Potentially inappropriate medications criteria-based tools for the elderly: a systematic scoping review Geovana Schiavo,1 Marcela Forgerini,1 Rosa Camila Lucchetta,1 Patricia de Carvalho Mastroianni.1
1 Department of Drugs and Medicines, Faculty of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil.
Corresponding author: Professora Dr. Patricia de Carvalho Mastroianni E-mail: [email protected] (+55 16) 3301-6977 Adjunct Professor, Department of Drugs and Medicines, Faculty of Pharmaceutical Sciences, São Paulo State University (UNESP) Highway Jaú, Km 01 s / n 14800-901, Araraquara SP- Brazil.
Summary Table 1. Search strategies in databases PubMed and Scopus...... 2 Figure 1. Selection process for review studies (adapted from PRISMA-ScR) - Potentially inappropriate medications tools in the elderly ...... 3 Figure 2. Selection process for review studies (adapted from PRISMA-ScR) - Potentially inappropriate drug interactions for elderly with respiratory diseases ...... 4 Figure 3. Selection process for review studies (adapted from PRISMA-ScR) - Potentially inappropriate drug interactions for elderly people with mental and behavioral disorders ...... 5 Table 2. Excluded records...... 6 Table 3. Commercialization and essentiality of potentially inappropriate medications for elderly...... 14 Table 4. Ten potentially inappropriate medication with a higher number of citations by tools, in decreasing order of citations...... 23 Table 5. Ten potentially inappropriate classes of medication with the highest number of citations by tools, in decreasing order...... 27 Table 6. Medication or pharmacological classes with the highest number of interactions...... 28 Table 7. Potentially inappropriate interactions between potentially inappropriate drugs and morbidities/syndromes classified according to the International Statistical Classification of Diseases and Related Health Problems – 10th revision...... 34 Table 8. Potentially inappropriate interaction (drug/pharmacological class), according three respiratory diseases classified according to the International Statistical Classification of Diseases and Related Health Problems – 10th revision...... 37 Table 9. Potentially inappropriate interaction (drug/pharmacological class), according six mental and behavioral disorders classified according to the International Statistical Classification of Diseases and Related Health Problems – 10th revision...... 38 Table 10. Reasons, therapeutic management for potentially inappropriate interaction (drug/pharmacological class), according six mental and behavioral disorders classified according to the International Statistical Classification of Diseases and Related Health Problems – 10th revision...... 40 Table 11. Potentially inappropriate medications with adverse drug reactions in the mental and behavioral disorders...... 47 References ...... 72
Table 1. Search strategies in databases PubMed and Scopus.
PUBMED #1 Population elderly[TIAB] OR aged[MH] OR aged[TIAB] OR “older adult*”[TIAB] OR “older people”[TIAB] OR geriatric[TIAB]
#2 Concept (((inappropriate[TIAB] OR appropriateness[TIAB]) AND (medication*[TIAB] OR prescri*[TIAB])) OR “inappropriate prescribing”[MH] OR “Potentially Inappropriate Medication List”[MH] OR Deprescriptions[MH] OR deprescription*[TIAB] OR “PIM”[TIAB])
#3 (tool[TIAB] OR criteria[TIAB] OR list[TIAB] OR consensus[TIAB] OR consensus[MH])
#4 Context (review[PT] OR meta-analysis[PT] OR news[PT] or letter[PT] OR editorial[PT] and types OR historical article[PT]) of studies
#5 Final ((#1 AND #2 AND #3) NOT #4) search strategy
SCOPUS #1 Population TITLE-ABS-KEY(elderly OR aged OR aged OR "older adult" OR "older adults" OR "older people" OR geriatric)
#2 Concept TITLE-ABS-KEY(((inappropriate OR appropriateness) AND (medication* OR prescri*)) OR "inappropriate prescribing" OR "Potentially Inappropriate Medication List" OR deprescription* OR PIM)
#3 TITLE-ABS-KEY(tool OR criteria OR list OR consensus)
#4 Context and types DOCTYPE ( bk OR ch OR cr OR ed OR le) of studies
#5 (INDEX(medline))
#6 Final search #1 AND #2 AND #3 AND NOT #4 AND NOT #5 strategy
Figure 1. Selection process for review studies (adapted from PRISMA-ScR) - Potentially inappropriate medications tools in the elderly
Database Manual search
(n = 2,467) (n = 10) Identification
Records after duplicates removed
(n = 2,370) Screening
Records screened (n = 2,380)
Records excluded (n = 2,273)
Eligibility Full-text articles assessed for eligibility (n = 107) Full-text articles excluded, with reasons
(n = 53)
Articles included in scoping
review Included (n = 54)
Figure 2. Selection process for review studies (adapted from PRISMA-ScR) - Potentially inappropriate drug interactions for elderly with respiratory diseases
Manual search Database (n = 10) (n = 2,467)
Identification
Records after duplicates removed
(n = 2,370)
Screening
Records screened (n = 2,380)
Records excluded (n = 2,273)
Eligibility Full-text articles assessed for eligibility (n = 107) Full-text articles excluded, with reasons
(n = 53) Articles included in scoping
review Included (n = 54) Full-text articles excluded
because do not include PIM or PII of respiratory diseases (n = 35) Articles included in respiratory analysis (n = 19)
PIM: potentially inappropriate medication; PII: potentially inappropriate interactions. Figure 3. Selection process for review studies (adapted from PRISMA-ScR) - Potentially inappropriate drug interactions for elderly people with mental and behavioral disorders
Database Manual search
2,467 (n = 10) Identification
Records after duplicates removed
(n = 2,370) Screening
Records screened (n = 2,379)
Records excluded (n = 2,273)
Eligibility Full-text articles assessed for eligibility (n = 107) Full-text articles excluded, with reasons
(n = 53)
Articles included in scoping
review Included (n = 54) Full-text articles excluded because do not include PIM
or PII of mental or behavior Articles included in mental disorders (n = 17) and behavior analysis (n = 37)
PIM: potentially inappropriate medication; PII: potentially inappropriate interactions.
