Background Patients’ preferences, needs and desires are important when discussing treatment. In consultations between patients with atrial fibrillation (AF) and health professionals, knowledge, understanding and insight about communication patterns are of vital importance for strengthening patient involvement in decision-making about their care and treatment. Aim The general aim of this thesis was to describe communication patterns in consultations between patients with AF and health professionals. Specific aims (1) To describe (i) the topics patients with AF and their nurses and physicians discuss; (ii) the use of discursive space in consultations between these participants; and (iii) the frequencies with which patients and nurses/physicians introduce the identified topics. (2) To describe the types of patient resistance to accepting treatment with warfarin and how cardiologists respond to such resistance. Methods An inductive design was used. In study I, the sample consisted of 23 consultations between patients with AF (13 women and 10 men) and health professionals (5 women and 5 men) who were employed in six different cardiologic outpatient clinics. Content analysis was used to obtain a description of topics discussed. The patterns of dominance for the various topics and participant were explored from the framework of an analysis of dominance (I). In study II, the sample consisted of 11 consultations between patients with AF (7 women and 4 men) and cardiologists (2 women and 3 men). Conversation analysis was used to describe interactions concerning resistance to treatment with warfarin. Findings Study I. Four topics were introduced by both nurses and physicians during the consultations. These were “pathophysiology”, “treatment”, “diagnostic procedures”, and “activity”. In the nurse–patient consultations an additional topic, “routines related to the physician’s responsibilities”, emerged. With respect to the number of words and turns, the distribution of the discourse space was almost equal between nurses and patients, and unequal between physicians and patients. The patients were the dominant initiators of the topic “activity”, which refers to adaptation of activities in daily life in relation to AF. Study II. There were four types of patient resistance to accepting treatment with warfarin. These included “Giving reasons for their resistance”, “Suggesting other treatment options”, “Stating treatment preferences” and “Questioning or challenging the cardiologist’s treatment recommendations”. The cardiologists’ responses to the patients’ resistance included “Repeating the treatment recommendation”, “Negotiation with the patient”, “Providing additional information about the recommended treatment” and “Extending their explanation of the purpose of the treatment”. Conclusions The medical-driven agenda dominated over the patient-driven agenda in consultations between health care professionals and patients with AF. During conversations in consultations with nurses, the patients initiated discussion of living with AF and were more talkative than they were with physicians. An awareness of types of patient resistance to treatment would enable cardiologists to consider patients’ experience-based views about their treatment;

In the first part of this thesis, the construction of the novel bifunctional proline-(1R,2R)-2-aminoDMAP organocatalyst backbone is described. Target compound has both Lewis base and Br&oslash / nsted acid catalaphoric sites. The Lewis base site is synthesized via selective mono-N-pyridilization of trans-(1R,2R)-cyclohexane-1,2-diamine by Cu catalysis and Br&oslash / nsted acid site is subsequently introduced by anchoring L-proline unit. In the second part, catalytic activities of organocatalysts are tested in asymmetric Michael addition reaction between a cyclic 1,3-dicarbonyl compound 4-hydroxycoumarin and various &alpha / ,&beta / -unsaturated ketones to afford optically active warfarin as anticoagulants, in one step. Reaction parameters such as solvent, temperature, equivalency, and cocatalyst were screened. Enantiomeric excess value (ee) up to 72% is attained.

