Coumadin - Clinical Pharmacology

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Elderly:

Patients 60 years or older appear to exhibit greater than expected prothrombin time (PT)/ International Normalized Ratio (INR) response to the anticoagulant effects of warfarin. The cause of the increased sensitivity to the anticoagulant effects of warfarin in this age group is unknown. This increased anticoagulant effect from war-farin may be due to a combination of pharmacokinetic and pharmacodynamic factors. Racemic warfarin clearance may be unchanged or reduced with increasing age.

Limited information suggests there is no difference in the clear-ance of S-warfarin in the elderly versus young subjects. However, there may be a slight decrease in the clearance of R-warfarin in the elderly as compared to the young. Therefore, as patient age increases, a lower dose of war-farin is usually required to produce a therapeutic level of anticoagulation.

Asians:

Asian patients may require lower initiation and maintenance doses of warfarin. One non-controlled study conducted in 151 Chinese outpatients reported a mean daily warfarin requirement of 3.3 ± 1.4 mg to achieve an INR of 2 to 2.5. These patients were stabilized on warfarin for various indications. Patient age was the most important determinant of warfarin requirement in Chinese patients with a progressively lower warfarin requirement with increasing age.

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:

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.