Yes / Warfarin and direct oral anticoagulants (DOACs) have been shown to reduce the risk of stroke in patients with atrial fibrillation, yet many patients are still not being anticoagulated. This article discusses the barriers to the initiation of oral anticoagulants, in particular DOACs, and how these can be overcome.

Adverse drug reactions (ADRs) constitute a significant health problem with consequences for the patient as well as for society. Suspected ADRs have been reported to occur in about 2-14% of hospitalised patients. In about 5% of deceased hospitalised patients suspected ADRs may have caused or contributed to the fatal outcome. When a pharmaceutical drug is approved for marketing, the drug has been tested only on a limited number of patients (often <6000) for a limited time period in a controlled environment. Hence mostly common ADRs are detected in these trials. Moreover, certain patient groups, for example patients with co-morbidities, elderly patients, children and pregnant women are often not included in these studies. Thus, it is important to closely monitor the use of drugs after marketing to observe new effects and detect new ADRs. The aim of this thesis is to describe the pattern of pharmaceutical substance use related to morbidity and mortality and to investigate two serious ADRs. We have studied the incidence of fatal ADRs, fatal intoxications, cerebral haemorrhage related to warfarin treatment and venous thromboembolism (VTE) related to treatment with antipsychotic drugs. Observational studies form the basis for this thesis. Data from the Swedish Cause of Death Register, medical case records, the Swedish database on ADRs, the forensic pathology and forensic toxicology databases, and Swedish and Danish hospital discharge registers, Danish prescription registers, and civil registry systems were used. In Paper I we found that 3% of all fatalities in a Swedish population were related to a suspected ADR. Of the deceased hospitalised patients, 6% were related to a suspected ADR. Haemorrhage was the most commonly observed fatal suspected ADR, accounting for almost two-thirds of the events and anticoagulantia was the most common drug group associated with fatal suspected ADRs (almost 50%). A suspected intoxication could have contributed to the fatal outcome in 0.6% of the deceased. Among the fatal intoxications in Swedish medico-legal autopsies studied in Paper II, on average four substances were detected per case. The five most commonly detected substances in individuals with a fatal intoxication were ethanol, propoxyphene, paracetamol, diazepam and flunitrazepam. Among patients diagnosed with cerebral haemorrhage, 10% (59 cases) were treated with warfarin at onset of symptoms (Paper III). Of these, 7 cases (12%) were considered to have been possibly avoidable since the patients were treated with concomitant drugs that have the potential to enhance warfarin effects. The results from Paper IV and Paper V in combination with the published literature suggest that patients treated with antipsychotic drugs have an increased risk for VTE. Compared with non-users, an adjusted odds ratio for VTE of 2.0 was found for users of any antipsychotic drugs in a Danish population. In a medico-legal autopsy series, an adjusted odds ratio for fatal pulmonary embolism of 2.4 and 6.9 was found for users of first-generation low-potency antipsychotics and second-generation antipsychotics, respectively. In summary, drug-related morbidity and mortality is a significant problem and suspected ADRs contribute to a substantial number of deaths. Fatal intoxications are relatively common and it is important to observe changes in patterns of substances associated with fatal intoxications to be able to discover new trends and monitor effects of preventive work. A significant proportion of warfarin-related cerebral haemorrhage was caused by drug-drug interactions and was considered possible to avoid. Users of antipsychotic drugs may increase the risk of VTE. / Idag finns det säkra och effektiva behandlingar mot många sjukdomar. Läkemedel är den vanligaste behandlingsformen i sjukvården och under 2006 hämtade sex miljoner svenskar (68%) ut ett eller fler recept på ett apotek i Sverige. Även om läkemedelsbehandling har