RESUMO
Model-informed precision dosing (MIPD) has become synonymous with modern approaches for individualizing drug therapy, in which the characteristics of each patient are considered as opposed to applying a one-size-fits-all alternative. This review provides a brief account of the current knowledge, practices, and opinions on MIPD while defining an achievable vision for MIPD in clinical care based on available evidence. We begin with a historical perspective on variability in dose requirements and then discuss technical aspects of MIPD, including the need for clinical decision support tools, practical validation, and implementation of MIPD in health care. We also discuss novel ways to characterize patient variability beyond the common perceptions of genetic control. Finally, we address current debates on MIPD from the perspectives of the new drug development, health economics, and drug regulations.
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Desenvolvimento de Medicamentos , HumanosRESUMO
PURPOSE: The purpose of this study was to investigate the prevalence of prescribed combinations of interacting drugs in the Swedish population. METHODS: This study design was retrospective and cross-sectional, based on a national register of dispensed prescription drugs during the period from January 1 to April 30, 2010. Prescription data was linked to the drug-drug interaction database SFINX to yield the prevalence of interacting combinations dispensed in the population. The study focused in particular on C- (clinically relevant interactions that can be handled, e.g. by dose adjustments), and D-interactions (clinically relevant interactions that should be avoided). RESULTS: Thirty-eight and 3.8 % of the population were dispensed combinations of drugs classified as C- or D- interactions, respectively, i.e. clinically relevant, involving all therapeutic areas. Half of the D-interactions were associated with increased risk of adverse drug reactions whereas the other half were considered interactions with a potential to cause therapeutic failure. We identified a top 15 list of D-interactions that included 80 % of the total number of interacting drug combinations. Regarding individual drugs, a group of only ten drugs was involved in as much as 94 % of all D-interactions. CONCLUSIONS: This study reveals that the majority of prescribed interacting drug combinations in Sweden involve a limited number of drugs. The findings may increase the awareness among prescribers of these most common drug interactions in clinical practice and highlight an area for pharmacological education. It may also serve as an inventory of potential interactions within different therapeutic areas for further research.
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Interações Medicamentosas , Prescrições de Medicamentos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Suécia/epidemiologia , Adulto JovemRESUMO
PURPOSE: To present concept, methods and use of a knowledge database providing assessments of potential fetal risks for all drugs on the Swedish market. METHODS: Assessments of fetal risks are made primarily by analyzing prospective epidemiological data from the Swedish Medical Birth Register on drug intake in relation to birth outcome. This is complemented by evaluation of the scientific literature. Following standardized working procedures, a statement is compiled for each substance, which is also classified into one of three categories depending on the estimated risk level. The final documents include drug product names on the market, via linkage to a medicinal products register. The information is free and published on the website www.janusinfo.se . It can also be used as an integrated part of electronic health records. RESULTS: The database covers assessments of fetal risks for close to 1,250 medicinal drug substances on the Swedish market. Each year, 96,000 searches are made, which might be compared to the around 100,000 children born in Sweden yearly. Apart from the Swedish Physicians' Desk Reference (Fass), the database is the most commonly used resource among specialists within gynaecology and perinatal medicine for information on drugs during pregnancy. CONCLUSIONS: A non-commercial knowledge base with assessments of fetal risk of different drugs is valued by health care professionals and is used extensively in Sweden. Based on analyses of national health registers, the database provides unique information on teratogenic drug risks.