Contexte: Bien que plusieurs algorithmes pharmacogénétiques de prédiction de doses de warfarine aient été publiés, peu d’études ont comparé la validité de ces algorithmes en pratique clinique réelle. Objectif: Évaluer trois algorithmes pharmacogénomiques dans une population de patients qui initient un traitement à la warfarine et qui souffrent de fibrillation auriculaire ou de problèmes de valves cardiaques. Analyser la performance des algorithmes de Gage et al., de Michaud et al. ainsi que de l’IWPC quant à la prédiction de la dose de warfarine permettant d’atteindre l’INR thérapeutique. Méthodes: Un devis de cohorte rétrospectif fut utilisé afin d’évaluer la validité des algorithmes chez 605 patients ayant débuté une thérapie de warfarine à l’Institut de Cardiologie de Montréal. Le coefficient de corrélation de Pearson ainsi que l’erreur absolue moyenne ont été utilisés pour évaluer la précision des algorithmes. L’exactitude clinique des prédictions de doses fut évaluée en calculant le nombre de patients pour qui la dose prédite était sous-estimée, idéalement estimée ou surestimée. Enfin, la régression linéaire multiple a été utilisée pour évaluer la validité d’un modèle de prédiction de doses de warfarine obtenu en ajoutant de nouvelles covariables. Résultats : L’algorithme de Gage a obtenu la proportion de variation expliquée la plus élevée (R2 ajusté = 44 %) ainsi que la plus faible erreur absolue moyenne (MAE = 1.41 ± 0.06). De plus, la comparaison des proportions de patients ayant une dose prédite à moins de 20 % de la dose observée a confirmé que l’algorithme de Gage était également le plus performant. Conclusion : Le modèle publié par Gage en 2008 est l’algorithme pharmacogénétique le plus exact dans notre population pour prédire des doses thérapeutiques de warfarine. / Background: Although numerous genotype-based warfarin dosing algorithms have been published, there is little data comparing the predictive ability of these algorithms in real clinical practice. Objectives: Our goal was to evaluate the performance of pharmacogenetic algorithms in an unselected patient population initiating warfarin treatment for atrial fibrillation or valve disease in a real-world clinical setting. The principal objective of the analysis was to determine if Gage’s, Michaud’s, and IWPC algorithms could predict the dose achieving the therapeutic International normalized ratio (INR). Methods: Data from a retrospective cohort study of 605 patients initiating warfarin therapy at the Montreal Heart Institute was used. We compared the dose predicted by the algorithms to the dose achieving the therapeutic INR. Pearson’s correlation coefficient and mean absolute error (MAE) were used to evaluate the predictive accuracy of the algorithms. Clinical accuracy of the predictions was assessed by computing the proportion of patients in which the predicted dose was under-estimated, ideally estimated, or overestimated. Finally, we used multiple linear regression analysis to evaluate the accuracy of a predictive model obtained by adding additional covariables in predicting therapeutic warfarin doses. Results: The proportion of variation explained (adjusted R2) was the highest for Gage’s algorithm (R2 = 44 %) and the mean absolute error was the smallest for the predictions made by Gage’s algorithm (MAE = 1.41 ± 0.06). Moreover, when we compared the proportion of patients whose predicted doses are within ± 20 % of the observed stable dose, Gage’s algorithm also performed the best overall. Conclusion: The algorithm published by Gage et al. in 2008 is the most accurate pharmacogenetically based equation in predicting therapeutic warfarin dose in our study population.