många positiva effekter kan även oönskade och skadliga effekter vid läkemedelsbehandling uppkomma, dvs. läkemedelsbiverkningar. Innan ett läkemedel kommer ut för försäljning har man studerat effekter och biverkningar på ett begränsat antal individer (ofta <6000) under en begränsad tidsperiod där patienterna övervakas noga. Dessutom är det i regel enbart patienter med få andra sjukdomar och läkemedel som ingår i dessa studier. Därför är oftast enbart de vanligaste biverkningarna kända när ett läkemedel börjar säljas till allmänheten. När ett läkemedel blir tillgängligt för ett stort antal patienter är det därför viktigt att man med olika metoder fortsätter att följa läkemedlets effekter och biverkningar. Tidigare har man visat att ungefär 2-14% av inläggningar på sjukhus beror på läkemedelsbiverkningar. Dessutom kan biverkningar ha bidragit eller orsakat dödsfallet i ungefär 5% av de som avlider på sjukhus. Biverkningar orsakar mycket lidande för patienten och kostar samhället både tid och pengar. Om det skulle vara möjligt att förhindra några av dessa sjukhusinläggningar eller dödsfall skulle man vinna mycket. Det är svårt att uppskatta hur många biverkningar som kan förhindras. Genom att studera faktorer som kan öka risken för en oönskad effekt kan man bättre anpassa behandlingen till den enskilde patienten och därmed förhindra biverkningar. Syftet med den här avhandlingen är att beskriva mönster av läkemedelsrelaterade sjukdomar och dödsfall, och att undersöka risken för två allvarliga läkemedelsbiverkningar. Förekomsten av misstänkta läkemedelsbiverkningar, vilka faktorer som kan öka risken för att få en läkemedelsbiverkan, samt vilka läkemedel och biverkningar som förekommer har studerats. Detta gjordes utifrån uppgifter hämtade från dödsorsaksregistret, svenska biverkningsregistret, journaler, rättsmedicinska register, slutenvårdsregister och receptregister. Genom att utnyttja sådan information har vi i närmare detalj studerat förekomsten av dödsfall där ett eller flera läkemedel kan ha haft betydelse för dödsfallet, förgiftningsdödsfall, blödningar i samband med blodförtunnande medicinering och blodproppar i samband med antipsykotisk medicinering. I de arbeten som ingår i avhandlingen har vi funnit att en läkemedelsbiverkan misstänks ha bidragit eller orsakat dödsfallet i ungefär 3% av de som avlidit i en svensk population (Arbete I). Blödningar står för nästan två tredjedelar av dessa biverkningar och blodförtunnande medel misstänks vara inblandade i nästan hälften av de misstänkta läkemedelsbiverkningarna. I den här svenska populationen avled 0,6% till följd av misstänkt läkemedelsförgiftning. Bland rättsmedicinskt undersökta förgiftningsdödsfall påvisades i genomsnitt fyra substanser per fall (Arbete II). De fem vanligaste påvisade substanserna i studien var alkohol, dextropropoxifen, paracetamol, diazepam och flunitrazepam. Bland patienter som får hjärnblödning behandlades 10% vid blödningstillfället med ett blodförtunnande medel, warfarin (Arbete III). I 7 fall (12%) skulle hjärnblödningen möjligen kunna ha förhindrats då patienterna samtidigt behandlades med andra läkemedel som kan ha ökat blödningsrisken. Den sammantagna bilden av den litteratur som finns publicerad och resultatet av Arbete IV och Arbete V, tyder på att patienter som behandlas med antipsykotiska preparat har en ökad risk för att få blodpropp. Flera faktorer har föreslagits som kan förklara den ökade risken för blodpropp bland patienter som behandlas med antipsykotika som har med sjukdomen att göra och/eller behandlingen med antipsykotiska läkemedel. Sammanfattningsvis visar detta avhandlingsprojekt att läkemedelsbiverkningar är ett väsentligt sjukvårdsproblem som bidrar till ett betydande antal dödsfall. Förgiftningsdödsfall med läkemedel är också relativt vanliga och det är viktigt att bevaka effekter av preventiva åtgärder och se om de substanser som används ändras över tid. En del läkemedelsrelaterade biverkningar skulle kunna förhindras då t.ex. en betydande andel av warfarinrelaterade hjärnblödningar beror på läkemedelsinteraktioner. Förekomsten av venösa blodproppar verkar vara förhöjd bland patienter som behandlas med antipsykotiska läkemedel, men fler studier behövs för att avgöra detta och vad det i så fall beror på.