Table 2. Excluded records.
Population 1. Nery, Raiany Thaimeny ;Reis, Adriano Max Moreira Development of a Brazilian anticholinergic activity drug scale 2019 Einstein (Sao Paulo, Brazil) 17 2 eAO4435-eAO 10.31744/einstein_journal/2019AO4435 Concept 2. Vrijkorte, Elze ;de Vries, Jennifer ;Schaafsma, Ron ;Wymenga, Machteld ;Oude Munnink, Thijs Optimising pharmacotherapy in older cancer patients with polypharmacy 2020 European journal of cancer care 29 1 e13185-e 10.1111/ecc.13185 3. Rodríguez-Pérez, A. ;Alfaro-Lara, E. R. ;Sierra-Torres, M. I. ;Villalba-Moreno, Á ;Nieto-Martin, M. D. ;Galván-Banqueri, M. ;Santos-Ramos, B. Validation of the LESS-CHRON criteria: Reliability study of a tool for deprescribing in patients with multimorbidity 2019 European Journal of Hospital Pharmacy 26 6 334-8 10.1136/ejhpharm-2017-001476 4. Rabenberg, Andree ;Schulte, Timo ;Hildebrandt, Helmut ;Wehling, Martin The FORTA (Fit fOR The Aged)-EPI (Epidemiological) Algorithm: Application of an Information Technology Tool for the Epidemiological Assessment of Drug Treatment in Older People 2019 Drugs & aging 36 10 969-78 10.1007/s40266-019- 00703-7 5. Kympers, C. ;Tommelein, E. ;Van Leeuwen, Ellen ;Boussery, K. ;Petrovic, M. ;Somers, A. Detection of potentially inappropriate prescribing in older patients with the GheOP³S-tool: completeness and clinical relevance 2019 Acta clinica Belgica 74 2 126-36 10.1080/17843286.2019.1568353 6. Jun, Kwanghee ;Hwang, Sunghee ;Ah, Young-Mi ;Suh, Yewon ;Lee, Ju-Yeun Development of an Anticholinergic Burden Scale specific for Korean older adults 2019 Geriatrics & gerontology international 19 7 628-34 10.1111/ggi.13680 7. Ivanova, Ivana ;Elseviers, Monique ;Wettermark, Bjorn ;Schmidt Mende, Katharina ;Vander Stichele, Robert ;Christiaens, Thierry Electronic assessment of cardiovascular potentially inappropriate medications in an administrative population database 2019 Basic & clinical pharmacology & toxicology 8. Updated criteria for inappropriate medication use in elderly persons 2004 Consultant 44 3 468-73 9. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults 2012 J Am Geriatr Soc 60 4 616-31 10.1111/j.1532-5415.2012.03923.x 10. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults 2015 J Am Geriatr Soc 63 11 2227-46 10.1111/jgs.13702 11. Azermai, M.; Vander Stichele, R. R.; Elseviers, M. M. Quality of pharmacotherapy in old age: focus on lists of Potentially Inappropriate Medications (PIMs) : Consensus statements from the European Science Foundation exploratory workshop 2016 Eur J Clin Pharmacol 72 7 897-904 10.1007/s00228-016-2051-z 12. Barry, P. J.; Gallagher, P.; Ryan, C.; O'Mahony, D. START (screening tool to alert doctors to the right treatment)--an evidence-based screening tool to detect prescribing omissions in elderly patients 2007 Age Ageing 36 6 632-8 10.1093/ageing/afm118 13. Beers, M. H. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update 1997 Arch Intern Med
157 14 1531-6
14. Beers, M. H.; Ouslander, J. G.; Rollingher, I.; Reuben, D. B.; Brooks, J.; Beck, J. C. Explicit criteria for determining inappropriate medication use in nursing home residents. UCLA Division of Geriatric Medicine 1991 Arch Intern Med 151 9 1825-32
15. Chang, C. B.; Yang, S. Y.; Lai, H. Y.; Wu, R. S.; Liu, H. C.; Hsu, H. Y.; Hwang, S. J.; Chan, D. C. Using published criteria to develop a list of potentially inappropriate medications for elderly patients in Taiwan 2012 Pharmacoepidemiol Drug Saf 21 12 1269-79 10.1002/pds.3274 16. Counsell, S. R. 2015 updated AGS Beers Criteria offer guide for safer medication use among older adults 2015 Geriatr Nurs 36 6 488-9
17. Dalleur, O.; Mouton, A.; Marien, S.; Boland, B. STOPP/START.v2: An uptodate tool for high-quality prescribing in older patients 2015 Louvain Medical 134 5 219-21
