Warfarin sodium is a highly effective remedy for the prevention of thromboembolism in a wide variety of cardiovascular conditions.

Warfarin sodium is a highly effective remedy for the prevention of thromboembolism in a wide variety of cardiovascular conditions. Marked individual variability in the answer of the hemostatic system and the potential for significant interaction with other medicines mandates careful and regular monitoring of patients who receive warfarin. In the past decade, several clinical trials have demonstrated unequivocally the efficacy of warfarin for one as well as the other the primary and secondary prevention of misfortune in patients math atrial fibrillation.[1-8] In view of the high prevalence of atrial fibrillation in the somewhat old population (estimated to be 1 to 2% of bodys of [is greater than] 70 years of age), the plash of patients who are potential warfarin candidates has the couple grown and aged.

Despite the proven efficacy of warfarin in clinical trials, several observational studies have shown that many physicians are reluctant to give anticoagulants to patients with atrial fibrillation because of be of importance tos perceived or real, that the potential for major bleeding outweighs the risks of knock prevention.[9-15] The data generated from clinical trials clearly indicate that the benefits of embolic thump prevention outweigh the risks of major or fatal bleeding according to approximately 20 to 1,[16] even now valid concerns have been raised about the applicability of controll trials to clinical practice.[17] similar concerns revolve around, among other issues, the belief that patients in clinical trials received tighter anticoagulation bridle than would normally be obtained and that they constituted a small subgroup of patients characterized by way of reliability and, potentially, a gentle bleeding risk. Indeed, review of the atrial fibrillation trials that published information forward the percentage of screened patients who inscribeed the trial indicates that all nevertheless the AFASAK trial recruited les than 10% Although there were well adapted reasons for many patients not to be enlisted (such as concomitant conditions that required warfarin therapy), a significant number of the nonenrolled patients were trial candidates, and this depressed percentage reinforces the notion of the potential difference between patients seen in clinical practice and those in the trials.

Despite evidence that many warfarin-eligible patients do not receive anticoagulation, a review of the studies that have addressed this issue[9-15] does indicate that acceptability of warfarin therapy for pat prevention is increasing, with a higher percentage of patients receiving warfarin in late 1990 take a view ofs than in those performed in the earlier part of the decade. Certainly increased awareness of the efficacy of warfarin must have played a part but this decade has also seen the midespread introduction in the United States of the international normalized ratio (INR) to monitor prothrombin times[18] (thereby reducing a tremendous variability in the station of anticoagulation that results from the use of thromboplastins with different sensitivity) and a greater reliance forward anticoagulation clinics rather than individual practitioner curb of warfarin therapy.[19] Both of these innovations have been shown to eventuate in improved anticoagulation control and a decreased incidence of major (but not necessarily minor) bleeding.[20]

Any physician or encourage who has been responsible for the have the direction of of warfarin therapy recognizes the many vagaries of this put drugs into including interpatient variability of dose, interaction with many other put drugs intos and fluctuations in the INR associated with intercurrent illnesses, in the same state [i]or[/i] condition as an exacerbation of congestive heart failure. The nonlinear pharmacodynamics of warfarin require cautious dosage adjustment to maintain patients within the narrow range of INR wherein bleeding is minimized and antithrombotic result is maximized.[21,22] This demands not single great care on the part of the provider, yet also reliance on a mix with drugs formulation that is consistently within a surpassingly narrow range of bioavailability. In 1980 the unannounced substitution by dint of a hospital pharmacy amorphous warfarin sodium for crystalline warfarin sodium (Coumadin; Dupont Pharma; Wilmington, DE) in a cost-saving attempt flowed in loss of anticoagulation repress in a high proportion of patients monitored in the hospital's anticoagulation clinic.[23] The resultant increase in the number of patient visits necessitated by means of this substitution resulted in an increased charge of patient care and in risk of significant bleeding. Amorphous warfarin was subsequently withdrawn from the US market, and crystalline warfarin sodium, produc from a single manufacturer under the brand name Coumadin, has remained the no other than formulation of warfarin available until now.

lately generic crystalline warfarin sodium has been approved through the US Food and remedy Administration (FDA) as a therapeutically equivalent physic to Coumadin. Therapeutic equivalence requires not simply that the drug is a pharmaceutical equivalent (ie, has identical active ingredients with identical nerve and quality) but also that criteria for bioequivalence are met Bioequivalence testing is usually determined in a small number of normal tenders and the FDA permits the therapeutically "equivalent" put drugs into to differ from the pioneer medicine by a ratio and volume of absorption between -20 and +25%[24] This range may be clinically acceptable for in the same state [i]or[/i] condition drugs as antibiotics or flat antiarrhythmic agents, for which the therapeutic range is wide and merely roughly correlates with efficacy, still is of particular concern when like drugs as warfarin math a narrow therapeutic range[7,25-28] are discussed. The potential variation in bioavailability among different brands of' warfarin may cause significant enigmas because minor dose changes in susceptible patients, of that kind as the elderly, can deduction in clinically significant and potentially life-threatening deviations in the INR.

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