Un apport élevé de vitamine K a été associé à une meilleure stabilité du traitement à la warfarine. Toutefois, l’effet du gène VKORC1, codant pour une enzyme impliquée dans le métabolisme de la vitamine K et inhibée par la warfarine, sur cette association a été très peu étudié. De plus, il a été suggéré que les patients anticoagulés sont fréquemment conseillés de restreindre leur consommation d’aliments riches en vitamine K dans le contexte clinique. Néanmoins, l’effet de cette recommandation sur l’apport de vitamine K n’est pas établi. Afin d’examiner ces questions, 317 Québécois anticoagulés à la warfarine provenant de 17 sites hospitaliers ont été sondés sur les recommandations alimentaires reçues en début de traitement. L’apport alimentaire habituel de vitamine K a été évalué rétrospectivement sur une période de 12 mois. La stabilité du traitement a été mesurée par le pourcentage de temps passé dans l’intervalle thérapeutique (n=246) du 3e au 12e mois suivant l’initiation du traitement. La majorité des patients (68%) ont rapporté avoir été conseillés de restreindre leur consommation d’aliments riches en vitamine K. L’adhérence à cette recommandation était associée à de plus faibles apports alimentaires de vitamine K. De plus, l’apport alimentaire de vitamine K était positivement associé à la stabilité du traitement, et cette relation n’était pas modulée par le génotype de VKORC1. Ces données ont permis d’illustrer des lacunes dans l’éducation nutritionnelle prodiguée aux patients anticoagulés à la warfarine, et ont contribué à la recherche portant sur l’interaction entre l’apport de vitamine K et la warfarine. / Recent studies suggest that higher vitamin K intake is associated with better warfarin therapy stability. However, whether the VKORC1 gene, encoding an enzyme involved in vitamin K metabolism and inhibited by warfarin, modulates this association is not well studied. Moreover, it has been suggested that warfarin-treated patients are often instructed to limit their consumption of vitamin K-rich foods in the clinical setting. Yet, the impact of this advice on usual dietary vitamin K intakes is unknown. To gain insight in these issues, 317 warfarin-treated patients from 17 hospital sites in the province of Quebec were questioned on the dietary recommendations they had received at warfarin initiation. Usual dietary vitamin K intake was assessed retrospectively over a 12-month period. Stability of warfarin therapy was measured by the percentage of time in the therapeutic range (n=246) from the 3rd to 12th month following warfarin initiation. Most patients (68%) reported being advised to limit their consumption of vitamin K-rich foods, particularly green vegetables. Adherence to this recommendation was associated with lower vitamin K intakes. Moreover, usual dietary vitamin K intake was positively associated with warfarin therapy stability. This association was not modulated by VKORC1 genotype. These data highlighted the need for better nutritional education in warfarin users, and contributed to the research on the interaction between dietary vitamin K intake and warfarin.