18. Delgado Silveira, E.; Munoz Garcia, M.; Montero Errasquin, B.; Sanchez Castellano, C.; Gallagher, P. F.; Cruz-Jentoft, A. J. [Inappropriate prescription in older patients: the STOPP/START criteria] 2009 Rev Esp Geriatr Gerontol 44 5 273-9 10.1016/j.regg.2009.03.017 19. Drenth-van Maanen, A. C.; Leendertse, A. J.; Jansen, P. A. F.; Knol, W.; Keijsers, Cjpw; Meulendijk, M. C.; van Marum, R. J. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP): Combining implicit and explicit prescribing tools to improve appropriate prescribing 2018 J Eval Clin Pract 24 2 317-22 10.1111/jep.12787 20. Farrell, B.; Tsang, C.; Raman-Wilms, L.; Irving, H.; Conklin, J.; Pottie, K. What are priorities for deprescribing for elderly patients? Capturing the voice of practitioners: a modified delphi process 2015 PLoS One 10 4 e0122246 10.1371/journal.pone.0122246 21. Fick Erratum: Updating the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (Archives of Internal Medicine (December 8) 163:22 (2716-2724)) 2004 Archives of Internal Medicine 164 3 298 10.1001/archinte.164.3.298 22. Fried, T. R.; Niehoff, K.; Tjia, J.; Redeker, N.; Goldstein, M. K. A Delphi process to address medication appropriateness for older persons with multiple chronic conditions 2016 BMC Geriatr 16 67 10.1186/s12877-016-0240-3 23. Gallagher, P.; Ryan, C.; Byrne, S.; Kennedy, J.; O'Mahony, D. STOPP (Screening Tool of Older Person's Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation 2008 Int J Clin Pharmacol Ther 46 2 72-83
24. Gebhart, F. Beers Criteria Update: Catch inappropriate scripts for the elderly 2012 Drug Topics 156 8
25. Gensthaler, B. M. Potentially inappropriate medication list: Unsuitable drugs for seniors 2010 Pharmazeutische Zeitung 155 11
26. Griebling, T. L. Re: American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults 2012 J Urol 188 4 1211-2 10.1016/j.juro.2012.06.105 27. Griebling, T. L. Re: How to Use the American Geriatrics Society 2015 Beers Criteria-A Guide for Patients, Clinicians, Health Systems, and Payors 2016 J Urol 195 3 668 10.1016/j.juro.2015.12.057 28. Griebling, T. L. Re: American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults 2016 J Urol 195 3 667-8 10.1016/j.juro.2015.12.056 29. Groth-Tonberge, C.; Strehl, E. Recommendations of the Priscus List: Potentially inappropriate medications for the elderly 2011 PZ Prisma 18 3 171-82
30. Hannou, S.; Rousseau, A.; Rybarczyk-Vigouret, M. C.; Michel, B. Medication in nursing homes in Alsace: a preferential list of drugs obtained by consensus 2014 Springerplus 3 413 10.1186/2193-1801-3-413 31. Jardin, M.; Bocquier, A.; Cortaredona, S.; Nauleau, S.; Millon, C.; Savard-Chambard, S.; Allaria- Lapierre, V.; Sciortino, V.; Bouvenot, G.; Verger, P. [Potentially inappropriate prescriptions for the elderly: a study of health insurance reimbursements in Southeastern France] 2012 Rev Epidemiol Sante Publique 60 2 121-30 10.1016/j.respe.2011.10.004 32. Lang, P. O.; Petrovic, M.; Dalleur, O.; Ferahta, N.; Benetos, A.; Boland, B. The exercise in applying STOPP/START.v2 in vulnerable very old patients: Towards patient tailored prescribing 2016 European Geriatric Medicine 7 2 176-9 10.1016/j.eurger.2015.12.013 33. Laroche, M. L.; Charmes, J. P.; Merle, L. Potentially inappropriate medications in the elderly: a French consensus panel list 2007 Eur J Clin Pharmacol 63 8 725-31 10.1007/s00228-007-0324-2 34. Mahony, D. O.; Sullivan, D. O.; Byrne, S.; Connor, M. N. O.; Ryan, C.; Gallagher, P. Corrigendum: STOPP/START criteria for potentially inappropriate prescribing in older people: version 2 2018 Age Ageing 47 3 489 10.1093/ageing/afx178 35. Marcum, Z. A.; Hanlon, J. T. Commentary on the new American Geriatric Society Beers criteria for potentially inappropriate medication use in older adults 2012 Am J Geriatr Pharmacother 10 2 151-9 10.1016/j.amjopharm.2012.03.002 36. Martín Lesende, I. Inappropriate prescribing in the elderly: Clinical tools beyond the simple assessment 2011 Revista Espanola de Geriatria y Gerontologia 46 3 117-8 10.1016/j.regg.2011.01.004 37. Marzi, M. M.; Pires, M.; Quaglia, N. [Criteria for defining consensus achievement in Delphi studies that assess potentially inappropriate medications in the elderly] 2016 Rev Fac Cien Med Univ Nac Cordoba 73 2 90-7
38. Molony, S. L. Beers' criteria for potentially inappropriate medication use in the elderly 2003 J Gerontol Nurs 29 11 6
39. Oborne, C. A.; Batty, G. M.; Maskrey, V.; Swift, C. G.; Jackson, S. H. Development of prescribing indicators for elderly medical inpatients 1997 Br J Clin Pharmacol
43 1 91-7
40. Pastor Cano, J.; Aranda Garcia, A.; Gascon Canovas, J. J.; Rausell Rausell, V. J.; Tobaruela Soto, M. [Beers versus STOPP criteria and the possible implications of the Beers criteria's Spanish adaptation] 2017 Farm Hosp 41 n01 130-1 10.7399/fh.2017.41.1.10568 41. Pattanaworasate, W.; Emmerton, L.; Pulver, L.; Winckel, K. Comparison of prescribing criteria in hospitalised Australian elderly 2010 Pharm Pract (Granada) 8 2 132-8
