BACKGROUND: The European Union (EU)(7)-PIM (potentially inappropriate medication) list presents the most comprehensive and up-to-date tool for evaluation of PIM prescribing in Europe; however, several country-specific studies have documented lower specificity of this list on pharmaceutical markets of some countries. The aim of our study was to describe approval rates and marketing of PIMs stated by EU(7)-PIM criteria in six EU countries [in comparison with the American Geriatric Society (AGS) Beers 2015 criteria]. METHODS: Research teams of six EU countries (Czech Republic, Spain, Portugal, Serbia, Hungary and Turkey) participated in this study conducted by WG1b EU COST Action IS1402 group in the period October 2015-November 2018. Data on approval rates of PIMs and their availability on pharmaceutical markets have been obtained from databases of national drug-regulatory institutes and up-to-date drug compendia. The EU(7)-PIM list and AGS Beers 2015 Criteria (Section 1) were applied. RESULTS: PIMs from EU(7)-PIM list were approved for clinical use more often than those from the AGS Beers 2015 criteria (Section 1). Approval rates for EU(7)-PIMs ranged from 42.8% in Serbia to 71.4% in Spain (for AGS criteria only from 36.4% to 65.1%, respectively). Higher percentages of approved PIMs were documented in Spain (71.4%), Portugal (67.1%) and Turkey (67.5%), lower in Hungary (55.5%), Czech Republic (50.2%) and Serbia (42.8%). The majority of approved PIMs were also currently marketed in all countries except in Turkey (19.8-21.7% not marketed PIMs) and less than 20% of PIMs were available as over-the-counter medications (except in Turkey, 46.4-48.1%). CONCLUSIONS: The EU(7)-PIM list was created for utilization in European studies; however, applicability of this list is still limited in some countries, particularly in Eastern and Central Europe. The EU project EUROAGEISM H2020 (2017-2021) that focuses on PIM prescribing and regulatory measures in Central and Eastern European countries must consider these limits.

Department of Clinical Pharmacy University of Szeged Szeged Hungary

Department of Environmental Health Portuguese National Institute of Health Porto Portugal

Department of Medical Biology Yeditepe University Istanbul Turkey

Department of Social and Clinical Pharmacy Charles University Czech Republic

Department of Social and Clinical Pharmacy Faculty of Pharmacy in Hradec Králové Charles University Heyrovského 1203 Hradec Králové 500 05 Czech Republic

Department of Social Pharmacy and Pharmaceutical Legislation University of Belgrade Belgrade Serbia

Department of Statistical Modeling The Czech Academy of Sciences Prague Czech Republic

DICOMOSA Group Department of Psychology Universidade da Coruña A Coruña Spain

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Reeve E, Gnjidic D, Long J, et al. A systematic review of the emerging definition of ‘deprescribing’ with network analysis: implications for future research and clinical practice. Br J Clin Pharmacol 2015; 80: 1254–1268. PubMed PMC

Scott I, Anderson K, Freeman C. Review of structured guides for deprescribing. Eur J Hosp Pharm Sci 2017; 24: 51. PubMed PMC

Beers MH, Ouslander JG, Rollingher I, et al. Explicit criteria for determining inappropriate medication use in nursing home residents. Arch Intern Med 1991; 151: 1825–1832. PubMed

American Geriatrics Society 2015 Beers Criteria Expert Panel. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2015; 63: 2227–2246. PubMed

American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019. Epub ahead of print 29 January 2019. DOI: 10.1111/jgs.15767. PubMed

O’Mahony D, O’Sullivan D, Byrne S, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing 2015; 44: 213–218. PubMed PMC

Renom-Guiteras A, Meyer G, Thürmann PA. The EU(7)-PIM list: a list of potentially inappropriate medications for older people consented by experts from seven European countries. Eur J Clin Pharmacol 2015; 71: 861–875. PubMed PMC

Laroche ML, Charmes JP, Merle L. Potentially inappropriate medications in the elderly: a French consensus panel list. Eur J Clin Pharmacol 2007; 63: 725–731. PubMed