Introdução. A varfarina tem sido considerada a principal terapêutica anticoagulante oral há aproximadamente 50 anos, estando entre os dez medicamentos mais envolvidos com reações adversas a medicamentos (RAM), apresenta estreita janela terapêutica e complexo regime posológico, exibe enorme variabilidade doseresposta e elevado risco de interações medicamentosas (IM). Objetivo. Identificar e avaliar as IM e RAM relacionadas com a administração da varfarina. Casuística e Métodos. Trata-se de um estudo transversal. Os dados foram coletados retrospectivamente através do banco de dados informatizado do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo pertencente ao Sistema Único de Saúde. As prescrições de janeiro/2004 a dezembro/2010 dos pacientes que utilizaram varfarina foram analisadas, sendo os pacientes divididos em dois grupos: estudo (uso de vitamina K até 168 horas após prescrição de varfarina) e controle. Posteriormente, as prescrições medicamentosas que não continham varfarina foram excluídas da análise. As informações coletadas incluíram idade, gênero, raça, unidade de atendimento, diagnóstico clínico, doses e medicamentos, e exames laboratoriais. As IM com varfarina foram classificadas em risco A, B, C, D e X de acordo a base de dados da Lexi-Interact(TM) Online. Foi realizada análise descritiva e analítica (p<0,05). Resultados e Discussão. Foram identificados 3048 pacientes, os quais receberam 154161 prescrições medicamentosas (42120 continham varfarina). A idade média foi de 55,8 (±19,3) anos, 53,2% do gênero feminino, prevalência de idosos (48,1%) e do diagnóstico outras doenças cerebrovasculares específicas (4,3%). Os valores médios da international normalized ratio (INR) (2,4±1,7) e dose de varfarina (5,1±1,8mg) encontraram-se dentro dos preconizados pelos protocolos terapêuticos. Foi observado que 66,4% dos pacientes realizaram uso de polifarmácia, o que pode elevar o risco de IM. Além disso, 63,2% dos pacientes apresentaram prescrição(ões) de medicamentos classificados como risco D e/ou X, com média de 1,4 (±0,4) medicamento/prescrição, destacando-se o ácido acetilsalicílico e amiodarona. Quando comparado grupo de estudo (n=429) versus controle (n=2619), houve diferença estatisticamente significativa na idade média (anos) (59,0±18,8 vs. 55,5±19,3; p<0,000), número médio de medicamentos/prescrição (7,1±2,8 vs. 6,2±2,8; p<0,000), número médio de medicamentos de Risco D e X de IM por prescrição (1,4±1,3 vs. 1,0±1,0; p<0,000), albumina sérica (g/dL) (3,4±0,6 vs. 3,7±0,6; p<0,000), aspartato aminotransferase (U/L) (60,7± 200,6 vs. 41,5±84,5; p<0,005) e INR (4,9±3,4 vs. 2,1±0,7; p<0,000), fatores estes que podem ter contribuído para ocorrência de RAM no grupo de estudo. Conclusão. Observou-se elevada ocorrência de possíveis IM e RAM nos usuários de varfarina, as quais podem comprometer a efetividade e segurança do tratamento farmacológico. Como possíveis fatores de risco para ocorrência de RAM, destacam-se elevados valores de idade, número de medicamentos/prescrição, prescrição de medicamentos classificados como risco D e/ou X, de INR e de aspartato aminotransferase, e valores diminuídos de albumina sérica. / Introduction. Warfarin has been considered the main oral anticoagulant therapy about 50 years ago and is among the ten drugs most commonly involved in adverse drug reactions (ADR), has a narrow therapeutic index and complex dosage regimen, exhibits enormous variability dose-response and high risk drug-drug interactions (DDI). Objective. To Identify and evaluate DDI and ADR related to the administration of warfarin. Casuistry and Methods. This was a cross sectional study. Data were collected retrospectively through the computerized database of the Faculty of Medicine of Ribeirao Preto Hospital, University of Sao Paulo linked to the Unified Health System. The prescriptions of the January/2004 to December/2010 of patients using warfarin were analyzed, and the patients were divided into two groups: study (utilization of vitamin K until 168 hours after prescribing warfarin) and control. Thereafter, the drug prescriptions that did not contain warfarin were excluded from analysis. Information collected included age, gender, race, patient service center, clinical diagnosis, dosages and drugs, and laboratory exams. The warfarin DDI were classified at risk A, B, C, D and X according to the database Lexi-Interact (TM) Online. Descriptive and analytical analysis were performed (p<0.05). Results and Discussion. We identified 3048 patients who received 154,161 drug prescriptions (42,120 contained warfarin). The mean age was 55.8 (±19.3) years, 53.2% female, prevalence of elderly (48.1%) and other cerebrovascular diseases specific diagnosis (4.3%). The average values of international normalized ratio (INR) (2.4±1.7) and warfarin dose (5.1±1.8mg) were within those recommended by therapeutic protocols. It was observed that 66.4% of patients received polypharmacy, which can raise the risk of DDI. In addition, 63.2% of patients had prescription(s) of drugs classified as D or X risk, with an average of 1.4 (±0.4) drugs per prescription, especially aspirin and amiodarone. Compared study group (n=429) versus control (n =2619), there was a statistically significant difference in mean age (years) (59.0±18.8 vs. 55.5±19.3; p<0.000), average number of medications/prescriptions (7.1±2.8 vs. 6.2±2.8; p<0.000), mean number of drugs with risk D and X DDI/prescription (1.4±1.3 vs. 1.0±1.0, p<0.000), serum albumin (g/dL) (3.4±0.6 vs. 3.7±0.6; p<0.000), aspartate aminotransferases (U/L) (60.7±200.6 vs. 41.5±84.5; p<0.005) and INR (4.9±3.4 vs. 2.1±0.7; p<0.000), factors that may have contributed to the occurrence of ADR in the study group. Conclusion. There was a high occurrence of possible DDI and ADR in patients treated with warfarin, which may compromise the effectiveness and safety of pharmacological treatment. Noteworthy is the high values of age, number of medications/prescriptions, prescription drugs classified as risk D or X, INR and aspartate aminotransferases, and lower values of serum albumin as potential risk factors for the occurrence of ADR.