42. Resnick, B.; Pacala, J. T. 2012 Beers Criteria 2012 J Am Geriatr Soc 60 4 612-3 10.1111/j.1532-5415.2012.03921.x 43. Riu Subirana, S.; Martínez Adell, M. N.; Baena Díez, J. Drugs that can change the cognitive state of the elderly 2009 FMC Formacion Medica Continuada en Atencion Primaria 16 5 287-93 10.1016/S1134-2072(09)71279-4 44. Samsa, G. P.; Hanlon, J. T.; Schmader, K. E.; Weinberger, M.; Clipp, E. C.; Uttech, K. M.; Lewis, I. K.; Landsman, P. B.; Cohen, H. J. A summated score for the medication appropriateness index: development and assessment of clinimetric properties including content validity 1994 J Clin Epidemiol 47 8 891-6
45. Schnipper, J. L. Medication safety: are we there yet?: Comment on "Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients" 2011 Arch Intern Med 171 11 1019-20 10.1001/archinternmed.2011.220 46. Singh, J. Evaluation of the appropriateness of prescribing in geriatric patients using Beers' criteria and Phadke's criteria and comparison thereof by Rima Shah and colleagues 2012 J Pharmacol Pharmacother 3 1 81-2 10.4103/0976-500x.92509 47. Stefanacci, R. G.; Cavallaro, E.; Beers, M. H.; Fick, D. M. Developing explicit positive beers criteria for preferred central nervous system medications in older adults 2009 Consult Pharm 24 8 601-10 48. Swagerty, D.; Brickley, R. American Medical Directors Association and American Society of Consultant Pharmacists joint position statement on the Beers List of Potentially Inappropriate Medications in Older Adults 2005 J Am Med Dir Assoc 6 1 80-6 10.1016/j.jamda.2004.12.019 49. Topinková, E.; Fialová, D.; Matějovská Kubešová, H. Potentially inappropriate (risky) drugs at geriatric patients Expert consensus for the Czech Republic 2012 2012 Prakticky Lekar 92 1 11-22 10.1186/1471-2318-4-9 50. Van Den Houdt, F. Plea for deprescribing guideline for elderly patient: 'Deleting in medication list of elderly patient should always be in consultation' 2016 Pharmaceutisch Weekblad 151 21 10-2
51. Zagaria, M. A. E. Ppis: Considerations and resources for deprescribing in older adults 2016 U.S. Pharmacist 41 12 7-10
Not obtained 52. Gundermann, C.; Hartmann, M. Drug interactions in the elderly - the PRISCUS list 2011 Verdauungskrankheiten 29 6 290-7 10.5414/VDX00699
53. Kolzsch, M.; Bolbrinker, J.; Huber, M.; Kreutz, R. [Potentially inappropriate medication for the elderly: adaptation and evaluation of a French consensus list] 2010 Med Monatsschr Pharm 33 8 295-302 Excluded because do not included respiratory disease 1. McLeod, P. J.; Huang, A. R.; Tamblyn, R. M.; Gayton, D. C. Defining inappropriate practices in prescribing for elderly people: a national consensus panel 1997 Cmaj 156 3 385-91 2. Zhan, C.; Sangl, J.; Bierman, A. S.; Miller, M. R.; Friedman, B.; Wickizer, S. W.; Meyer, G. S. Potentially inappropriate medication use in the community-dwelling elderly: findings from the 1996 Medical Expenditure Panel Survey 2001 Jama 286 22 2823-9 3. Grant, R. L.; Batty, G. M.; Aggarwal, R.; Lowe, D.; Potter, J. M.; Pearson, M. G.; Oborne, A.; Jackson, S. H. National sentinel clinical audit of evidence-based prescribing for older people: methodology and development 2002 J Eval Clin Pract 8 2 189-98 4. Daniel C Malone , Jacob Abarca, Philip D Hansten, Amy J Grizzle, Edward P Armstrong, Robin C Van Bergen, Babette S Duncan-Edgar, Steven L Solomon, Richard B Lipton Identification of serious drug-drug interactions: results of the partnership to prevent drug-drug interactions. 2003 J Am Pharm Assoc 10.1331/154434504773062591. 5. Rancourt, C.; Moisan, J.; Baillargeon, L.; Verreault, R.; Laurin, D.; Grégoire, J. P. Potentially inappropriate prescriptions for older patients in long-term care 2004 BMC Geriatrics 4 10.1186/1471-2318-4-9 6. Christian, J. B.; VanHaaren, A.; Cameron, K. A.; Lapane, K. L. Alternatives for potentially inappropriate medications in the elderly population: Treatment algorithms for use in the Fleetwood Phase III study 2004 Consultant Pharmacist 19 11 1011-28 10.4140/TCP.n.2004.1011 7. Catherine I Lindblad , Joseph T Hanlon , Cynthia R Gross , Richard J Sloane , Carl F Pieper , Emily R Hajjar , Christine M Ruby , Kenneth E Schmader Clinically important drug-disease interactions and their prevalence in older adults. 2006 Clin Ther 10.1016/j.clinthera.2006.08.006. 