Rognstad S, Brekke M, Fetveit A, et al. The Norwegian General Practice (NORGEP) criteria for assessing potentially inappropriate prescriptions to elderly patients. A modified Delphi study. Scand J Prim Health Care 2009; 27: 153–159. PubMed PMC

Nyborg G, Straand J, Klovning A, et al. The Norwegian General Practice – Nursing Home criteria (NORGEP-NH) for potentially inappropriate medication use: a web-based Delphi study. Scand J Prim Health Care 2015; 33: 134–141. PubMed PMC

Holt S, Schmiedl S, Thürmann PA. Potentially inappropriate medications in the elderly: the PRISCUS list. Dtsch Arztebl Int 2010; 107: 543–551. PubMed PMC

McLeod PJ, Huang AR, Tamblyn RM, et al. Defining inappropriate practices in prescribing for elderly people: a national consensus panel. CMAJ 1997; 156: 385–391. PubMed PMC

Rancourt C, Moisan J, Baillargeon L, et al. Potentially inappropriate prescriptions for older patients in long-term care. BMC Geriatr 2004; 4. PubMed PMC

Brown JD, Hutchison LC, Li C, et al. Predictive validity of the Beers and Screening tool of older persons’ potentially inappropriate prescriptions (STOPP) criteria to detect adverse drug events, hospitalizations, and emergency department visits in the United States. J Am Geriatr Soc 2016; 64: 22–30. PubMed PMC

Cahir C, Moriarty F, Teljeur C, et al. Potentially inappropriate prescribing and vulnerability and hospitalization in older community-dwelling patients. Ann Pharmacother 2014; 48: 1546–1554. PubMed

Tosato M, Landi F, Martone AM, et al. Potentially inappropriate drug use among hospitalised older adults: results from the CRIME study. Age Ageing 2014; 43: 767–773. PubMed

Landi F, Russo A, Liperoti R, et al. Impact of inappropriate drug use on physical performance among a frail elderly population living in the community. Eur J Clin Pharmacol 2007; 63: 791–799. PubMed

Poudel A, Peel NM, Nissen L, et al. Potentially inappropriate prescribing in older patients discharged from acute care hospitals to residential aged care facilities. Ann Pharmacother 2014; 48: 1425–1433. PubMed

Wallace E, McDowell R, Bennett K, et al. Impact of potentially inappropriate prescribing on adverse drug events, health related quality of life and emergency hospital attendance in older people attending general practice: a prospective cohort study. J Gerontol A Biol Sci Med Sci 2017; 72: 271–277. PubMed PMC

Morin L, Laroche ML, Texier G, et al. Prevalence of potentially inappropriate medication use in older adults living in nursing homes: a systematic review. J Am Med Dir Assoc 2016; 17: 862.e861–862.e869. PubMed

Tommelein E, Mehuys E, Petrovic M, et al. Potentially inappropriate prescribing in community-dwelling older people across Europe: a systematic literature review. Eur J Clin Pharmacol 2015; 71: 1415–1427. PubMed

Jiron M, Pate V, Hanson LC, et al. Trends in prevalence and determinants of potentially inappropriate prescribing in the United States: 2007 to 2012. J Am Geriatr Soc 2016; 64: 788–797. PubMed PMC

Moriarty F, Hardy C, Bennett K, et al. Trends and interaction of polypharmacy and potentially inappropriate prescribing in primary care over 15 years in Ireland: a repeated cross-sectional study. BMJ Open 2015; 5: e008656. PubMed PMC

Fialová D, Topinková E, Gambassi G, et al. Potentially inappropriate medication use among elderly home care patients in Europe. JAMA 2005; 293: 1348–1358. PubMed

European Medicines Agency. The European regulatory system for medicines and the European Medicines Agency. A consistent approach to medicines regulation across the European Union. EMA/437313/2014. European Medicines Agency, http://www.ema.europa.eu/docs/en_GB/document_library/Brochure/2014/08/WC500171674.pdf (2019, accessed 14 March).