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Anormalidades Induzidas por Medicamentos , Sistemas de Notificação de Reações Adversas a Medicamentos , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Sistema de Registros , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Sistemas de Notificação de Reações Adversas a Medicamentos/organização & administração , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Gravidez , Sistema de Registros/estatística & dados numéricos , Medição de Risco , SuéciaRESUMO
BACKGROUND: Clinical decision support (CDS) for electronic prescribing systems (computerized physician order entry) should help prescribers in the safe and rational use of medicines. However, the best ways to alert users to unsafe or irrational prescribing are uncertain. Specifically, CDS systems may generate too many alerts, producing unwelcome distractions for prescribers, or too few alerts running the risk of overlooking possible harms. Obtaining the right balance of alerting to adequately improve patient safety should be a priority. METHODS: A workshop funded through the European Regional Development Fund was convened by the University Hospitals Birmingham NHS Foundation Trust to assess current knowledge on alerts in CDS and to reach a consensus on a future research agenda on this topic. Leading European researchers in CDS and alerts in electronic prescribing systems were invited to the workshop. RESULTS: We identified important knowledge gaps and suggest research priorities including (1) the need to determine the optimal sensitivity and specificity of alerts; (2) whether adaptation to the environment or characteristics of the user may improve alerts; and (3) whether modifying the timing and number of alerts will lead to improvements. We have also discussed the challenges and benefits of using naturalistic or experimental studies in the evaluation of alerts and suggested appropriate outcome measures. CONCLUSIONS: We have identified critical problems in CDS, which should help to guide priorities in research to evaluate alerts. It is hoped that this will spark the next generation of novel research from which practical steps can be taken to implement changes to CDS systems that will ultimately reduce alert fatigue and improve the design of future systems.
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Sistemas de Apoio a Decisões Clínicas/normas , Prescrição Eletrônica/normas , Sistemas de Registro de Ordens Médicas/normas , Europa (Continente) , Humanos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Discrepancies in medication lists are common and can contribute to drug-related problems. This study was performed before the implementation of the National Medication List in Sweden, an intervention expected to improve the accuracy of medication lists. AIM: The aim of the study was to examine the number and type of discrepancies in the medication list from pharmacies in Sweden. The secondary aim was to describe the information sources Swedish patients used as their medication lists and how confident they were with the information. METHOD: Structured interviews were conducted with patients at 13 community pharmacies in Sweden during the period October 5, 2020, to April 16, 2021. The printed medication list was reviewed together with the patient to identify any discrepancies and missing information. RESULTS: A total of 327 patients were included in the study (response rate 51%). The printed medication list from pharmacies was the most common information source for patients to know which medications to use. Two thirds (n = 215) of the patients had at least one discrepancy among their prescriptions and 32% (n = 106) were missing at least one prescription medication. Among all prescriptions (n = 2567) 10% (n = 264) were non-current prescriptions, 9% (n = 238) were duplicates and 3% (n = 88) had the wrong dose. The proportion of prescriptions with discrepancies differed between drug-groups. CONCLUSION: The discrepancies described in this study can have serious consequences, and results provide a baseline for studies after the implementation of the National Medication List.
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Farmácias , Humanos , Suécia , Prescrições , Pacientes , Pesquisa Qualitativa , Reconciliação de MedicamentosRESUMO
AIMS: Relevant and easily accessible drug information at point-of-care is essential for physicians' decision making when prescribing. However, the information available by using Clinical Decision Support Systems (CDSSs) often does not meet physicians' requirements. The Summary of Product Characteristics (SmPC) is statutory information about drugs. However, the current structure, content and format of SmPCs make it difficult to incorporate them into CDSSs and link them to relevant patient information from the Electronic Health Records. The aim of the study was to evaluate the perceived needs for drug information among physicians in Sweden. METHODS: We recruited three focus group discussions with 18 physicians covering different specialities. The information from the groups was combined with a questionnaire administered at the beginning of the group discussions. RESULTS: Physicians reported their needs for knowledge databases at the point of drug prescribing. This included more consistent information about existing and new drugs. They also wished to receive automatically generated alerts for severe drug-drug interactions and adverse effects, and to have functions for calculating glomerular filtration rate to enable appropriate dose adjustments to be made for elderly patients and those with impaired renal function. Additionally, features enhancing electronic communication with colleagues and making drug information more searchable were suggested. CONCLUSIONS: The results from the current study showed the need for knowledge databases which provide consistent information about new and existing drugs. Most of the required information from physicians appeared to be possible to transfer from current SmPCs to CDSSs. However, inconsistencies in the SmPC information have to be reduced to enhance their utility.