8. Basger, B. J.; Chen, T. F.; Moles, R. J. Inappropriate medication use and prescribing indicators in elderly Australians: development of a prescribing indicators tool 2008 Drugs Aging 25 9 777-93 9. Holmes, H. M.; Sachs, G. A.; Shega, J. W.; Hougham, G. W.; Cox Hayley, D.; Dale, W. Integrating palliative medicine into the care of persons with advanced dementia: identifying appropriate medication use 2008 J Am Geriatr Soc 56 7 1306-11 10.1111/j.1532- 5415.2008.01741.x 10. Soares, M. A.; Fernandez-Llimos, F.; Lanca, C.; Cabrita, J.; Morais, J. A. [Operationalization to Portugal: Beers criteria of inappropriate medication use in the elderly] 2008 Acta Med Port 21 5 441-52 11. Rognstad, S.; Brekke, M.; Fetveit, A.; Spigset, O.; Wyller, T. B.; Straand, J. The Norwegian General Practice (NORGEP) criteria for assessing potentially inappropriate prescriptions to elderly patients. A modified Delphi study 2009 Scand J Prim Health Care 27 3 153-9 10.1080/02813430902992215 12. Rognstad, Sture ;Brekke, Mette ;Gjelstad, Svein ;Straand, Jørund ;Fetveit, Arne Potentially Inappropriate Prescribing to Older Patients: Criteria, Prevalence and an Intervention to Reduce It: The Prescription Peer Academic Detailing (Rx-PAD) Study - A Cluster- Randomized, Educational Intervention in Norwegian General Practice 2018 Basic & clinical pharmacology & toxicology 123 4 380-91 10.1111/bcpt.13040 13. Laroche, M. L.; Bouthier, F.; Merle, L.; Charmes, J. P. [Potentially inappropriate medications in the elderly: a list adapted to French medical practice] 2009 Rev Med Interne 30 7 592-601 10.1016/j.revmed.2008.08.010
14. Holt, S.; Schmiedl, S.; Thurmann, P. A. Potentially inappropriate medications in the elderly: the PRISCUS list 2010 Dtsch Arztebl Int 107 31-32 543-51 10.3238/arztebl.2010.0543 15. Maio, V.; Del Canale, S.; Abouzaid, S. Using explicit criteria to evaluate the quality of prescribing in elderly Italian outpatients: a cohort study 2010 J Clin Pharm Ther 35 2 219-29 10.1111/j.1365-2710.2009.01094.x 16. Galan Retamal, C.; Garrido Fernandez, R.; Fernandez Espinola, S.; Ruiz Serrato, A.; Garcia Ordonez, M. A.; Padilla Marin, V. [Prevalence of potentially inappropriate medication in hospitalized elderly patients by using explicit criteria] 2014 Farm Hosp 38 4 305-16 10.7399/fh.2014.38.4.1148 17. Bermingham, M.; Ryder, M.; Travers, B.; Edwards, N.; Lalor, L.; Kelly, D.; Gallagher, J.; O'Hanlon, R.; McDonald, K.; Ledwidge, M. The St Vincent's potentially inappropriate medicines study: development of a disease-specific consensus list and its evaluation in ambulatory heart failure care 2014 Eur J Heart Fail 16 8 915-22 10.1002/ejhf.132 18. Kuhn-Thiel, A. M.; Weiss, C.; Wehling, M. Consensus validation of the FORTA (Fit fOR The Aged) List: a clinical tool for increasing the appropriateness of pharmacotherapy in the elderly 2014 Drugs Aging 31 2 131-40 10.1007/s40266-013-0146- 0 19. Farhad Pazan , Christel Weiss , Martin Wehling The EURO-FORTA (Fit fOR The Aged) List: International Consensus Validation of a Clinical Tool for Improved Drug Treatment in Older People 2018 Drugs Aging 10.1007/s40266-017-0514-2 20. Lindsay, J.; Dooley, M.; Martin, J.; Fay, M.; Kearney, A.; Khatun, M.; Barras, M. The development and evaluation of an oncological palliative care deprescribing guideline: the 'OncPal deprescribing guideline' 2015 Support Care Cancer 23 1 71-8 10.1007/s00520-014-2322-0 21. Kim, S. O.; Jang, S.; Kim, C. M.; Kim, Y. R.; Sohn, H. S. Consensus Validated List of Potentially Inappropriate Medication for the Elderly and Their Prevalence in South Korea 2015 International Journal of Gerontology 9 3 136-41 10.1016/j.ijge.2015.05.013 22. Nyborg, G.; Straand, J.; Klovning, A.; Brekke, M. The Norwegian General Practice-- Nursing Home criteria (NORGEP-NH) for potentially inappropriate medication use: A web-based Delphi study 2015 Scand J Prim Health Care 33 2 134-41 10.3109/02813432.2015.1041833 23. Pastor Cano, J.; Aranda Garcia, A.; Gascon Canovas, J. J.; Rausell Rausell, V. J.; Tobaruela Soto, M. [Spanish adaptation of Beers criteria] 2015 An Sist Sanit Navar 38 3 375-85 24. Joseph T Hanlon, Todd P Semla, Kenneth E Schmader Alternative Medications for Medications in the Use of High-Risk Medications in the Elderly and Potentially Harmful Drug-Disease Interactions in the Elderly Quality Measures 2015 J Am Geriatr Soc 10.1111/jgs.13807 25. Khodyakov, D.; Ochoa, A.; Olivieri-Mui, B. L.; Bouwmeester, C.; Zarowitz, B. J.; Patel, M.; Ching, D.; Briesacher, B. Screening Tool of Older Person's Prescriptions/Screening Tools to