What is the dosing scheme for Warfarin (Coumadin) and how often should International Normalized Ratio (INR) be monitored?

From the Guidelines

Warfarin dosing should typically begin at 4 to 5 mg daily, with adjustments based on INR monitoring, and the frequency of INR testing should be daily until the therapeutic range has been reached and sustained for 2 consecutive days, then 2 or 3 times weekly for 1 to 2 weeks, and eventually reduced to intervals as long as 4 weeks once the INR becomes stable. The target INR range is usually 2.0-3.0, though patients with mechanical heart valves may require a higher range of 2.5-3.5 1. Initial INR monitoring should be frequent, and dose adjustments should be made gradually, typically changing by 5-20% of the weekly dose. Factors affecting warfarin sensitivity include age, body weight, diet (especially vitamin K intake), concurrent medications, alcohol consumption, and certain medical conditions 1. Patients should maintain consistent vitamin K intake, avoid excessive alcohol, and inform healthcare providers about all medications including over-the-counter products and supplements. Some key points to consider when managing warfarin therapy include:

• Starting doses of 4 to 5 mg/d should be used in patients sensitive to warfarin, including the elderly, and in those at increased risk of bleeding 1
• The safety and effectiveness of warfarin therapy depends critically on maintaining the INR within the therapeutic range, as on-treatment analysis of the primary prevention trials in atrial fibrillation found that a disproportionate number of thromboembolic and bleeding events occurred when the PT ratio was outside the therapeutic range 1
• Long-term management is challenging for patients who have experienced bleeding during warfarin anticoagulation yet require thromboembolic prophylaxis, and in such cases, a target INR of 2.0 to 2.5 may be sensible for patients with mechanical prosthetic heart valves and persistent risk of bleeding during anticoagulation in the therapeutic range 1.

From the FDA Drug Label

The dosing of warfarin sodium tablets must be individualized according to patient’s sensitivity to the drug as indicated by the PT/INR It is recommended that warfarin sodium tablets therapy be initiated with a dose of 2 to 5 mg per day with dosage adjustments based on the results of PT/INR determinations. Most patients are satisfactorily maintained at a dose of 2 to 10 mg daily. The PT should be determined daily after the administration of the initial dose until PT/INR results stabilize in the therapeutic range. Intervals between subsequent PT/INR determinations should be based upon the physician’s judgment of the patient’s reliability and response to warfarin sodium tablets in order to maintain the individual within the therapeutic range Acceptable intervals for PT/INR determinations are normally within the range of one to four weeks after a stable dosage has been determined

The warfarin dose scheme typically starts with an initial dose of 2 to 5 mg per day, with adjustments based on PT/INR results. The maintenance dose is usually between 2 to 10 mg daily.

• Monitoring of INR should be done:
  • Daily after the initial dose until results stabilize
  • At intervals of 1 to 4 weeks after a stable dosage has been determined
  • More frequently when other medications are initiated, discontinued, or taken irregularly
  • Before any dental or surgical procedure 2

From the Research

Warfarin Dosing Scheme

• The initial dose of warfarin should be 5-mg (or 2 to 4 mg in the very elderly) to avoid loading doses that can raise the International Normalized Ratio (INR) excessively 3
• Adjusting a steady-state warfarin dose depends on the measured INR values and clinical factors, with most changes altering the total weekly dose by 5% to 20% 3
• A daily fixed 2.5-mg warfarin dose can be used as an alternative to a 5-mg loading dose, especially in patients after heart valve replacement, to reduce excessive anticoagulation and achieve a more regular therapeutic target 4

Monitoring of INR

• The INR should be monitored frequently (e.g., 2 to 4 times per week) immediately after initiation of warfarin, and the interval between INR tests can be lengthened gradually (up to a maximum of 4 to 6 weeks) in patients with stable INR values 3
• For patients with stable INRs, the frequency of INR testing can be extended from every 4 weeks to up to 12 weeks 5
• Daily monitoring of the INR is still recommended in certain situations, such as in patients after heart valve replacement 4

Management of Elevated INR

• Patients with an elevated INR will need more frequent testing and may also require vitamin K1 3
• A nonbleeding patient with an INR of 9 can be given low-dose vitamin K1 (e.g., 2.5 mg phytonadione, by mouth) 3
• Patients who have an excessive INR with clinically important bleeding require clotting factors (e.g., fresh-frozen plasma) as well as vitamin K1 3