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Sistemas de Apoio a Decisões Clínicas/normas , Serviços de Informação sobre Medicamentos/normas , Informática Médica/métodos , Médicos/psicologia , Sistemas Automatizados de Assistência Junto ao Leito , Adulto , Grupos Focais , Humanos , Masculino , Informática Médica/normas , Pessoa de Meia-Idade , Médicos/estatística & dados numéricos , Atenção Primária à Saúde , Inquéritos e Questionários , SuéciaRESUMO
Skewed information about medicines in social media influence the healthcare-patient contact. Healthcare staff need situation adapted evidence that can be linked to patient data. For 20 years Sweden has provided praised Pharmacological Knowledge Bases (PKB). They include ¼Janusmed drug-drug interactions«, ¼Janusmed drugs and birth defects« and ¼e-Ped (electronic pediatric) instructions and drug dosage control«. PKBs need to be better integrated into digital tools adhering to a national guide for optimal interface presentation of information. They should be produced by medical editors and delivered through a national digital highway. Experts need to adhere to a policy for handling conflicts of interest and evaluate that information is appreciated and used. PKBs should be accessible as a public good for healthcare staff, students and the public to support personalized medical care.
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Bases de Conhecimento , Mídias Sociais , Criança , Atenção à Saúde , Humanos , SuéciaRESUMO
Adverse drug reactions (ADRs) for all drugs in Europe are described in the legally approved Summary of Product Characteristics (SmPC). An overview of all ADRs of the patients' drug list can support healthcare staff to link patient symptoms to possible ADRs. We review the possibilities and challenges to extract ADR information from SmPCs and present the development of our semi-automated procedure for extraction of ADRs from the tabulated section of the SmPCs to create a database, named Bikt, which is regularly updated and used at point of care in Sweden. The existence of five major table formats for ADRs used in the SmPCs required the development of different parsing scripts. Manual checks for correctness for all content has to be performed. The quality of extraction was investigated for all SmPCs by measuring precision, recall and F1 scores (i.e. the weighted harmonic mean of precision and recall) and compared with other methods published. We conclude that it is possible to semi-automatically extract ADR information from SmPCs. However, clear technical and content guidelines and standards for ADR tables and terms from drug registration authorities would lead to improved extraction and usability of ADR information at point of care.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Europa (Continente) , HumanosRESUMO
Adverse drug reactions (ADRs) for all drugs in Europe are described in the legally approved Summary of Product Characteristics (SmPC). An overview of all ADRs of the patients' drug list can support healthcare staff to link patient symptoms to possible ADRs. We review the possibilities and challenges to extract ADR information from SmPCs or American Structured Product Labels and present the development of our semi-automated procedure for extraction of ADRs from the tabulated section in the SmPCs to create a database, named Bikt, which is regularly updated and used at point of care in Sweden. The existence of five major table formats for ADRs used in the SmPCs required the development of different parsing scripts. Manual checks for correctness for all content have to be performed. The quality of extraction was investigated for all SmPCs by measuring precision, recall and F1 scores and compared with other methods published. We conclude that it is possible to semi-automatically extract ADR information from SmPCs. However, clear technical and content guidelines and standards for ADR tables and terms from drug registration authorities would lead to improved extraction and usability of ADR information at point of care.
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Sistemas de Notificação de Reações Adversas a Medicamentos/organização & administração , Rotulagem de Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito/organização & administração , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Europa (Continente) , Humanos , Sistemas Automatizados de Assistência Junto ao Leito/estatística & dados numéricosRESUMO
INTRODUCTION: Technical and logical breakthroughs have provided new opportunities in medicine to use knowledge bases and large-scale clinical data (real-world) at point-of-care as part of a learning healthcare system to diminish the knowledge-practice gap. AREAS COVERED: The article is based on presentations, discussions and recommendations from an international scientific workshop. Value, research needs and funding avenues of knowledge bases and access to real-world data as well as transparency and incorporation of patient perspectives are discussed. EXPERT OPINION: Evidence-based, publicly funded, well-structured and curated knowledge bases are of global importance. They ought to be considered as a public responsibility requiring transparency and handling of conflicts of interest. Information has to be made accessible for clinical decision support systems (CDSS) for healthcare staff and patients. Access to rich and real-world data is essential for a learning health care ecosystem and can be augmented by data on patient-reported outcomes and preferences. This field can progress by the establishment of an international policy group for developing a best practice guideline on the development, maintenance, governance, evaluation principles and financing of open-source knowledge bases and handling of real-world data.
