2 DOSAGE AND ADMINISTRATION Individualize dosing regimen for each patient, and adjust based on INR response. 2 ) Knowledge of genotype can inform initial dose selection. 3 ) Monitoring: Obtain daily INR determinations upon initiation until stable in the therapeutic range.
Obtain subsequent INR determinations every 1 to 4 weeks. 4 ) Review conversion instructions from other anticoagulants. 1 Individualized Dosing The dosage and administration of warfarin sodium tablets must be individualized for each patient according to the patient’s International Normalized Ratio (INR) response to the drug.
Adjust the dose based on the patient’s INR and the condition being treated. Consult the latest evidence-based clinical practice guidelines regarding the duration and intensity of anticoagulation for the indicated conditions. 2 Recommended Target INR Ranges and Durations for Individual Indications An INR of greater than 4 appears to provide no additional therapeutic benefit in most patients and is associated with a higher risk of bleeding.
5 (INR range, 2 to 3) for all treatment durations.
The duration of treatment is based on the indication as follows:
For patients with a DVT or PE secondary to a transient (reversible) risk factor, treatment with warfarin for 3 months is recommended. For patients with an unprovoked DVT or PE, treatment with warfarin is recommended for at least 3 months.
After 3 months of therapy, evaluate the risk-benefit ratio of long-term treatment for the individual patient. For patients with two episodes of unprovoked DVT or PE, long-term treatment with warfarin is recommended. For a patient receiving long-term anticoagulant treatment, periodically reassess the risk-benefit ratio of continuing such treatment in the individual patient.
5 (range, 2 to 3). , having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, or 2 of the following risk factors: age greater than 75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitus), long-term anticoagulation with warfarin is recommended.
, having 1 of the following risk factors: age greater than 75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitus), long-term anticoagulation with warfarin is recommended.
For patients with AF and mitral stenosis, long-term anticoagulation with warfarin is recommended. For patients with AF and prosthetic heart valves, long-term anticoagulation with warfarin is recommended; the target INR may be increased and aspirin added depending on valve type and position, and on patient factors.
5 (range, 2 to 3) is recommended. 5) is recommended. 5) is recommended. 5 (range, 2 to 3) for the first 3 months after valve insertion is recommended. 5 (range 2 to 3) is recommended. , those with a large anterior MI, those with significant heart failure, those with intracardiac thrombus visible on transthoracic echocardiography, those with AF, and those with a history of a thromboembolic event), therapy with combined moderate-intensity (INR, 2 to 3) warfarin plus low-dose aspirin (≤ 100 mg/day) for at least 3 months after the MI is recommended.
Recurrent Systemic Embolism and Other Indications Oral anticoagulation therapy with warfarin has not been fully evaluated by clinical trials in patients with valvular disease associated with AF, patients with mitral stenosis, and patients with recurrent systemic embolism of unknown etiology.
However, a moderate dose regimen (INR 2 to 3) may be used for these patients. 3 Initial and Maintenance Dosing The appropriate initial dosing of warfarin sodium tablets varies widely for different patients. 5 )] Select the initial dose based on the expected maintenance dose, taking into account the above factors.
Modify this dose based on consideration of patient-specific clinical factors. 3 )] . Routine use of loading doses is not recommended as this practice may increase hemorrhagic and other complications and does not offer more rapid protection against clot formation.
Individualize the duration of therapy for each patient. 2 )] . Dosing Recommendations without Consideration of Genotype If the patient’s CYP2C9 and VKORC1 genotypes are not known, the initial dose of warfarin sodium tablets is usually 2 to 5 mg once daily.
Determine each patient’s dosing needs by close monitoring of the INR response and consideration of the indication being treated. Typical maintenance doses are 2 to 10 mg once daily. 5 )] . If the patient’s CYP2C9 and/or VKORC1 genotype are known, consider these ranges in choosing the initial dose.
Patients with CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3 may require more prolonged time (> 2 to 4 weeks) to achieve maximum INR effect for a given dosage regimen than patients without these CYP variants. 5 to 2 mg † Ranges are derived from multiple published clinical studies.
VKORC1−1639G > A (rs9923231) variant is used in this table. Other co-inherited VKORC1 variants may also be important determinants of warfarin dose. 4 Monitoring to Achieve Optimal Anticoagulation Warfarin sodium tablets have a narrow therapeutic range (index), and their action may be affected by factors such as other drugs and dietary vitamin K.
Therefore, anticoagulation must be carefully monitored during warfarin sodium tablets therapy. Determine the INR daily after the administration of the initial dose until INR results stabilize in the therapeutic range. After stabilization, maintain dosing within the therapeutic range by performing periodic INRs.
The frequency of performing INR should be based on the clinical situation but generally acceptable intervals for INR determinations are 1 to 4 weeks. Perform additional INR tests when other warfarin products are interchanged with warfarin sodium tablets, as well as whenever other medications are initiated, discontinued, or taken irregularly.
8 ) and Drug Interactions ( 7 )] . Determinations of whole blood clotting and bleeding times are not effective measures for monitoring of warfarin sodium tablets therapy. 5 Renal Impairment No dosage adjustment is necessary for patients with renal failure.
6 )]. 6 Missed Dose The anticoagulant effect of warfarin sodium tablets persists beyond 24 hours. If a patient misses a dose of warfarin sodium tablets at the intended time of day, the patient should take the dose as soon as possible on the same day.
The patient should not double the dose the next day to make up for a missed dose. 7 Treatment During Dentistry and Surgery Some dental or surgical procedures may necessitate the interruption or change in the dose of warfarin sodium tablets therapy.
Consider the benefits and risks when discontinuing warfarin sodium tablets even for a short period of time. Determine the INR immediately prior to any dental or surgical procedure. In patients undergoing minimally invasive procedures who must be anticoagulated prior to, during, or immediately following these procedures, adjusting the dosage of warfarin sodium tablets to maintain the INR at the low end of the therapeutic range may safely allow for continued anticoagulation.
8 Conversion From Other Anticoagulants Heparin Since the full anticoagulant effect of warfarin sodium tablets is not achieved for several days, heparin is preferred for initial rapid anticoagulation. During initial therapy with warfarin sodium tablets, the interference with heparin anticoagulation is of minimal clinical significance.
Conversion to warfarin sodium tablets may begin concomitantly with heparin therapy or may be delayed 3 to 6 days. To ensure therapeutic anticoagulation, continue full dose heparin therapy and overlap warfarin sodium tablets therapy with heparin for 4 to 5 days and until warfarin sodium tablets has produced the desired therapeutic response as determined by INR, at which point heparin may be discontinued.
As heparin may affect the INR, patients receiving both heparin and warfarin sodium tablets should have INR monitoring at least: 5 hours after the last intravenous bolus dose of heparin, or 4 hours after cessation of a continuous intravenous infusion of heparin, or 24 hours after the last subcutaneous heparin injection.
Warfarin sodium tablets may increase the activated partial thromboplastin time (aPTT) test, even in the absence of heparin. A severe elevation (> 50 seconds) in aPTT with an INR in the desired range has been identified as an indication of increased risk of postoperative hemorrhage.
Other Anticoagulants Consult the labeling of other anticoagulants for instructions on conversion to warfarin sodium tablets.