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Renal Dysfunction: Renal clearance is considered to be a minor determinant of anticoagulant response to war-farin. No dosage adjustment is necessary for patients with renal failure. Hepatic Dysfunction: Text Continues Below
Hepatic dysfunction can potentiate the response to warfarin through impaired synthesis of clotting factors and decreased metabolism of warfarin. The administration of COUMADIN (Warfarin Sodium) via the intravenous (IV) route should provide the patient with the same concentration of an equal oral dose, but maximum plasma concentration will be reached earlier. However, the full anticoagulant effect of a dose of warfarin may not be achieved until 72-96 hours after dosing, indicating that the administration of IV COUMADIN should not provide any increased biological effect or earlier onset of action. Clinical Trials Atrial Fibrillation (AF): In five prospective randomized controlled clinical trials involving 3711 patients with non-rheumatic AF, warfarin significantly reduced the risk of systemic thromboembolism including stroke (See Table 1). The risk reduction ranged from 60% to 86% in all except one trial (CAFA: 45%) which stopped early due to pub-lished positive results from two of these trials. The incidence of major bleeding in these trials ranged from 0.6 to 2.7% (See Table 1). Meta-analysis findings of these studies revealed that the effects of warfarin in reducing throm-boembolic events including stroke were similar at either moderately high INR (2.0-4.5) or low INR (1.4-3.0). There was a significant reduction in minor bleeds at the low INR. Similar data from clinical studies in valvular atrial fibrillation patients are not available. TABLE 1. CLINICAL STUDIES OF WARFARIN IN NON-RHEUMATIC AF PATIENTS*
Study n Thromboembolism % Major Bleeding
Warfarin-Warfarin-Treated Control PT %Risk Treated Control
Patients Patients Ratio INR Reduction p-value Patients Patients
AFASAK 335 336 1.5-2.0 2.8-4.2 60 0.027 0.6 0.0
SPAF 210 211 1.3-1.8 2.0-4.5 67 0.01 1.9 1.9
BAATAF 212 208 1.2-1.5 1.5-2.7 86 <0.05 0.9 0.5
CAFA 187 191 1.3-1.6 2.0-3.0 45 0.25 2.7 0.5
SPINAF 260 265 1.2-1.5 1.4-2.8 79 0.001 2.3 1.5 Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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