Alert Doctors to Right Treatment Medication Criteria Modified for U.S. Nursing Home Setting 2017 J Am Geriatr Soc 65 3 586-91 10.1111/jgs.14689 26. Lavan, A. H.; Gallagher, P.; Parsons, C.; O'Mahony, D. STOPPFrail (Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy): consensus validation 2017 Age Ageing 46 4 600-7 10.1093/ageing/afx005 27. Faizan Mazhar, Shahzad Akram, Saima Mahmood Malhi, Nafis Haider A prevalence study of potentially inappropriate medications use in hospitalized Pakistani elderly 2017 Aging Clinical and Experimental Research 10.1007/s40520-017-0742-7 28. Morin, L.; Laroche, M. L.; Vetrano, D. L.; Fastbom, J.; Johnell, K. Adequate, questionable, and inadequate drug prescribing for older adults at the end of life: a European expert consensus
2018 Eur J Clin Pharmacol 10.1007/s00228-018-2507- 4 29. By the American Geriatrics Society Beers Criteria® Update Expert, Panel American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults 2019 Journal of the American Geriatrics Society 67 4 674-94 10.1111/jgs.15767 30. Wang, Ke ;Shen, Jianghua ;Jiang, Dechun ;Xing, Xiaoxuan ;Zhan, Siyan ;Yan, Suying Development of a list of high-risk perioperative medications for the elderly: a Delphi method 2019 Expert opinion on drug safety 18 9 853-9 10.1080/14740338.2019.1629416 31. Pazan, Farhad ;Gercke, Yana ;Weiss, Christel ;Wehling, Martin ;Forta Raters The U.S.- FORTA (Fit fOR The Aged) List: Consensus Validation of a Clinical Tool to Improve Drug Therapy in Older Adults 2019 Journal of the American Medical Directors Association S1525- 8610(19)30583-3 10.1016/j.jamda.2019.07.023 32. Motter, Fabiane Raquel ;Hilmer, Sarah Nicole ;Paniz, Vera Maria Vieira Pain and Inflammation Management in Older Adults: A Brazilian Consensus of Potentially Inappropriate Medication and Their Alternative Therapies 2019 Frontiers in pharmacology 10 1408- 10.3389/fphar.2019.01408 33. Wazzan, A. A. A.; Tommelein, E.; Foubert, K.; Bonassi, S.; Onder, G.; Somers, A.; Petrovic, M.; Boussery, K. Development and Application of the GheOP(3)S-Tool Addendum on Potentially Inappropriate Prescribing (PIP) of Renally Excreted Active Drugs (READs) in Older Adults with Polypharmacy 2018 Drugs Aging 35 4 343-64 10.1007/s40266-018-0530- x 34. João Pedro Aguiar , Ana Mafalda Brito , Ana Paula Martins, Hubert G M Leufkens , Filipa Alves da Costa Potentially inappropriate medications with risk of cardiovascular adverse events in the elderly: A systematic review of tools addressing inappropriate prescribing 2019 J Clin Pharm Ther doi: 10.1111/jcpt.12811. 35. João Pedro Aguiar , Luís Heitor Costa , Filipa Alves da Costa , Hubert Gm Leufkens , Ana Paula Martins Identification of potentially inappropriate medications with risk of major adverse cardiac and cerebrovascular events among elderly patients in ambulatory setting and cerebrovascular events among elderly patients in ambulatory setting and long-term care facilities 2019 Clin Interv Aging 10.2147/CIA.S192252 Excluded because do not included mental or behavior disorder 1. Zhan, C.; Sangl, J.; Bierman, A. S.; Miller, M. R.; Friedman, B.; Wickizer, S. W.; Meyer, G. S. Potentially inappropriate medication use in the community-dwelling elderly: findings from the 1996 Medical Expenditure Panel Survey 2001 Jama 286 22 2823-9 2. Grant, R. L.; Batty, G. M.; Aggarwal, R.; Lowe, D.; Potter, J. M.; Pearson, M. G.; Oborne, A.; Jackson, S. H. National sentinel clinical audit of evidence-based prescribing for older people: methodology and development 2002 J Eval Clin Pract 8 2 189-98
3. Daniel C Malone , Jacob Abarca, Philip D Hansten, Amy J Grizzle, Edward P Armstrong, Robin C Van Bergen, Babette S Duncan-Edgar, Steven L Solomon, Richard B Lipton Identification of serious drug-drug interactions: results of the partnership to prevent drug-drug interactions. 2003 J Am Pharm Assoc 10.1331/154434504773062591. 4. Rancourt, C.; Moisan, J.; Baillargeon, L.; Verreault, R.; Laurin, D.; Grégoire, J. P. Potentially inappropriate prescriptions for older patients in long-term care 2004 BMC Geriatrics 4 10.1186/1471-2318-4-9 5. Basger, B. J.; Chen, T. F.; Moles, R. J. Inappropriate medication use and prescribing indicators in elderly Australians: development of a prescribing indicators tool 2008 Drugs Aging 25 9 777-93