Background: Vitamin-K antagonists (VKA) are a class of oral anticoagulant medications used to prevent blood clots. The anticoagulant intensity of VKAs is measured with a blood test known as the International Normalized Ratio (INR). Traditionally, international guidelines have recommended INR tests every 4 weeks for all patients. However, adherence to these guidelines has never been investigated in real world settings. The objectives of this study were to describe adherence to INR testing in Saskatchewan among patients receiving VKA medications, and to identify predictors of optimal adherence. Methods: This was a retrospective cohort study of VKA users in Saskatchewan captured in the administrative data between 2003 and 2010. Physician claims for anticoagulation monitoring were used as a proxy for INR testing. Adherence to INR testing was measured using the Continuous, Multiple-Interval Measure of Medication Gaps (CMG). Individuals were considered adherent if adherence by the CMG was at least 80%. Hierarchical (random effects) logistic regression models were developed to identify important predictors of optimal INR monitoring. Individual physician identification was considered a random effect in these models. The dependent variable was the achievement of optimal adherence, defined as ≥80% adherence to the 4-week test interval. Results: Among 17,388 VKA users, 42% resided in rural areas and virtually all (99%) were monitored by a general practitioner. During a median follow-up of 514 days, 50% of patients exhibited at least 74% adherence to INR testing if a 4-week interval was used as the reference standard. However, the estimated median adherence increased dramatically to 98% when the benchmark for optimal testing was lengthened to every 12 weeks. The most prominent risk factors for poor adherence to INR monitoring appeared to be rural residence (rural vs. urban OR 0.55, 95% CI 0.47-0.64 among subjects age ≥75 years) and duration of VKA therapy (≥731 vs. 35-90 days OR 0.04, 95% CI 0.03-0.05). Discussion: Adherence to INR testing appeared to be acceptable for most VKA-treated patients in Saskatchewan. However, this data indicated that adherence might be more problematic in the subgroup of rural residents. Possible explanations include reduced access to testing facilities or the shortage of physicians in rural areas. Further research is required to understand if poor access is the underlying cause of non-adherence to INR testing in the rural population.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Washington, 2008. / Vita. Includes bibliographical references (leaves 186-207).

Orientador: Antônio José Maria Cataneo / Resumo: Introdução: O risco de sangramento em cirurgias realizadas na vigência de antitrombóticos preocupa o cirurgião, em contrapartida, a suspensão do agente antitrombótico aumenta o risco de trombose. Esse dilema levou a realização desta revisão. Objetivo: avaliar, por meio de revisão sistemática e metanálise, se há ou não necessidade de suspender medicamentos antitrombóticos orais (varfarina, fluindiona, acenocumarol, AAS e clopidogrel) para a realização de procedimentos eletivos de cirurgia do punho e da mão. Métodos: revisão sistemática de estudos experimentais ou observacionais que tenham avaliado cirurgias de mão e punho na vigência do agente antitrombótico. Foram pesquisadas as bases de dados LILACS, Pubmed, Embase, Cochrane e Scopus, sendo selecionados series com cinco ou mais cirurgias . Os desfechos avaliados foram: complicações graves (necessidade de tratamento cirúrgico) e leves (sem necessidade de tratamento cirúrgico). Resultados : foram selecionados 10 estudos observacionais para análise qualitativa envolvendo 2971 cirurgias. Seis desses estudos foram selecionados para análise quantitativa, envolvendo 319 cirurgias do punho e da mão realizadas na vigência de varfarina, fluindiona, acenocumarol, AAS e clopidogrel e 629 cirurgias realizadas em pacientes sem uso dos antitrombóticos. O risco de complicações leves foi maior nos pacientes que estavam recebendo antitrombóticos ( RR 1,55, IC 95% 1,02 a 2,35; I 2 = 23%, 948 cirurgias), e o risco de complicações graves foi sem... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction : The risks of bleeding in surgeries performed during the antithrombotic period are of concern to the surgeon, and on the other hand, the suspension of the antithrombotic agent increases the risk of thrombosis. This dilemma led to this review. Objective: to evaluate, through a systematic review, whether or not there is a need to suspend antithrombotic drugs (warfarin, fluindione, acenocumarol, ASA and clopidogrel) to perform elective procedures for wrist and hand surgery. Methods: systematic review of experimental or observational studies that have evaluated hand and wrist surgeries during the antithrombotic agent. The databases LILACS, Pubmed, Embase, Cochrane and Scopus were searched, being selected series with five or more surgeries. The outcomes evaluated were: severe complications (need for surgical treatment) and mild complications (no need for surgical treatment). Results: 10 observational studies were selected for qualitative analysis involving 2971 surgeries. Six of these studies were selected for quantitative analysis, involving 319 wrist and hand surgeries performed during warfarin, fluindione, acenocumarol, ASA and clopidogrel and 629 surgeries performed in patients without antithrombotic drugs. The risk of mild complications was greater in patients receiving antithrombotic drugs (RR 1.55, 95% CI 1.02 to 2.35, I 2 = 23%, 948 surgeries), and the risk of severe complications was similar in both groups (RR 1.83, 95% CI 0.32 to 10.29, I 2 = 0%, 948 surger... (Complete abstract click electronic access below) / Mestre

Submitted by FRANCISCO SIMOES DEIENNO (frandeienno@hotmail.com) on 2018-08-14T12:57:37Z No. of bitstreams: 1 Tese Final para Repositorio.pdf: 614767 bytes, checksum: 0f22aeef2c688aa8f97eb3c2d7bc5223 (MD5) / Approved for entry into archive by Sulamita Selma C Colnago null (sulamita@btu.unesp.br) on 2018-08-14T17:14:35Z (GMT) No. of bitstreams: 1 deienno_fs_me_bot.pdf: 614767 bytes, checksum: 0f22aeef2c688aa8f97eb3c2d7bc5223 (MD5) / Made available in DSpace on 2018-08-14T17:14:35Z (GMT). No. of bitstreams: 1 deienno_fs_me_bot.pdf: 614767 bytes, checksum: 0f22aeef2c688aa8f97eb3c2d7bc5223 (MD5) Previous issue date: 2018-07-19 / Introdução: O risco de sangramento em cirurgias realizadas na vigência de antitrombóticos preocupa o cirurgião, em contrapartida, a suspensão do agente antitrombótico aumenta o risco de trombose. Esse dilema levou a realização desta revisão. Objetivo: avaliar, por meio de revisão sistemática e metanálise, se há ou não necessidade de suspender medicamentos antitrombóticos orais (varfarina, fluindiona, acenocumarol, AAS e clopidogrel) para a realização de procedimentos eletivos de cirurgia do punho e da mão. Métodos: revisão sistemática de estudos experimentais ou observacionais que tenham avaliado cirurgias de mão e punho na vigência do agente antitrombótico. Foram pesquisadas as bases de dados LILACS, Pubmed, Embase, Cochrane e Scopus, sendo selecionados series com cinco ou mais cirurgias . Os desfechos avaliados foram: complicações graves (necessidade de tratamento cirúrgico) e leves (sem necessidade de tratamento cirúrgico). Resultados : foram selecionados 10 estudos observacionais para análise qualitativa envolvendo 2971 cirurgias. Seis desses estudos foram selecionados para análise quantitativa, envolvendo 319 cirurgias do punho e da mão realizadas na vigência de varfarina, fluindiona, acenocumarol, AAS e clopidogrel e 629 cirurgias realizadas em pacientes sem uso dos antitrombóticos. O risco de complicações leves foi maior nos pacientes que estavam recebendo antitrombóticos ( RR 1,55, IC 95% 1,02 a 2,35; I 2 = 23%, 948 cirurgias), e o risco de complicações graves foi semelhante nos dois grupos (RR 1,83, IC 95% 0,32 a 10,29; I 2 = 0%, 948 cirurgias). Conclusões: Pacientes em uso de anticoagulantes orais ou antiplaquetários orais tem um risco maior de desenvolver complicações leves, isto é aquelas que não necessitam de reintervenção cirúrgica , quando submetidos a cirurgias do punho e da mão na vigência de tratamento antitrombótico. / Introduction : The risks of bleeding in surgeries performed during the antithrombotic period are of concern to the surgeon, and on the other hand, the suspension of the antithrombotic agent increases the risk of thrombosis. This dilemma led to this review. Objective: to evaluate, through a systematic review, whether or not there is a need