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Sistemas de Apoio a Decisões Clínicas , Atenção à Saúde/organização & administração , Medicina Baseada em Evidências/normas , Bases de Conhecimento , Atenção à Saúde/normas , Humanos , Internacionalidade , Medidas de Resultados Relatados pelo Paciente , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVE: The aim was to develop a drug-drug interaction database (SFINX) to be integrated into decision support systems or to be used in website solutions for clinical evaluation of interactions. METHODS: Key elements such as substance properties and names, drug formulations, text structures and references were defined before development of the database. Standard operating procedures for literature searches, text writing rules and a classification system for clinical relevance and documentation level were determined. ATC codes, CAS numbers and country-specific codes for substances were identified and quality assured to ensure safe integration of SFINX into other data systems. Much effort was put into giving short and practical advice regarding clinically relevant drug-drug interactions. RESULTS: SFINX includes over 8,000 interaction pairs and is integrated into Swedish and Finnish computerised decision support systems. Over 31,000 physicians and pharmacists are receiving interaction alerts through SFINX. User feedback is collected for continuous improvement of the content. CONCLUSION: SFINX is a potentially valuable tool delivering instant information on drug interactions during prescribing and dispensing.
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Sistemas de Gerenciamento de Base de Dados , Sistemas de Apoio a Decisões Clínicas , Interações MedicamentosasRESUMO
PURPOSE: To describe the occurrence of potential drug-drug interactions (DDIs) in prescribed drugs, dispensed to pediatric outpatients in Sweden. METHODS: A cross sectional study was conducted based on data from a national register of prescribed drugs, dispensed at pharmacies, to children 0-17 years old. The study period was January 1 to April 30, 2010. Drug dispensing data was linked to the DDI database SFINX. Prevalence and frequencies of potential interactions were investigated, and drugs commonly involved in interactions were identified. The study focused on clinically relevant potential interactions, class D (should be avoided), and class C (can be handled, e.g. by dose adjustment). RESULTS: In the Swedish pediatric population, 0 to 17 years of age, 12% (n = 231 078) of children had at least two dispensed drugs. In this group of patients, 0.14% had potential D-interactions and 1,3% had potential C-interactions. The number of D- and C-interactions that may lead to reduced effects were 181 (52%), and 1224 (32%) respectively. The ten most frequent drugs were involved in 78% and 65% of all potential D-, and C-interactions respectively. Furthermore, 80%, and 58% of the D-, and C-interactions respectively occurred in patients aged 12 to 17. CONCLUSIONS: We identified a limited number of drugs that were represented in the majority of potential interactions. Interactions that can lead to a reduced treatment effect constituted approximately half of D-interactions, and a third of C-interactions. The frequency of potential interactions was higher in older children. The results may contribute to increased prescriber awareness of important potential drug interactions among pediatric outpatients.
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Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pacientes Ambulatoriais , Prevalência , Suécia/epidemiologiaRESUMO
Drug-drug interactions are increasingly common, as patients are getting older and the number of drugs per patient is increasing. In this study, we investigated to which extent potential drug-drug interactions originated from single or multiple prescribers. All patients attending any of 20 primary healthcare centres were included in a retrospective observational cohort study. Data on all prescriptions to these patients, irrespectively of the prescriber, were collected for two 4-month periods. Potential drug interactions were identified using the drug-drug interaction database SFINX. Interactions were classified with respect to the workplace of the prescriber, and the prevalence of interactions according to origin was analysed. We found that the drug interactions were significantly more common when the drugs were prescribed from different healthcare centres, compared with drugs prescribed from the patients' primary healthcare centre only. One explanation for this increased risk of drug interactions could be that the prescribers at different primary healthcare centres do not share the same information concerning the total medication list of the patient.