6. Holmes, H. M.; Sachs, G. A.; Shega, J. W.; Hougham, G. W.; Cox Hayley, D.; Dale, W. Integrating palliative medicine into the care of persons with advanced dementia: identifying appropriate medication use 2008 J Am Geriatr Soc 56 7 1306-11 10.1111/j.1532-5415.2008.01741.x 7. Maio, V.; Del Canale, S.; Abouzaid, S. Using explicit criteria to evaluate the quality of prescribing in elderly Italian outpatients: a cohort study 2010 J Clin Pharm Ther 35 2 219-29 10.1111/j.1365-2710.2009.01094.x 8. Bermingham, M.; Ryder, M.; Travers, B.; Edwards, N.; Lalor, L.; Kelly, D.; Gallagher, J.; O'Hanlon, R.; McDonald, K.; Ledwidge, M. The St Vincent's potentially inappropriate medicines study: development of a disease-specific consensus list and its evaluation in ambulatory heart failure care 2014 Eur J Heart Fail 16 8 915-22 10.1002/ejhf.132 9. Kuhn-Thiel, A. M.; Weiss, C.; Wehling, M. Consensus validation of the FORTA (Fit fOR The Aged) List: a clinical tool for increasing the appropriateness of pharmacotherapy in the elderly 2014 Drugs Aging 31 2 131-40 10.1007/s40266-013-0146- 0 10. Farhad Pazan , Christel Weiss , Martin Wehling The EURO-FORTA (Fit fOR The Aged) List: International Consensus Validation of a Clinical Tool for Improved Drug Treatment in Older People 2018 Drugs Aging 10.1007/s40266-017-0514-2 11. Lindsay, J.; Dooley, M.; Martin, J.; Fay, M.; Kearney, A.; Khatun, M.; Barras, M. The development and evaluation of an oncological palliative care deprescribing guideline: the 'OncPal deprescribing guideline' 2015 Support Care Cancer 23 1 71-8 10.1007/s00520-014-2322-0 12. Pastor Cano, J.; Aranda Garcia, A.; Gascon Canovas, J. J.; Rausell Rausell, V. J.; Tobaruela Soto, M. [Spanish adaptation of Beers criteria] 2015 An Sist Sanit Navar 38 3 375-85 13. Morin, L.; Laroche, M. L.; Vetrano, D. L.; Fastbom, J.; Johnell, K. Adequate, questionable, and inadequate drug prescribing for older adults at the end of life: a European expert consensus 2018 Eur J Clin Pharmacol 10.1007/s00228-018-2507- 4 14. Pazan, Farhad ;Gercke, Yana ;Weiss, Christel ;Wehling, Martin ;Forta Raters The U.S.- FORTA (Fit fOR The Aged) List: Consensus Validation of a Clinical Tool to Improve Drug Therapy in Older Adults 2019 Journal of the American Medical Directors Association S1525- 8610(19)30583-3 10.1016/j.jamda.2019.07.023 15. João Pedro Aguiar , Ana Mafalda Brito , Ana Paula Martins, Hubert G M Leufkens , Filipa Alves da Costa Potentially inappropriate medications with risk of cardiovascular adverse events in the elderly: A systematic review of tools addressing inappropriate prescribing 2019 J Clin Pharm Ther doi: 10.1111/jcpt.12811. 16. João Pedro Aguiar , Luís Heitor Costa , Filipa Alves da Costa , Hubert Gm Leufkens , Ana Paula Martins Identification of potentially inappropriate medications with risk of major adverse cardiac and cerebrovascular events among elderly patients in ambulatory setting and cerebrovascular events among elderly patients in ambulatory setting and long-term care facilities 2019 Clin Interv Aging 10.2147/CIA.S192252 17. Wazzan, A. A. A.; Tommelein, E.; Foubert, K.; Bonassi, S.; Onder, G.; Somers, A.; Petrovic, M.; Boussery, K. Development and Application of the GheOP(3)S-Tool Addendum on Potentially Inappropriate Prescribing (PIP) of Renally Excreted Active Drugs (READs) in Older Adults with Polypharmacy 2018 Drugs Aging 35 4 343-64 10.1007/s40266-018-0530- x
Table 3. Commercialization and essentiality of potentially inappropriate medications for elderly. Essential by Essential by World National List of Drugs Marketed in Brazil Health Essential Medicines Organization - Brazil Acarbose 1 0 0 Aceclofenac 1 0 0 Acemetacin 0 0 0 Acenocumarol 0 0 0 Acepromethazine 0 0 0 Acetazolamide 1 1 1 Acetylsalicylic acid 1 1 1 Acipimox 0 0 0 Adrenaline 1 1 1 Alclofenac 0 0 0 Alendronate 1 1 0 Alimemazine 0 0 0 Alizapride 1 0 0 Allopurinol 1 1 1 Aloe vera 1 1 0 Alprazolam 1 0 0 Alteplase 1 1 1 Aluminum hydroxide 1 1 0 Amantadine 1 1 0 Aminophylline 1 0 0 Amiodarone 1 1 1 Amisulpride 1 0 0 Amitriptyline 1 1 1 Amobarbital 1 0 0 Amoxapine 1 0 0 Aniracetam 0 0 0 Apixaban 1 0 0 Aripiprazole 1 0 0 Aripiprazole 1 0 0 Atenolol 1 1 1 Atropina 1 1 1 Azapropazone 0 0 0 Azatadine 1 0 0 Azathioprine 1 1 1 Baclofen 1 0 0 Belladonna 1 0 0 Bentazepam 0 0 0 Benzatropine 0 0 0 Benzidamine 1 0 0 Benzocaine 1 0 0 Betamethasone 1 1 1 Bevacizumab 1 0 1 Bezafibrat 1 1 0 Bifemelane 0 0 0 Biperiden 1 1 1 Bisacodyl 1 0 0 Bisoprolol 1 0 1 Bornaprine 0 0 0 Bromazepam 1 0 0 Bromocriptine 1 1 0 Bronfeniramine 1 0 0