to suspend antithrombotic drugs (warfarin, fluindione, acenocumarol, ASA and clopidogrel) to perform elective procedures for wrist and hand surgery. Methods: systematic review of experimental or observational studies that have evaluated hand and wrist surgeries during the antithrombotic agent. The databases LILACS, Pubmed, Embase, Cochrane and Scopus were searched, being selected series with five or more surgeries. The outcomes evaluated were: severe complications (need for surgical treatment) and mild complications (no need for surgical treatment). Results: 10 observational studies were selected for qualitative analysis involving 2971 surgeries. Six of these studies were selected for quantitative analysis, involving 319 wrist and hand surgeries performed during warfarin, fluindione, acenocumarol, ASA and clopidogrel and 629 surgeries performed in patients without antithrombotic drugs. The risk of mild complications was greater in patients receiving antithrombotic drugs (RR 1.55, 95% CI 1.02 to 2.35, I 2 = 23%, 948 surgeries), and the risk of severe complications was similar in both groups (RR 1.83, 95% CI 0.32 to 10.29, I 2 = 0%, 948 surgeries). Conclusions: Patients taking oral anticoagulants or oral antiplatelet agents may be at increased risk of developing mild complications , that is, those that do not require surgical reintervention, when undergoing hand and wrist surgeries during antithrombotic treatment

A anticoagulação inadequada pode ocasionar eventos tromboembólicos e hemorrágicos, representando um desafio para a medicina. A varfarina, anticoagulante oral de amplo uso, está associada a reações adversas graves, frequentes nos pacientes em tratamento com múltiplos fármacos. Objetivo: Este estudo pretende avaliar as potenciais interações medicamentosas com a varfarina, descrever e quantificar as intervenções farmacêuticas para minimizá-las, verificar o grau de aceitação da equipe médica em relação às intervenções e a repercussão no resultado do RNI. Método: Estudo de coorte, realizado entre os meses de agosto de 2009 a janeiro de 2010, envolvendo pacientes internados que iniciaram o tratamento com varfarina em duas unidades de clínica médica em um hospital universitário localizado no sul do Brasil. As potenciais interações medicamentosas com a varfarina (graves e moderadas) foram identificadas no sistema Drug-Reax, Micromedex Healthcare. Outras informações foram obtidas diretamente no prontuário. As intervenções com a equipe médica ocorreram por meio de registro em prontuário ou por informação verbal. O valor do RNI (Relação Normatizada Internacional) foi constantemente monitorado e serviu como medida do resultado da intervenção. Resultados: Foram acompanhados 202 pacientes. O total de medicamentos prescritos foi de 2071, com média de 10 (DP=3,6) por paciente. Todos pacientes apresentaram pelo menos uma interação medicamentosa potencial grave ou moderada com a varfarina, sendo a média de 3,6 (DP=1,6) por paciente. Pacientes com mais de 4 interações medicamentosas potenciais apresentaram maior risco para eventos hemorrágicos (RNI > 5 - RR = 2,57; IC95% 1,37–4,80). Foram identificadas 737 potenciais interações; 675 (91,5%) com possibilidade de potencializar o efeito anticoagulante e 29 (3,9%) de reduzir este efeito. Os medicamentos mais envolvidos em interações de potencialização foram enoxaparina (32,2%), sinvastatina (27,6%), omeprazol (22,5%) e tramadol (21,5%). Das intervenções realizadas com a equipe médica, 116 (57,4%) se deram através de registros em prontuário e 86 (42,6%) de forma verbal. Para 32 pacientes (15,8%) as intervenções não foram aceitas e estes apresentaram maior risco (RR = 2,17; IC95% 1,10 –4,27) para exame alterado (RNI > 5). Análise multivariada mostrou que idade, tempo de internação, apresentar 4 ou mais interações potenciais graves ou moderadas e não aceitar a intervenção farmacêutica contribuem significativamente para o paciente apresentar resultado de RNI > 5, o que implica em risco para eventos hemorrágicos. Conclusão: Interações medicamentosas graves e moderadas envolvendo a varfarina são muito comuns nos pacientes internados e estão associadas à maior risco do paciente apresentar RNI fora da faixa terapêutica desejada. A participação do farmacêutico no manejo das interações através de informações