Varfarina é o anticoagulante oral prescrito com maior frequência, no entanto há difi-culdades em seu manejo na prática clínica. Embora tenha eficácia bem estabelecida é considerado um medicamento potencialmente perigoso, que está associado a erros de medicação fatais na atenção primária à saúde. Para garantir a segurança do paciente, seu uso requer o monitoramento dos níveis de anticoagulação, sendo importante a ade-são ao tratamento e a informação dos pacientes quanto aos cuidados durante o trata-mento. O objetivo do presente estudo foi verificar o nível de informações dos pacien-tes quanto à prescrição, o nível de informações prestadas pela equipe de saúde aos pa-cientes, a adesão ao tratamento e os níveis de controle da anticoagulação através do valor do Coeficiente Internacional Normatizado (INR). Foi realizado estudo transver-sal, a partir de uma coorte prospectiva, com 60 pacientes atendidos na atenção primá-ria à saúde no município de Ijuí, utilizando-se questionário para verificar o nível de informação prestada aos pacientes pela equipe de sáude, a Escala de Adesão Terapêu-tica de Morisky de Oito Itens para verificar a adesão, e o exame do tempo de protrom-bina para verificar o valor INR. De acordo com os critérios adotados, verificou-se um nível insuficiente de informações prestada pela equipe de saúde, baixa adesão ao tra-tamento, com a maioria dos pacientes fora do intervalo terapêutico adequado. Verifica-se a necessidade de melhoria da qualidade das informações prestadas aos usuários, incentivo da adesão ao tratamento e melhor monitoramento da anticoagulação visando à segurança do paciente. / Warfarin is the oral anticoagulant most frequently prescribed, although is difficult handling warfarin in clinical practice. It’s has a well-established efficacy, but is con-sidered a potentially dangerous drug, and in primary health care is associated with fatal medication errors. To ensure patient safety, its use requires requires anticoagulation levels monitoring ,, so medication adherence and care information’s about anticoagula-tion therapy are important. The aim of this study was to verify the information level about the prescription, information level provided by the health care team, medication adherence and anticoagulation control levels by the International Normalized Ratio (INR) value. A cross-sectional study, from a prospective cohort, was realized with 60 patients seen in primary health care in Ijuí city, a questionnaire was use to check the information level to the patients by the health team, Eight Item Morisky Medication Adherence Scale was use to verify adherence, and prothrombin time exam was use to check the INR value. According to the criteria adopted, was observed insufficient in-formation level provided by health care team, poor adherence to treatment and most patients was out of the therapeutic range. It’s necessary improve the quality of infor-mation provided to the patients, promote medication adherence and improve the anti-coagulation monitoring for patient safety in the treatment.

