Warfarin Personalized Dosage: Re-compounding for a More Suitable Therapy and Better Compliance

Warfarin is still the most prescribed oral anticoagulant prescribed for the prophylaxis and treatment of thromboembolic events such as stroke, heart attack, embolism, and deep vein thrombosis. It is administered orally in the form of sodium salt as a tablet with a typical strength of 5 mg. The molecule has a narrow therapeutic index. As a consequence, the dosage must be individualized for each patient based on the patient response in terms of time of coagulation. Thus, warfarin represents an example of a drug whose dose needs to be tailored to individual requirements that are often changing and, therefore, constitute a paramount illustration of personalized medicine. The aim of the present work was to investigate to what extent the manual division of a warfarin tablet by the patient represents an issue in terms of dose accuracy and precision. A second goal was to demonstrate that possible problems stemming from the manual division of the warfarin tablet could be overcome by compounding a solid dosage form (e.g., a capsule) starting from the commercially available warfarin product. The results of the present study put into evidence the great inhomogeneity and discrepancy from the target dose obtained when commercially available warfarin tablets are manually divided in four parts. This represents a potential source of inefficacy of the anticoagulant activity, with increased risk of either bleeding or thromboembolic events. The proposed solution is effective and yet simple and economically affordable, in particular considering the cost of the possible hospitalizations related to therapy failure.