IJCS | Volume 32, Nº2, March/April 2019

DOI: 10.5935/2359-4802.20180091 110 ORIGINAL ARTICLE International Journal of Cardiovascular Sciences. 2019;32(2)110-117 Mailing Address: Christiane de Fátima Colet Rua São Francisco, 600/404. Postal Code: 98700-000, São Geraldo, Ijuí, RS - Brazil. E-mail: chriscolet@yahoo.com.br , christiane.colet@unijui.edu.br Drug Interactions and Adverse Events in a Cohort of Warfarin Users Attending Public Health Clinics Christiane de Fátima Cole t, T ania Alves Amado r, Isabela Heinec k Universidade Federal do Rio Grande do Sul, RS - Brazil Manuscript received on April 10, 2018, revised manuscript on August 09, 2018, accepted on August 17, 2018. Abstract Background: Warfarin is an oral anticoagulant involved in important interactions with foods and other drugs. Objectives: To evaluate the occurrence of adverse events reported by warfarin users and their relationship with drug interactions. Methods: This was an open cohort, prospective study conducted in an 18-month period with warfarin users attending public health clinics of the city of Ijuí, Brazil. Data were collected by means of interviews administered at patients’ home every month. Patients’ responses were confirmed by review of medical records when patients sought medical care. Data were analyzed by descriptive statistics. Potential drug interactions were evaluated in a database and vitamin K consumption was quantified using a validated method. Results: A total of 68 patients were followed-up; 63 completed the study and 5 died in the study period. Mean number of medications taken by the patients was 9.6 ± 4.5, and mean number of interactions involving warfarin was 2.91 ± 1.52. Most potential interactions increased the risk of bleeding, 61 of them severe interactions and 116 moderate interactions. Eighty-seven episodes of bleeding and 4 episodes of thrombosis were reported by a total of 37 and 4 patients, respectively. At the occurrence of these events, 56.5% of warfarin users were also taking omeprazole, 35.9% were taking simvastatin and 25.0% paracetamol. Most patients had a low vitamin K intake. Conclusions: A high frequency of potential interactions between warfarin and other drugs was detected, but a low intake of foods that could possibly affect the effects of warfarin was observed. Based on our results, it seems prudent to follow patients on warfarin therapy for drug-drug interactions, aiming to control adverse effects and to promote a safe and effective therapy. (Int J Cardiovasc Sci. 2019;32(2)110-117) Keywords: Anticoagulants/adverse effects; Warfarin; Pharmacovigilance; Drug Interactions; Drug Incompatibility; Omeprazole; Simvastatin; Acetaminophen; Vitamin K; Delivery Health Care/statistics & numeral data. Introduction Warfarin is one of the most used oral anticoagulants. According to the Food and Drug Administration, it is among the top ten drugs in terms of the risk of severe side effects. 1 Warfarin is characterized by a narrow therapeutic window, high interaction with other drugs and frequent bleeding. 2 The effect of warfarin may be either increased or decreased when combined with some drugs or foods. These interactions can be potentially harmful to patients and caused increased health-related costs, 3 which justifies the need to identify potential interactions involving warfarin that may lead to adverse effects. The risk for adverse events caused by drug interactions with warfarin increases with the number of drugs administered concomitantly, 4 whereas vitamin K-rich diets may decrease warfarin therapeutic effect. 5 The occurrence of adverse events may be prevented by monitoring of the therapy by health providers involved in its prescription, delivery and follow-up of anticoagulated patients. 6