Background: Malignancy is a significant risk factor for venous thromboembolism (VTE), conferring a 4- to 7-fold increased risk in patients with cancer. Because of its effect on certain tumors, low-molecular-weight heparin (LMWH) has been evaluated as a treatment option for cancer and as an alternative to traditional warfarin therapy in patients with active cancer. LMWH is associated with a reduced recurrence of VTE, fewer adverse bleeding events, and, in some instances, decreased mortality. The American College of Chest Physicians/American Society of Clinical Oncology has recommended LMWH for at least the initial 3 to 6 months when treating VTE in patients with cancer, based on the positive outcomes associated with LMWH. Objective: The purpose of this study was to evaluate physician prescribing patterns for LMWH or warfarin in patients with acute VTE and active cancer. Methods: We conducted a retrospective chart review of hospitalized patients at a community teaching hospital with an affiliated regional cancer center located in a rural area of the United States. Patients included in the analysis had an International Classification of Diseases, Ninth Revision code indicative of any cancer type and a concomitant code for any VTE. The primary outcome was the drug prescribed at discharge for the treatment of VTE. Secondary outcomes included specialty of the prescribing physician, adverse bleeding events, and the need for transfusion. VTE treatment regimen was evaluated using the binomial test, and logistic regression analysis was used to determine correlation of the prescriber’s specialty with the patient’s prescribed regimen. Results: Of 129 patients included in the analysis, 107 (82.9%) were prescribed warfarin compared with 9 (7%) who were prescribed LMWH. Hematologists and oncologists were more likely to prescribe LMWH than general practitioners (odds ratio, 7.8; 95% hazard ratio, 1.5-42). Seven patients had a documented adverse bleeding event and 2 patients required a transfusion. Four of the 7 adverse bleeding events and 1 of the 2 transfusions occurred in the group receiving vitamin K antagonist therapy. Conclusion: Physicians in our system were significantly more likely to prescribe warfarin for acute treatment of VTE in patients with active cancer—despite consistent evidence and multiple evidence­-based guidelines recommending treatment with LMWH in this patient population. This was lower than other observations in Canadian populations but may more accurately represent nonteaching centers in the United States, particularly those in rural areas. Specialists in oncology were significantly more likely to prescribe LMWH than generalists.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Feb. 19, 2010). Includes bibliographical references.

Made available in DSpace on 2015-07-22T20:50:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-11-25. Added 1 bitstream(s) on 2015-08-11T03:25:34Z : No. of bitstreams: 1 Publico-020a.pdf: 165301 bytes, checksum: 478022db64b034bbea30c204bbaf2cb9 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:34Z : No. of bitstreams: 2 Publico-020a.pdf: 165301 bytes, checksum: 478022db64b034bbea30c204bbaf2cb9 (MD5) Publico-020b.pdf: 118674 bytes, checksum: 3222abfa356d637cdb4ac8248c91cf7a (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:35Z : No. of bitstreams: 3 Publico-020a.pdf: 165301 bytes, checksum: 478022db64b034bbea30c204bbaf2cb9 (MD5) Publico-020b.pdf: 118674 bytes, checksum: 3222abfa356d637cdb4ac8248c91cf7a (MD5) Publico-020c.pdf: 2073396 bytes, checksum: 04ba8e01c6f7b4dd2421e5babffdd4b9 (MD5) / Um número desconhecido de pacientes com câncer experimenta reações e interações de drogas graves, podendo resultar em hospitalização e até em morte. Particularmente, pacientes portadores de neoplasia maligna comumente recebem um grande número de medicamentos, além de receberem drogas com alto risco de efeitos adversos. Desta forma, dois estudos foram realizados como base para esta tese: uma revisão sistemática e em estudo retrospectivo. A revisão sistemática da literatura avaliou os estudos publicados sobre a epidemiologia de interações medicamentosas em pacientes com câncer. A busca identificou 8 estudos: 7 artigos publicados no PubMed e um resumo publicado nos proceedings do congresso da sociedade americana de oncologia (ASCO). A maioria dos estudos era retrospectiva e avaliou potenciais interações medicamentosas, com apenas dois estudos publicados sobre reais interações medicamentosas. Aparentemente, um terço dos pacientes