Interações medicamentosas da Varfarina em cardiopatas chagásicos e não chagásicos atendidos em ambulatórios do Hospital das Clínicas da UFMG

Abstract

Introduction: Drug interactions (DI) are an important cause of adverse events. They can increase drug related morbi-mortality and result in significant social and economic impact. Warfarin is a high risk drug due to its narrow therapeutic index, variability in dose-responseand potential for DI. The early identification of warfarin DI may help to prevent adverse events, especially hemorrhage. Objectives: To evaluate potential warfarin DI in different sources of drug information and to investigate the frequency of severe warfarin DI in Chagas and non-Chagas disease patients at the Hospital das Clínicas of the Universidade Federal de Minas Gerais (UFMG). Methods: The lists of warfarin interactions provided by three compendia (Drug Interaction Facts, Drug Interactions: Analysis and Management and DRUG-REAX), the World Health Organization (WHO) Model Formulary and the Marevan®package insert were all compared in terms of: cited substances, severity ratings and documentation levels. A cross-sectional study was carried out enrolling patients with heart diseases to evaluate warfarin DI and its frequency according to the sources. A kappa coefficient was used to calculate the agreement between the sources. Results: A total of537 interactions were listed. Only 13 (2.4%) were common to the five sources. Most critical interactions cited by the compendia were missing from the package insert. The global Fleiss kappa coefficient was -0.0080. Only two warfarin interactions were reported as critical coincidently by the three compendia and by the WHO. A total of 280 patients were studied (84 Chagas and 196 non-Chagas disease patients). Most patients were female (54.6%) with an average age of 56.8 (SD 13.1) years old. They showed no statistical differences in their sociodemographic characteristics. However, non-Chagas individualshad more comorbidities. The frequency of severe warfarin DI was variable among the sources resulting in a Fleiss kappa coefficient of 0.295. The frequency of severe warfarin DI showed disagreement with a wide variability between the sources when history of bleeding was assessed and Chagas and non-Chagas disease patients were compared.Conclusions: Poor agreement was found among five sources listing warfarin interactions. The package insert was the most incomplete source of drug information. The evaluation of warfarin DI in patients with heart diseases showed that the disagreement found in the compendia extends itself to the clinical practice.