Coumadin - Indications & Dosage

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Intervals between subsequent PT/ INR determinations should be based upon the physician's judgment of the patient's reliability and response to COUMADIN 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. To ensure adequate control, it is recommended that additional PT tests are done when other warfarin products are interchanged with warfarin sodium tablets, USP, as well as whenever other medications are initiated, discontinued, or taken irregularly (see PRECAUTIONS).

Different thromboplastin reagents vary substantially in their sensitivity to sodium warfarin-induced effects on PT. To define the appropriate therapeutic regimen it is important to be familiar with the sensitivity of the thrombo-plastin reagent used in the laboratory and its relationship to the International Reference Preparation (IRP), a sen-sitive thromboplastin reagent prepared from human brain.

A system of standardizing the PT in oral anticoagulant control was introduced by the World Health Organization in 1983. It is based upon the determination of an International Normalized Ratio (INR) which provides a common basis for communication of PT results and interpretations of therapeutic ranges. The INR system of reporting is based on a logarithmic relationship between the PT ratios of the test and reference preparation. The INR is the PT ratio that would be obtained if the International Reference Preparation (IRP), which has an ISI of 1.0, was used to perform the test. Early clinical studies of oral anticoagulants, which formed the basis for recommended therapeutic ranges of 1.5 to 2.5 times control mean normal PT, used sensitive human brain thromboplastin. When using the less sen-sitive rabbit brain thromboplastins commonly employed in PT assays today, adjustments must be made to the tar-geted PT range that reflect this decrease in sensitivity.

The INR can be calculated as: INR = (observed PT ratio) ISI where the ISI (International Sensitivity Index) is the cor-rection factor in the equation that relates the PT ratio of the local reagent to the reference preparation and is a meas-ure of the sensitivity of a given thromboplastin to reduction of vitamin K-dependent coagulation factors; the lower the ISI, the more "sensitive" the reagent and the closer the derived INR will be to the observed PT ratio. 1