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      The Prevalence of Selected Potential Drug-Drug Interactions of Analgesic Drugs and Possible Methods of Preventing Them: Lessons Learned From the Analysis of the Real-World National Database of 38 Million Citizens of Poland

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          Abstract

          Introduction: Drug-drug interactions may lead to poor health outcomes, as well as increased costs and utilization of healthcare services. Unfortunately, real-world data continuously prove high prevalence of potential drug-drug interactions (pDDIs) worldwide. Among identified drivers, ageing, multimorbidity and polypharmacy play a very important role. With these factors being widespread, the need for implementation of strategies minimizing the burden of pDDIs becomes an urgency. This, however, requires a better understanding of the prevalence of pDDIs and the underlying causative factors.

          Aim of study: To assess the real-world prevalence of pDDIs and its characteristics in the general population of Poland, using analgesic drugs as a model, and to find out whether pDDIs are caused by prescribing coming from the very same prescribers (co-prescribing).

          Methods: A retrospective analysis of the 2018 dispensation data of the National Health Fund (NHF) - the only Polish public healthcare payer organization with nationwide coverage. We searched for selected pDDIs of non-steroidal anti-inflammatory drugs (NSAIDs) with antihypertensives, other NSAIDs (double use), oral glucocorticoids, oral anticoagulants, selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and antiplatelet drugs; as well as opioides with SSRIs, SNRIs, gabapentinoids, and benzodiazepines. A pDDI was deemed present if two drugs standing in a possible conflict were dispensed within the same calendar month.

          Results: Out of 38.4 million citizens of Poland, 23.3 million were dispensed prescribed drugs reimbursed by NHF in 2018. In this cohort, we have identified 2,485,787 cases of analgesic drug pDDIs, corresponding with 6.47% of the Polish population. Out of these, the most prevalent pDDI was caused by “NSAIDs + antihypertensives” (1,583,575 cases, i.e., 4.12% of the Polish population), followed by “NSAIDs + NSAIDs” (538,640, 1.40%) and “NSAIDs + glucocorticoids” (213,504, 0.56%). The most persistent pDDIs among those studied were caused by “Opioids + Gabapentinoids” (2.19, 95%CI: 2.16–2.22 months). On average, 76.63% of all cases of pDDIs were caused by drugs prescribed by the very same prescribers.

          Conclusion: Based on high-quality, nationwide data, we have found a high prevalence of analgesic drugs-related pDDIs in Poland. Over ¾ of the identified pDDIs were caused by co-prescribing, i.e., prescriptions issued by the same prescribers. The significance of the problem, illustrated with our findings on analgesic drugs-related pDDIs in Poland, deserves much more scientific and policymaker attention.

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          Most cited references63

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          STOPP/START criteria for potentially inappropriate prescribing in older people: version 2

          Purpose: screening tool of older people's prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required. Methods: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology. Results: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines. Conclusion: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts.
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            What is polypharmacy? A systematic review of definitions

            Background Multimorbidity and the associated use of multiple medicines (polypharmacy), is common in the older population. Despite this, there is no consensus definition for polypharmacy. A systematic review was conducted to identify and summarise polypharmacy definitions in existing literature. Methods The reporting of this systematic review conforms to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. MEDLINE (Ovid), EMBASE and Cochrane were systematically searched, as well as grey literature, to identify articles which defined the term polypharmacy (without any limits on the types of definitions) and were in English, published between 1st January 2000 and 30th May 2016. Definitions were categorised as i. numerical only (using the number of medications to define polypharmacy), ii. numerical with an associated duration of therapy or healthcare setting (such as during hospital stay) or iii. Descriptive (using a brief description to define polypharmacy). Results A total of 1156 articles were identified and 110 articles met the inclusion criteria. Articles not only defined polypharmacy but associated terms such as minor and major polypharmacy. As a result, a total of 138 definitions of polypharmacy and associated terms were obtained. There were 111 numerical only definitions (80.4% of all definitions), 15 numerical definitions which incorporated a duration of therapy or healthcare setting (10.9%) and 12 descriptive definitions (8.7%). The most commonly reported definition of polypharmacy was the numerical definition of five or more medications daily (n = 51, 46.4% of articles), with definitions ranging from two or more to 11 or more medicines. Only 6.4% of articles classified the distinction between appropriate and inappropriate polypharmacy, using descriptive definitions to make this distinction. Conclusions Polypharmacy definitions were variable. Numerical definitions of polypharmacy did not account for specific comorbidities present and make it difficult to assess safety and appropriateness of therapy in the clinical setting.
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              The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995–2010

