![]() ![]() ĭeterminations of whole blood clotting and bleeding times are not effective measures for monitoring of COUMADIN therapy. Heparin, a common concomitant drug, increases the INR. Perform additional INR tests when other warfarin products are interchanged with COUMADIN, as well as whenever other medications are initiated, discontinued, or taken irregularly. The frequency of performing INR should be based on the clinical situation but generally acceptable intervals for INR determinations are 1 to 4 weeks. ![]() After stabilization, maintain dosing within the therapeutic range by performing periodic INRs. Determine the INR daily after the administration of the initial dose until INR results stabilize in the therapeutic range. Therefore, anticoagulation must be carefully monitored during COUMADIN therapy. Monitoring to Achieve Optimal AnticoagulationĬOUMADIN has a narrow therapeutic range (index), and its action may be affected by factors such as other drugs and dietary vitamin K. Other co-inherited VKORC1 variants may also be important determinants of warfarin dose. VKORC1–1639G>A (rs9923231) variant is used in this table. Table 1: Three Ranges of Expected Maintenance COUMADIN Daily Doses Based on CYP2C9 and VKORC1 Genotypes† † Ranges are derived from multiple published clinical studies. 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. If the patient’s CYP2C9 and/or VKORC1 genotype are known, consider these ranges in choosing the initial dose. Table 1 displays three ranges of expected maintenance COUMADIN doses observed in subgroups of patients having different combinations of CYP2C9 and VKORC1 gene variants. ĭosing Recommendations with Consideration of Genotype In general, anticoagulant therapy should be continued until the danger of thrombosis and embolism has passed. Individualize the duration of therapy for each patient. 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. Consider lower initial and maintenance doses for elderly and/or debilitated patients and in Asian patients. Modify this dose based on consideration of patient-specific clinical factors. Select the initial dose based on the expected maintenance dose, taking into account the above factors. Genetic factors (CYP2C9 and VKORC1 genotypes).Clinical factors including age, race, body weight, sex, concomitant medications, and comorbidities.Not all factors responsible for warfarin dose variability are known, and the initial dose is influenced by: The appropriate initial dosing of COUMADIN varies widely for different patients. 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.For patients with AF and mitral stenosis, long-term anticoagulation with warfarin is recommended.In patients with non-valvular AF that is persistent or paroxysmal and at an intermediate risk of ischemic stroke (i.e., 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.In patients with non-valvular AF that is persistent or paroxysmal and at high risk of stroke (i.e., 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.In patients with non-valvular AF, anticoagulate with warfarin to target INR of 2.5 (range, 2.0-3.0). ![]()
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