e orientações aos prescritores mostrou ter boa aceitação em nosso meio e parece contribuir para a segurança do paciente. / Introduction: Inadequate anticoagulation may cause bleeding and thromboembolic events, representing a challenge for medicine. Warfarin, an oral anticoagulant in wide use, has severe adverse reactions, common in patients taking multiple drugs. Objectives: This study aims to evaluate potential drug interactions with warfarin; to describe and quantify pharmaceutical interventions in order to minimize them; to assess the degree of acceptability by the medical team in relation to interventions as well as the impact on the outcome of the INR. Method: A Cohort study, done between August 2009 and January 2010 involving hospitalized patients who started warfarin therapy in two internal medicine units in a university hospital located in southern Brazil. Potential pDDIs with warfarin with warfarin (major and moderate) were identified in the online system Drug-Reax, Micromedex Healthcare. Additional information was obtained directly from medical records. Interventions with medical team were through medical record notes or verbal information. The value of the INR (international normalized ratio) was continuously monitored and served as a measure of the outcome of the intervention. Results: Two hundred and two inpatients were followed. The total number of prescribed drugs was 2071, with mean of 10 (SD = 3.6) per patient. All inpatients had at least one potential moderate or severe pDDIs with warfarin, the mean was 3.6 (SD = 1.6) per patient. Patients with more than four potential drug interactions showed a higher risk for hemorrhagic problems (INR> 5 - RR = 3.00, 95% CI 1.59-5.70). For 737 pDDIs identified, 675 (91.5%) may result in increased anticoagulation activity and 29 (3.9%) may reduce this effect. The drugs most commonly involved in these pDDIs were enoxaparin (32.2%), simvastatin (27.6%), omeprazole (22.5%) and tramadol (21.5%). The medical team’s intervention were 116 (57.4%) through medical records and 86 (42.6%) were orally. For 32 patients (15.8%), interventions were not accepted and they had higher risk (RR = 2.17; 95% CI 1.10 – 4.27) for amended exam (INR > 5). Multivariate analysis showed that age, length of hospital stay, having four or more major or moderate potential interactions and unwillingness to accept pharmaceutical intervention contribute significantly to the patient current values of INR> 5, which implies a risk of bleeding. Conclusion: Major and moderate drug interactions involving warfarin are very common in hospitalized patients and are associated with patient’s high risk of having an INR outside the target range. The collaboration of pharmacists in the management of interactions with information and guidance to physicians showed a good acceptance and seems to contribute to patient safety.

A anticoagulação inadequada pode ocasionar eventos tromboembólicos e hemorrágicos, representando um desafio para a medicina. A varfarina, anticoagulante oral de amplo uso, está associada a reações adversas graves, frequentes nos pacientes em tratamento com múltiplos fármacos. Objetivo: Este estudo pretende avaliar as potenciais interações medicamentosas com a varfarina, descrever e quantificar as intervenções farmacêuticas para minimizá-las, verificar o grau de aceitação da equipe médica em relação às intervenções e a repercussão no resultado do RNI. Método: Estudo de coorte, realizado entre os meses de agosto de 2009 a janeiro de 2010, envolvendo pacientes internados que iniciaram o tratamento com varfarina em duas unidades de clínica médica em um hospital universitário localizado no sul do Brasil. As potenciais interações medicamentosas com a varfarina (graves e moderadas) foram identificadas no sistema Drug-Reax, Micromedex Healthcare. Outras informações foram obtidas diretamente no prontuário. As intervenções com a equipe médica ocorreram por meio de registro em prontuário ou por informação verbal. O valor do RNI (Relação Normatizada Internacional) foi constantemente monitorado e serviu como medida do resultado da intervenção. Resultados: Foram acompanhados 202 pacientes. O total de medicamentos prescritos foi de 2071, com média de 10 (DP=3,6) por paciente. Todos pacientes apresentaram pelo menos uma interação