. What is Warfarin used for?
   Warfarin is used to prevent and treat blood clots, reducing the risk of stroke, pulmonary embolism, and deep vein thrombosis.
2. How does Warfarin work?
   Warfarin interferes with the body’s use of vitamin K to produce clotting factors, thereby slowing down the clotting process.
3. How often do I need blood tests when taking Warfarin?
   Regular blood tests (INR) are required to monitor the effectiveness of Warfarin and adjust the dosage accordingly. The frequency of testing is determined by your doctor, but is more frequent at the initiation of therapy and can be spaced further apart when INR is stable.
4. What are the common side effects of Warfarin?
   The most common side effect is bleeding. Other side effects can include nausea, vomiting, abdominal pain, and skin rash.
5. What should I do if I miss a dose of Warfarin?
   Contact your doctor or pharmacist for instructions. Do not double the next dose to make up for a missed one.
6. Can I take other medications with Warfarin?
   Many medications can interact with Warfarin, so it is crucial to inform your doctor about all medications you are taking, including over-the-counter drugs and herbal supplements.
7. What foods should I avoid while taking Warfarin?
   You don’t need to avoid any particular foods, but it’s important to maintain a consistent intake of vitamin K-rich foods (such as leafy green vegetables) to help stabilize your INR. Sudden changes in vitamin K intake can affect Warfarin’s effectiveness.
8. What should I do if I experience a minor cut or injury while on Warfarin?
   Apply direct pressure to the wound for an extended period. If bleeding is excessive or does not stop, seek medical attention immediately.