oncológico ambulatoriais recebe combinações de drogas com risco de interação. Os principais fatores de risco para interações medicamentosas são: idade avançada, número crescente de medicações, presença de lesões cerebrais (primárias ou secundárias) e pacientes que recebem drogas consideradas de risco como anticonvulsivantes, varfarina e anti-inflamatórios hormonais e não-hormonais. O segundo estudo desta tese avaliou a prevalência de potenciais interações medicamentosas entre pacientes com câncer terminal. Desta forma, nós revisamos retrospectivamente os prontuários de todos os pacientes com câncer que foram atendidos no ambulatório de Cuidados Paliativos, do Hospital Princess Margaret, Toronto, Canadá, num período de 8 meses. As listas de medicações foram rastreadas para interações pelo programa eletrônico Drug Interaction Facts, que classifica as interações por nível de gravidade (maior, moderada e menor) e evidência científica (1 a 5, onde 1 = maior nível de evidência). Dentre os 372 pacientes avaliados, 250 interações medicamentosas potenciais foram identificadas em 115 pacientes (31%, 95% Intervalo de Confiança 26 - 36%), predominantemente envolvendo varfarina e fenitoína. A maioria das potenciais interações foi classificada como de gravidade moderada (59%) e 41,5% possuíam níveis de evidência 1-3. Na análise multivariada, idade crescente (p<0,001), pelo menos uma comorbidade (p=0,001), tipo de câncer (tumores cerebrais, p<0,001) e número crescente de medicamentos utilizados (p<0,001) foram associados a risco de interações medicamentosas. Portanto, concluiu-se que potenciais interações medicamentosas são comuns entre pacientes oncológicos que estejam recebendo cuidados de suporte exclusivos, sendo que a maioria envolve varfarina e/ou anticonvulsivantes. Fatores de risco incluem idade avançada, pacientes com múltiplas comorbidades, tumores cerebrais e aqueles que utilizam muitas medicações. / Background: Drug-drug interactions (DDIs) comprise an important problem in medical oncology practice. We systematically reviewed the frequency of DDIs in oncology. Methods: We searched PubMed for eligible articles and online databases abstracts of major oncology meetings. Results: Eight studies reported on the frequency of DDIs: six evaluated the frequency of potential DDIs while 2 studies reported on real DDIs, i.e. interactions that had clinical consequences. Studies of potential DDIs found that approximately one third of patients are exposed to dangerous drug doublets, with the most common ones involving warfarin and anticonvulsants. One study of real DDIs found that 2% of hospitalized cancer patients had a DDI as the cause of admission. Conclusion: Drug interactions comprise an important issue in oncology, with approximately one third of ambulatory cancer patients being at risk of DDIs. Data are limited on the clinical consequences of drug interactions among cancer patients. / TEDE / BV UNIFESP: Teses e dissertações

Varfarina é o anticoagulante oral prescrito com maior frequência, no entanto há difi-culdades em seu manejo na prática clínica. Embora tenha eficácia bem estabelecida é considerado um medicamento potencialmente perigoso, que está associado a erros de medicação fatais na atenção primária à saúde. Para garantir a segurança do paciente, seu uso requer o monitoramento dos níveis de anticoagulação, sendo importante a ade-são ao tratamento e a informação dos pacientes quanto aos cuidados durante o trata-mento. O objetivo do presente estudo foi verificar o nível de informações dos pacien-tes quanto à prescrição, o nível de informações prestadas pela equipe de saúde aos pa-cientes, a adesão ao tratamento e os níveis de controle da anticoagulação através do valor do Coeficiente Internacional Normatizado (INR). Foi realizado estudo transver-sal, a partir de uma coorte prospectiva, com 60 pacientes atendidos na atenção primá-ria à saúde no município de Ijuí, utilizando-se questionário para verificar o nível de informação prestada aos pacientes pela equipe de sáude, a Escala de Adesão Terapêu-tica de Morisky de Oito Itens para verificar a adesão, e o exame do tempo de protrom-bina para verificar o valor INR. De acordo com os critérios adotados, verificou-se um nível insuficiente de informações prestada pela equipe de saúde, baixa adesão ao tra-tamento, com a maioria dos pacientes fora do intervalo terapêutico adequado. Verifica-se a necessidade de melhoria da qualidade das informações prestadas aos usuários, incentivo da adesão ao tratamento e melhor monitoramento