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Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Medicamentos sob Prescrição/efeitos adversos , Atenção Primária à Saúde , Adulto , Idoso , Prescrições de Medicamentos , Revisão de Uso de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimedicação , Prevalência , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologia , Fatores de TempoRESUMO
INTRODUCTION: Stockholm County Council is the largest health care provider in Sweden with an annual budget of US$ 5 billion and catering the needs of a metropolitan population of 2 million people. About 10% of health care costs are used on drugs. In 1996 Stockholm County Council decided to address the main problems associated with the process and the quality of drug prescribing. METHODS: A multiyear strategy was designed, including the establishment of a strong evidence-based organisation, Drug and Therapeutics Committees and editorial resources to adapt information to the IT-media and the development of the IT-architecture. The development and implementation of computerized tools such as a physician drug order entry system including decision support, a drug information website and electronic transmission of prescriptions were started in 1996. RESULTS: The implementation was slow at the point-of-care units. It took about 6 years before the implementation process gained speed. In September 2005 almost 1000 doctors could use the decision support system for prescribing drugs and more than 70% of all prescriptions were transmitted electronically in our region. CONCLUSIONS: The work with the strategy has shown that improvements in drug use can be accomplished by providing access to simple, rapid and safe electronic tools, but the information provided has to be associated with well-recognized regional and national expert organisations.
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Atenção à Saúde , Difusão de Inovações , Conhecimentos, Atitudes e Prática em Saúde , Sistemas de Registro de Ordens Médicas , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Medicina Estatal , SuéciaRESUMO
In a recent Swedish register study, a limited number of specific drugs explained a large part of clinically relevant, potential drug-drug interactions (DDI), as defined and detected by the DDI database SFINX. Regarding interactions that should be avoided according to the definition in the database (class D), 15 drug combinations accounted for as much as 80 % of the prevalence in the Swedish population. Ten specific drugs were involved in 94 % of all detected class D interactions. About half of the clinically relevant interactions detected during the four-month study period were associated with an increased risk of adverse drug reactions, whereas the other half has a potential to cause therapeutic failure. An increased awareness among prescribers of these interacting drugs could contribute to safer and more effective drug use.
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Interações Medicamentosas , Fatores Etários , Bases de Dados Factuais , Sistemas de Apoio a Decisões Clínicas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Sistema de Registros , Fatores Sexuais , SuéciaRESUMO
BACKGROUND: Drug-related problems cause suffering for patients and substantial costs. Multi-dose drug dispensing is a service in which patients receive their medication packed in bags with one unit for each dose occasion. The electronic expert support system (EES) is a clinical decision support system that provides alerts if potential drug-related problems are detected among a patients' current prescriptions, including drug-drug interactions, therapy duplications, high doses, drug-disease interactions, drug gender warnings, and inappropriate drugs and doses for geriatric or pediatric patients. OBJECTIVE: The aim of the study was to explore physicians' views on the clinical relevance of alerts provided by EES. Furthermore we investigated if physicians performed any changes in drug treatment following the alerts and if there were any differences in perceived relevance and performed changes between different types of alerts and drugs. SETTING: Two geriatric clinics and three primary care units in Sweden. METHOD: Prescribed medications for patients (n = 254) with multi-dose drug dispensing were analyzed for potential drug-related problems using EES. For each alert, a physician assessed clinical relevance and indicated any intended action. A total of 15 physicians took part in the study. Changes in drug treatment following the alerts were later measured. The relationship between variables was analyzed using Chi square test. MAIN OUTCOME MEASURE: Physicians' perceived clinical relevance of each alert, and changes in drug treatment following the alerts. RESULTS: Physicians perceived 68% (502/740) of EES alerts as clinically relevant and 11% of all alerts were followed by a change in drug treatment. Clinical relevance and likelihood to make changes in drug treatment was related to the alert category and substances involved in the alert. CONCLUSION: In most patients with multi-dose drug dispensing, EES detected potential drug-related problems, with the majority of the alerts regarded as clinically relevant and some followed by measurable changes in drug treatment.