European Commission. Regulation (EC) no. 726/2004 of the European parliament and of the council laying down community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, http://ec.europa.eu/health/files/eudralex/vol-1/reg_2004_726/reg_2004_726_en.pdf (2018, accessed 11 March).

European Medicines Agency. Human medicines research and development support. European Medicines Agency pre-authorisation procedural advice for users of the centralised procedure. EMA/339324/2007, http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004069.pdf (2019, accessed 11 March).

Wauters M, Elseviers M, Azermai M, et al. Availability and actual use in the Belgian market of potentially inappropriate medications (PIMs) from the EU(7)-PIM list. Eur J Clin Pharmacol 2016; 72: 243–245. PubMed

COST Action IS1402 on Ageism. COST Action IS1402 on Ageism - home page, http://notoageism.com/,(accessed 10 July 2018).

EuroAgeism Horizon 2020 Project. EuroAgeism Horizon 2020 project - home page, http://euroageism.eu/ (accessed 20 November 2018).

GEMAŞ Genel Mühendislik Mekanik San. ve Tic. AŞ RxMediaPharma, http://eczanet.com/kurulum.html (accessed 20 November 2018).

General Council of Official Associations of Pharmacists. Bot PLUS WEB, https://botplusweb.portalfarma.com/ (accessed 20 November 2018).

Medicines Catalog, Madrid, Spain, 2018. General Council of Official Associations of Pharmacists.

INFARMED: National Authority of Medicines and Health Products IP. INFARMED: National Authority of Medicines and Health Products IP, home page, http://www.infarmed.pt/web/infarmed-en/ (accessed 1 December 2018).

INFARMED - National Authority of Medicines and Health Products IP. Infomed - medicines database, http://app7.infarmed.pt/infomed/ (accessed 29 November 2018).

Medicines and Medical Devices Agency of Serbia. Search - human medicines, https://www.alims.gov.rs/latin/lekovi/pretrazivanje-humanih-lekova/ (accessed 1 December 2018).

Medicines and Medical Devices Agency of Serbia. National Medicines Registry - NRL 2016 Belgrade, Serbia, 2016.

National Health Insurance Fund of Hungary. National Health Insurance Fund of Hungary - home page, http://neak.gov.hu/ (accessed 25 November 2018).

National Health Insurance Fund of the Republic of Serbia. National Health Insurance Fund of the Republic of Serbia, home page, http://www.eng.rfzo.rs/index.php/aboutus(accessed 27 November 2018).

National Institute of Pharmacy and Nutrition. National Institute of Pharmacy and Nutrition - home page, http://ogyei.gov.hu (accessed 29 November 2018).

Spanish Agency of Medicines and Sanitary Products. Center of online information on medicines, https://cima.aemps.es/cima/publico/home.html (accessed 27 November 2018).

State Institute for Drug Control. State Institute for Drug Control, home page, http://www.sukl.eu/ (accessed 25 November 2018).

Turkish Medicines and Medical Devices Agency. Turkish Medicines and Medical Devices Agency (TMMDA), home page, https://www.titck.gov.tr/ (accessed November 27 2018).

European Statistical System. Census data, home page, https://ec.europa.eu/CensusHub2/query.do?step=selectHyperCube&countrycode=en&clearSession=true (accessed 12 December 2018).

Statistical Office of the Republic of Serbia. Age and sex data by settlements, home page, http://www.stat.gov.rs/en-US/oblasti/popis/popis-2011/popisni-podaci-eksel-tabele (accessed 12 December 2018).

Turkish Statistical Institute. Population censuses, home page. http://www.turkstat.gov.tr/VeriBilgi.do?alt_id=1047 (accessed 12 December 2018).

Cerveny R, Topinkova E. Recommended diagnostic and therapeutic procedures for general practitioners – Geriatrics. http://www.svl.cz/files/files/Doporucene-postupy-od-2013/DP-Geriatrie-2014.pdf (accessed 07 December 2018).