medicamentosa potencial grave ou moderada com a varfarina, sendo a média de 3,6 (DP=1,6) por paciente. Pacientes com mais de 4 interações medicamentosas potenciais apresentaram maior risco para eventos hemorrágicos (RNI > 5 - RR = 2,57; IC95% 1,37–4,80). Foram identificadas 737 potenciais interações; 675 (91,5%) com possibilidade de potencializar o efeito anticoagulante e 29 (3,9%) de reduzir este efeito. Os medicamentos mais envolvidos em interações de potencialização foram enoxaparina (32,2%), sinvastatina (27,6%), omeprazol (22,5%) e tramadol (21,5%). Das intervenções realizadas com a equipe médica, 116 (57,4%) se deram através de registros em prontuário e 86 (42,6%) de forma verbal. Para 32 pacientes (15,8%) as intervenções não foram aceitas e estes apresentaram maior risco (RR = 2,17; IC95% 1,10 –4,27) para exame alterado (RNI > 5). Análise multivariada mostrou que idade, tempo de internação, apresentar 4 ou mais interações potenciais graves ou moderadas e não aceitar a intervenção farmacêutica contribuem significativamente para o paciente apresentar resultado de RNI > 5, o que implica em risco para eventos hemorrágicos. Conclusão: Interações medicamentosas graves e moderadas envolvendo a varfarina são muito comuns nos pacientes internados e estão associadas à maior risco do paciente apresentar RNI fora da faixa terapêutica desejada. A participação do farmacêutico no manejo das interações através de informações e orientações aos prescritores mostrou ter boa aceitação em nosso meio e parece contribuir para a segurança do paciente. / Introduction: Inadequate anticoagulation may cause bleeding and thromboembolic events, representing a challenge for medicine. Warfarin, an oral anticoagulant in wide use, has severe adverse reactions, common in patients taking multiple drugs. Objectives: This study aims to evaluate potential drug interactions with warfarin; to describe and quantify pharmaceutical interventions in order to minimize them; to assess the degree of acceptability by the medical team in relation to interventions as well as the impact on the outcome of the INR. Method: A Cohort study, done between August 2009 and January 2010 involving hospitalized patients who started warfarin therapy in two internal medicine units in a university hospital located in southern Brazil. Potential pDDIs with warfarin with warfarin (major and moderate) were identified in the online system Drug-Reax, Micromedex Healthcare. Additional information was obtained directly from medical records. Interventions with medical team were through medical record notes or verbal information. The value of the INR (international normalized ratio) was continuously monitored and served as a measure of the outcome of the intervention. Results: Two hundred and two inpatients were followed. The total number of prescribed drugs was 2071, with mean of 10 (SD = 3.6) per patient. All inpatients had at least one potential moderate or severe pDDIs with warfarin, the mean was 3.6 (SD = 1.6) per patient. Patients with more than four potential drug interactions showed a higher risk for hemorrhagic problems (INR> 5 - RR = 3.00, 95% CI 1.59-5.70). For 737 pDDIs identified, 675 (91.5%) may result in increased anticoagulation activity and 29 (3.9%) may reduce this effect. The drugs most commonly involved in these pDDIs were enoxaparin (32.2%), simvastatin (27.6%), omeprazole (22.5%) and tramadol (21.5%). The medical team’s intervention were 116 (57.4%) through medical records and 86 (42.6%) were orally. For 32 patients (15.8%), interventions were not accepted and they had higher risk (RR = 2.17; 95% CI 1.10 – 4.27) for amended exam (INR > 5). Multivariate analysis showed that age, length of hospital stay, having four or more major or moderate potential interactions and unwillingness to accept pharmaceutical intervention contribute significantly to the patient current values of INR> 5, which implies a risk of bleeding. Conclusion: Major and moderate drug interactions involving warfarin are very common in hospitalized patients and are associated with patient’s high risk of having an INR outside the target range. The collaboration of pharmacists in the management of interactions with information and guidance to physicians showed a good acceptance and seems to contribute to patient safety.