da anticoagulação visando à segurança do paciente. / Warfarin is the oral anticoagulant most frequently prescribed, although is difficult handling warfarin in clinical practice. It’s has a well-established efficacy, but is con-sidered a potentially dangerous drug, and in primary health care is associated with fatal medication errors. To ensure patient safety, its use requires requires anticoagulation levels monitoring ,, so medication adherence and care information’s about anticoagula-tion therapy are important. The aim of this study was to verify the information level about the prescription, information level provided by the health care team, medication adherence and anticoagulation control levels by the International Normalized Ratio (INR) value. A cross-sectional study, from a prospective cohort, was realized with 60 patients seen in primary health care in Ijuí city, a questionnaire was use to check the information level to the patients by the health team, Eight Item Morisky Medication Adherence Scale was use to verify adherence, and prothrombin time exam was use to check the INR value. According to the criteria adopted, was observed insufficient in-formation level provided by health care team, poor adherence to treatment and most patients was out of the therapeutic range. It’s necessary improve the quality of infor-mation provided to the patients, promote medication adherence and improve the anti-coagulation monitoring for patient safety in the treatment.

Varfarina é o anticoagulante oral prescrito com maior frequência, no entanto há difi-culdades em seu manejo na prática clínica. Embora tenha eficácia bem estabelecida é considerado um medicamento potencialmente perigoso, que está associado a erros de medicação fatais na atenção primária à saúde. Para garantir a segurança do paciente, seu uso requer o monitoramento dos níveis de anticoagulação, sendo importante a ade-são ao tratamento e a informação dos pacientes quanto aos cuidados durante o trata-mento. O objetivo do presente estudo foi verificar o nível de informações dos pacien-tes quanto à prescrição, o nível de informações prestadas pela equipe de saúde aos pa-cientes, a adesão ao tratamento e os níveis de controle da anticoagulação através do valor do Coeficiente Internacional Normatizado (INR). Foi realizado estudo transver-sal, a partir de uma coorte prospectiva, com 60 pacientes atendidos na atenção primá-ria à saúde no município de Ijuí, utilizando-se questionário para verificar o nível de informação prestada aos pacientes pela equipe de sáude, a Escala de Adesão Terapêu-tica de Morisky de Oito Itens para verificar a adesão, e o exame do tempo de protrom-bina para verificar o valor INR. De acordo com os critérios adotados, verificou-se um nível insuficiente de informações prestada pela equipe de saúde, baixa adesão ao tra-tamento, com a maioria dos pacientes fora do intervalo terapêutico adequado. Verifica-se a necessidade de melhoria da qualidade das informações prestadas aos usuários, incentivo da adesão ao tratamento e melhor monitoramento da anticoagulação visando à segurança do paciente. / Warfarin is the oral anticoagulant most frequently prescribed, although is difficult handling warfarin in clinical practice. It’s has a well-established efficacy, but is con-sidered a potentially dangerous drug, and in primary health care is associated with fatal medication errors. To ensure patient safety, its use requires requires anticoagulation levels monitoring ,, so medication adherence and care information’s about anticoagula-tion therapy are important. The aim of this study was to verify the information level about the prescription, information level provided by the health care team, medication adherence and anticoagulation control levels by the International Normalized Ratio (INR) value. A cross-sectional study, from a prospective cohort, was realized with 60 patients seen in primary health care in Ijuí city, a questionnaire was use to check the information level to the patients by the health team, Eight Item Morisky Medication Adherence Scale was use to verify adherence, and prothrombin time exam was use to check the INR value. According to the criteria adopted, was observed insufficient in-formation level provided by health care team, poor adherence to treatment and most patients was out of the therapeutic range. It’s necessary improve the quality of infor-mation provided to the patients, promote medication adherence and improve the anti-coagulation monitoring for patient safety in the treatment.