Health Office, Madrid Autonomous Community Government. Potentially inappropriate medications in older people, http://www.madrid.org/cs/Satellite?blobcol=urldata&blobheader=application%2Fpdf&blobheadername1=Content-Disposition&blobheadervalue1=filename%3DMPI+Presentaci%C3%B3n.pdf&blobkey=id&blobtable=MungoBlobs&blobwhere=1352861934227&ssbinary=true (accessed 9 December 2018).

Health and Consumer Department, Basque Country Autonomous Community Government. Pharmacotherapeutic guide for geriatric patients, http://www.osakidetza.euskadi.eus/contenidos/informacion/publicaciones_informes_estudio/es_pub/adjuntos/guia_pacientes_geriatricos.pdf (accessed 9 December 2018).

Turkish Medicines and Medical Devices Agency. Rational drug use in older patients, http://www.akilciilac.gov.tr/?page_id=767 (accessed 1 December 2018).

Ministry of Health, Turkish Medicines and Medical Devices Agency. Report from the workshop: current problems and solutions for drug use in elderly, http://www.akilciilac.gov.tr/wp-content/uploads/2015/12/Geriatri-Rapor-Son.pdf (accessed 1 December 2018).

Muhlack DC, Hoppe LK, Stock C, et al. The associations of geriatric syndromes and other patient characteristics with the current and future use of potentially inappropriate medications in a large cohort study. Eur J Clin Pharmacol 2018; 74: 1633–1644. PubMed

Grina D, Briedis V. The use of potentially inappropriate medications among the Lithuanian elderly according to Beers and EU(7)-PIM list – a nationwide cross-sectional study on reimbursement claims data. J Clin Pharm Ther 2017; 42: 195–200. PubMed

Çibik B, Şahin EM, Kilinçarslan MG. A population-based study: the appropriateness of drug use in the elderly according to Beers criteria. Turk Geriatri Dergisi 2018; 21: 1–15.

Öztürk GZ, Ardiç C, Toprak D. Frequency of polypharmacy and use of potentially inappropriate medications in the elderly. Turk Geriatri Dergisi 2017; 20: 296–305.

Gutiérrez-Valencia M, Izquierdo M, Malafarina V, et al. Impact of hospitalization in an acute geriatric unit on polypharmacy and potentially inappropriate prescriptions: a retrospective study. Geriatr Gerontol Int 2017; 17: 2354–2360. PubMed

Oner ZG, Michel SLJ, Polli JE. Equivalence and regulatory approaches of nonbiological complex drug products across the United States, the European Union, and Turkey. Ann N Y Acad Sci 2017; 1407: 26–38. PubMed

Mucalo I, Hadžiabdić MO, Brajković A, et al. Potentially inappropriate medicines in elderly hospitalised patients according to the EU(7)-PIM list, STOPP version 2 criteria and comprehensive protocol. Eur J Clin Pharmacol 2017; 73: 991–999. PubMed

Steinman MA, Beizer JL, Dubeau CE, et al. How to use the American Geriatrics Society 2015 Beers criteria - a guide for patients, clinicians, health systems, and payors. J Am Geriatr Soc 2015; 63: e1–e7. PubMed PMC

Ivanova I, Elseviers M, Wauters M, et al. European repository of explicit criteria of potentially inappropriate medications in old age. Geriatr Gerontol Int 6018; 18: 1293–1297. PubMed

Gallagher P, Lang PO, Cherubini A, et al. Prevalence of potentially inappropriate prescribing in an acutely ill population of older patients admitted to six European hospitals. Eur J Clin Pharmacol 2011; 67: 1175–1188. PubMed

Bor A, Matuz M, Csatordai M, et al. Medication use and risk of falls among nursing home residents: a retrospective cohort study. Int J Clin Pharm 2017; 39: 408–415. PubMed

Kovačević SV, Simišić M, Rudinski SS, et al. Potentially inappropriate prescribing in older primary care patients. PLoS One 2014; 9. PubMed PMC

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