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Atitude do Pessoal de Saúde , Sistemas de Registro de Ordens Médicas , Erros de Medicação/prevenção & controle , Médicos/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , MasculinoRESUMO
PURPOSE: The aim of the present study was to investigate how prescribers and pharmacists use and perceive the drug-drug interaction database SFINX in their clinical work. METHODS: A questionnaire was developed with questions aimed at the usage of SFINX, and the perceptions of the database. The questionnaire was sent out to all registered users of the web application of SFINX. The anonymous answers from the target users, prescribers and pharmacists were summarized using descriptive statistics. Statistical analysis was performed on age and gender differences for some questions regarding different usage patterns. RESULTS: The questionnaire was sent to 11,763 registered SFINX users. The response rate was 23%, including 1871 answers from prescribers or pharmacists. SFINX was reported to be used at least weekly or more often by 45% of the prescribers and 51% of the pharmacists. Many prescribers reported using the database during the patient consultation (60%) or directly before or after (56%). Among the prescribers, 74% reported that the information received made them change their action at least sometimes. About 20% of the prescribers and 25% of the pharmacists considered the information as irrelevant sometimes or more often. CONCLUSION: Most prescribers and pharmacists reported using SFINX in direct association with a patient consultation. Information received by using SFINX makes prescribers and pharmacists change their handling of patients. DDI databases with relevant information about patient handling might improve drug treatment outcome.
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Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Atitude do Pessoal de Saúde , Bases de Dados Factuais/estatística & dados numéricos , Prescrições de Medicamentos/estatística & dados numéricos , Sistemas de Registro de Ordens Médicas/estatística & dados numéricos , Erros de Medicação/prevenção & controle , Adulto , Idoso , Feminino , Finlândia , Humanos , Masculino , Erros de Medicação/estatística & dados numéricos , Sistemas de Medicação no Hospital , Pessoa de Meia-Idade , Farmacêuticos/estatística & dados numéricos , Farmacovigilância , Médicos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Inquéritos e Questionários , SuéciaRESUMO
PURPOSE: To investigate the extent to which clinicians avoid well-established drug-drug interactions that cause statin-induced myopathy. We hypothesised that clinicians would avoid combining erythromycin or verapamil/diltiazem respectively with atorvastatin or simvastatin. In patients with statin-fibrate combination therapy, we hypothesised that gemfibrozil was avoided to the preference of bezafibrate or fenofibrate. When combined with verapamil/diltiazem or fibrates, we hypothesized that the dispensed doses of atorvastatin/simvastatin would be decreased. METHODS: Cross-sectional analysis of nationwide dispensing data. Odds ratios of interacting erythromycin, verapamil/diltiazem versus respective prevalence of comparator drugs doxycycline, amlodipine/felodipine in patients co-dispensed interacting statins simvastatin/atorvastatin versus patients unexposed (pravastatin/fluvastatin/rosuvastatin) was calculated. For fibrates, OR of gemfibrozil versus fenofibrate/bezafibrate in patients co-dispensed any statin was assessed. RESULTS: OR of interacting erythromycin versus comparator doxycycline did not differ between patients on interacting and comparator statins either in patients dispensed high or low statin doses (adjusted OR 0.87; 95% CI 0.60-1.25 and 0.92; 95% CI 0.69-1.23). Interacting statins were less common among patients dispensed verapamil/diltiazem as compared to patients on amlodipine/felodipine (OR high dose 0.62; CI 0.56-0.68 and low dose 0.63; CI 0.58-0.68). Patients on any statin were to a lesser extent dispensed gemfibrozil compared to patients not dispensed a statin (OR high dose 0.65; CI 0.55-0.76 and low dose 0.70; CI 0.63-0.78). Mean DDD (SD) for any statin was substantially higher in patients co-dispensed gemfibrozil 178 (149) compared to patients on statin monotherapy 127 (93), (p<0.001). CONCLUSIONS: Prescribers may to some extent avoid co-prescription of statins with calcium blockers and fibrates with an increased risk of myopathy. We found no evidence for avoiding co-prescriptions of statins and antibiotics with an increased risk of statin-induced adverse drug reactions. Co-prescription of statins and gemfibrozil is paradoxically associated with a marked increased statin dose, further aggravating the risk for severe myopathy.