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PLoS One ; 16(2): e0246426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33606722


BACKGROUND: Although tramadol is an effective weak opioid analgesic, careful monitoring of potential central nervous system adverse reactions in older adults is needed, especially when used with concomitant medications which may trigger the adverse effects. We aimed to characterize tramadol users with potentially inappropriate co-medications in older adults using a latent class analysis (LCA). METHOD: Patients aged 65 years or older using tramadol and receiving potentially inappropriate co-medications were included from a nationwide healthcare claims database. We defined antidepressants, first-generation antihistamines, and anxiolytics as potentially inappropriate co-medications. We applied an LCA for grouping tramadol users based on the common characteristics of medication use and healthcare utilization, and each patient was probabilistically assigned to a class. Patients' characteristics in different latent classes were compared. Potential adverse drug reactions (ADRs) was defined as the any visits for emergency department after the occurrence of potentially inappropriate co-medications. Logistic regression analysis was used to examine the association between latent classes and potential ADRs. RESULTS: We identified four distinct latent classes of tramadol users representing different patterns of co-medications: multiple potential drug-drug interaction (pDDI) combination users, antihistamines-tramadol users, antidepressants-tramadol users, and anxiolytics-tramadol users. Multiple pDDI combination users showed high proportion of regular tramadol use, tended to visit more medical institutions, and had a high Charlson comorbidity score. The duration of use of potentially inappropriate co-medications with tramadol was the longest in multiple pDDI combination users and the shortest in antihistamines-tramadol users. When compared with antihistamines-tramadol users, increased potential ADR risk was observed in multiple pDDI combination users (adjusted odds ratio (OR), 1.81; 95% confidence interval (CI), 1.75-1.88), antidepressants-tramadol users (1.24; 1.19-1.29), and anxiolytics-tramadol users (1.04; 1.00-1.08). CONCLUSIONS: Four distinct classes were identified among older adults using tramadol and potentially inappropriate co-medications. Differences in potential ADR risk were observed between these classes. These findings may help to identify patients at a high risk for ADRs owing to potentially inappropriate co-medications with tramadol.

Yonsei Med J ; 61(9): 741-749, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882758


PURPOSE: Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used in patients with atrial fibrillation (AF) because of their effectiveness in preventing stroke and their better safety, compared with warfarin. However, there are concerns for an increased risk of bleeding associated with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective serotonin reuptake inhibitors (SSRIs) with NOACs. In this study, we aimed to evaluate the risk of bleeding events in individuals taking concomitant NSAIDs or SSRIs with NOACs after being diagnosed with AF. MATERIALS AND METHODS: A nested case-control analysis to assess the safety of NSAIDs and SSRIs among NOAC users with AF was performed using data from Korean National Health Insurance Service from January 2012 to December 2017. Among patients who were newly prescribed NOACs, 1233 cases hospitalized for bleeding events were selected, and 24660 controls were determined. RESULTS: The risk of bleeding events was higher in patients receiving concomitant NSAIDs [adjusted odds ratio (aOR) 1.41; 95% confidence interval (CI) 1.24-1.61] or SSRIs (aOR 1.92; 95% CI 1.52-2.42) with NOACs, compared to no use of either drug, respectively. The risk of upper gastrointestinal bleeding was higher in patients receiving concomitant NSAIDs or SSRIs without proton pump inhibitors (PPIs) (NSAIDs: aOR 2.47; 95% CI 1.26-4.83, SSRI: aOR 10.8; 95% CI 2.41-2.48) compared to no use. CONCLUSION: When NSAIDs or SSRIs are required for NOAC users with AF, physicians need to monitor bleeding events and consider the use of PPIs, especially for combined use of both drugs or when initiating NOACs treatment.

Anti-Inflamatórios não Esteroides/uso terapêutico , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/prevenção & controle , Hemorragia/prevenção & controle , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Administração Oral , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Fibrilação Atrial/complicações , Estudos de Casos e Controles , Feminino , Hemorragia Gastrointestinal/complicações , Hemorragia/epidemiologia , Humanos , Pessoa de Meia-Idade , Inibidores de Captação de Serotonina/efeitos adversos , Acidente Vascular Cerebral/etiologia
Basic Clin Pharmacol Toxicol ; 126(3): 226-235, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31520564


Tramadol is a weak opioid that is commonly used for chronic low back pain (LBP). Despite its effectiveness, duplicated use of tramadol, which may indicate abuse or dependence, may exacerbate potential adverse reactions. This population-based, cross-sectional study aimed to investigate the prevalence of duplication of tramadol and its associated factors among patients with LBP. From a Korean nationwide claims database, non-hospitalized patients aged 40-99 years with LBP without malignancy were prescribed tramadol during 2014-2016. Duplication of tramadol was defined as overlapping of prescription days. Among them, we defined "extensive duplication (ED)" when days of tramadol duplication cover 10% or more of the days prescribed tramadol. Patient and healthcare utilization factors associated with ED were examined using a logistic regression model. The study population was 6 417 503 patients. Of these, 13.7% were ED users. The age- and sex-standardized prevalence of using tramadol twice or more a year was 14.06 per 100 people in 2014, 13.74 per 100 people in 2015 and 13.52 per 100 people in 2016. ED occurred more in those in the group aged 70-79 years (OR 1.12, 95% CI 1.11-1.13) than 40-49 years and in those with comorbidities, such as drug abuse (OR 2.99, 95% CI 2.05-4.36) or depression (OR 1.75, 95% CI 1.72-1.77). Based on the results of this study, a proper management system is needed to avoid tramadol duplication among older people and patients with drug abuse or depression.

Analgésicos Opioides/administração & dosagem , Dor Crônica/tratamento farmacológico , Dor Lombar/tratamento farmacológico , Tramadol/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Estudos Transversais , Bases de Dados Factuais , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , República da Coreia , Tramadol/efeitos adversos