              Background The escalating use of prescribed drugs has increasingly raised concerns about polypharmacy. This study aims to examine changes in rates of polypharmacy and potentially serious drug-drug interactions in a stable geographical population between 1995 and 2010. Methods This is a repeated cross-sectional analysis of community-dispensed prescribing data for all 310,000 adults resident in the Tayside region of Scotland in 1995 and 2010. The number of drug classes dispensed and the number of potentially serious drug-drug interactions (DDIs) in the previous 84 days were calculated, and age-sex standardised rates in 1995 and 2010 compared. Patient characteristics associated with receipt of ≥10 drugs and with the presence of one or more DDIs were examined using multilevel logistic regression to account for clustering of patients within primary care practices. Results Between 1995 and 2010, the proportion of adults dispensed ≥5 drugs doubled to 20.8%, and the proportion dispensed ≥10 tripled to 5.8%. Receipt of ≥10 drugs was strongly associated with increasing age (20–29 years, 0.3%; ≥80 years, 24.0%; adjusted OR, 118.3; 95% CI, 99.5–140.7) but was also independently more common in people living in more deprived areas (adjusted OR most vs. least deprived quintile, 2.36; 95% CI, 2.22–2.51), and in people resident in a care home (adjusted OR, 2.88; 95% CI, 2.65–3.13). The proportion with potentially serious drug-drug interactions more than doubled to 13% of adults in 2010, and the number of drugs dispensed was the characteristic most strongly associated with this (10.9% if dispensed 2–4 drugs vs. 80.8% if dispensed ≥15 drugs; adjusted OR, 26.8; 95% CI 24.5–29.3). Conclusions Drug regimens are increasingly complex and potentially harmful, and people with polypharmacy need regular review and prescribing optimisation. Research is needed to better understand the impact of multiple interacting drugs as used in real-world practice and to evaluate the effect of medicine optimisation interventions on quality of life and mortality. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0322-7) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                18 January 2021
                2020
                : 11
                : 607852
                Affiliations
                [ 1 ]Department of Family Medicine, Medical University of Lodz, Łódź, Poland
                [ 2 ]National Health Fund, Warsaw, Poland
                [ 3 ]Department of Pharmacoeconomics, Institute of Mother and Child, Warsaw, Poland
                [ 4 ]Department of Internal Diseases, Asthma and Allergy, Medical University of Lodz, Łódź, Poland
                Author notes

                Edited by: Ugo Moretti, University of Verona, Italy

                Reviewed by: Janet Sultana, University of Messina, Italy

                Natasa Duborija-Kovacevic, University of Montenegro, Montenegro

                *Correspondence: Przemysław Kardas, pkardas@ 123456csk.am.lodz.pl

                This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology

                Article
                607852
                10.3389/fphar.2020.607852
                7849760
                33536918
                f613847f-4aa4-4b67-9494-8ddb3cbce895
                Copyright © 2021 Kardas, Urbański, Lichwierowicz, Chudzyńska, Czech, Makowska and Kardas.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 September 2020
                : 07 December 2020
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                drug – drug interactions,drug safety,inapropriate prescribing,pharmacoepidaemiology,real-world data,claim database,analgesic drugs,poland

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