Brotizolam 1 0 0 Buclizine 1 0 0 Buflomedil 1 0 0 Buformin 1 0 0 Bumetanide 1 0 0 Buprenorphine 1 0 0 Butabarbital 1 0 0 Butalbital 1 0 0 Butorphanol 1 0 0 Butylscopolamine 1 0 0 Cabergoline 1 1 0 Calcium 1 1 1 Captopril 1 1 0 Carbamazepine 1 1 1 Carbimazole 0 0 0 Carbinoxamine 1 0 0 Carbutamide 0 0 0 Carisoprodol 1 0 0 Carteolol 0 0 0 Cáscara-sagrada (rhamnus 1 1 0 purshiana dc.) Castor oil 1 0 0 Celecoxibe 1 0 0 Cetazolam 1 0 0 Chloral hydrate 0 0 0 Chlorocyclizine 0 0 0 Chlorodiazepoxide 1 0 0 Chlorodiazepoxide + 0 0 0 amitriptyline Chlorodiazepoxide + 0 0 0 clidinium bromide Chlorpheniramine 1 0 0 Chlorpromazine 1 1 1 Chlorpropamide 1 0 0 Chlorprothixene 0 0 0 Chlorzoxazone 1 0 0 Cholestyramine 1 0 0 Ciamemazine 1 0 0 Cilostazol 1 0 0 Cimetidine 1 0 0 Cinnarizine 1 0 0 Citicoline 1 0 0 Clarithromycin 1 1 0 Clemastine 1 0 0 Clidinium 0 0 0 Clobazam 1 1 0 Clobazepam 0 0 0 Clomethazole 0 0 0 Clomipramine 1 1 1 Clonazepam 1 1 0 Clonidine 1 0 0 Clonixin 0 0 0 Clopidogrel 1 1 1 Clorazepate 1 0 0 Clothiapine 0 0 0 Clotiazepam 1 0 0 Cloxazolam 0 0 0 Clozapine 1 1 1
Codeine 1 1 1 Codergocrine 1 0 0 Colchicine 1 0 0 Colestipol 1 0 0 Conbercept 0 0 0 Cyclandelate 0 0 0 Cyclizine 0 0 1 Cyclobenzaprine 1 0 0 Cyproheptadine 1 0 0 Dabigatran 1 0 1 Dantrolene 1 0 0 Deflazacort 1 0 0 Denosumab 1 0 0 Desipramine 1 0 0 Desmopressin 1 1 1 Dexamethasone 1 1 1 Dexbromopheniramine 1 0 0 Dexchlorpheniramine 1 1 0 Dexchlorpheniramine + 0 0 0 betamethasone Dexibuprofen 0 0 0 Dexketoprofen 0 0 0 Dexmedetomidine 1 0 0 Dextroamphetamine 0 0 0 Dextromethorphan 1 0 0 Dextropropoxyphene 0 0 0 Diazepam 1 1 1 Diclofenac 1 0 0 Dicyclomine 1 0 0 Dicycloverine 1 0 0 Diflunisal 1 0 0 Digitoxin 1 0 0 Digoxin 1 1 1 Dihexazine 0 0 0 Dihexverine 0 0 0 Dihydroergocriptine 0 0 0 Dihydroergocristine 1 0 0 Dihydroergocristine mesylate 0 0 0 + raubasin Dihydroergotoxin 0 0 0 Diltiazem 1 0 0 Dimenhydrinate 1 0 0 Dimethindene 1 0 0 Dioctyl sodium sulfosuccinate 1 0 0 Diphenhydramine 1 0 0 Diphenoxylate 1 0 0 Diphenoxylate + atropine 1 0 0 Diphenylpyralin 0 0 0 Dipyridamole 1 0 0 Disopyramide 1 0 0 Dolantina 1 0 0 Domperidone 1 0 0 Donepezil 1 1 0 Dosulepin 1 0 0 Doxazosin 1 1 0 Doxepin 1 0 0 Doxylamine 1 0 0 Dronedarone 1 0 0
Duloxetine 1 0 0 Enoxaparin sodium 1 1 1 Eplerenone 0 0 0 Ergoline 1 1 0 Erythropoietin 1 0 0 Escin 1 0 0 Escitalopram 1 0 0 Estazolam 1 0 0 Estradiol 1 1 0 Estriol 1 1 0 Estrogen + 1 0 0 hydroxyprogesterone Estrogen + 1 0 1 medroxyprogesterone Estrogen + norethindrone 1 0 1 Estrogen + norgestrel 1 1 0 Estrogens + progesterone 1 0 0 Eszopiclone 1 0 0 Etanercept 1 0 0 Ethacrylic acid 0 0 0 Ethyl loflazepate 1 0 0 Etizolam 0 0 0 Etodolac 1 0 0 Etomidate 0 0 0 Etoricoxib 1 0 0 Ezetimibe 1 0 0 Famotidine 1 0 0 Fentanyl 1 0 1 Fentiazac 0 0 0 Fesoterodine 0 0 0 Finasteride 1 1 0 Flavoxate 0 0 0 Flecainide 0 0 0 Fludiazepam 1 0 0 Fludrocortisone 1 1 1 Flufenamic acid 1 0 0 Flunarizine 1 0 0 Flunitrazepam 1 0 0 Fluocortolone 1 0 0 Fluoxetine 1 1 1 Flupentixol 0 0 0 Fluphenazine 0 0 1 Flurazepam 1 0 0 Flurbiprofen 1 0 0 Fluvoxamine 1 0 0 Folic acid 1 1 1 Fondaparinux sodium 1 0 0 Furosemide 1 1 1 Gabapentin 1 1 0 Ginkgo biloba 1 0 0 Glibenclamide 1 1 0 Glimepiride 1 0 0 Glipizide 1 0 0 Glycopyrronium 1 0 0 Guanabenz 0 0 0 Guanadrel 0 0 0 Guanetidine 0 0 0 Guanfacin 1 0 0
Halazepam 1 0 0 Haloperidol 1 1 1 Haloxazolam 0 0 0 Homatropin methylbromide 1 0 0 Homochlorcyclizine 0 0 0 Huperzine A 0 0 0 Hydralazine 1 1 1 Hydrochlorothiazide 1 1 1 Hydrocortisone 1 1 1 Hydroquinidine 0 0 0 Hydrosmin 1 0 0 Hydroxyzine 1 0 0 Hyoscyamine 1 0 0 Ibuprofen 1 1 1 Imidafenacin 0 0 0 Imipramine 1 0 0 Indomethacin 1 0 0 Insulin 1 1 1 Ipratropium bromide 1 1 1 Iron 1 1 1 Isonixin 0 0 0 Isosorbide dinitrate 1 1 1 Isosorbide mononitrate 1 1 0 Isoxsuprine 1 0 0 Itraconazole 1 1 1 Ivabradine 1 0 0 Ketoprofen 1 0 0 Ketotifen 1 0 0 Leflunomide 1 1 0 Levodopa 1 1 0 Levodopa + benserazide 1 1 0 Levomepromazine 1 0 0 Levothyroxine 1 1 1 Lidocaine 1 1 1 Lithium carbonate 1 1 1 Loperamide 1 0 1 Loprazolam 1 0 0 Lorazepam 1 0 1 Lormetazepam 1 0 0 Lornoxicam 1 0 0 Loxapine 0 0 0 Loxoprofene 1 0 0 Lurasidone 1 0 0 Magnesium 1 1 1 Maprotiline 1 0 0 Meclizine 1 0 0 Meclofenamate 0 0 0 Meclophenamic acid 1 0 0 Medazepam 1 0 0 Mefenamic acid 0 0 0 Megestrol 1 0 0 Melitracene 0 0 0 Meloxicam 1 0 0 Melperone 0 0 0 Memantine 1 1 0 Meperidine 1 0 0 Meprobamate 1 0 0 Mepyramine 1 0 0
Mequitazine 0 0 0 Mesoridazine 1 0 0 Metamizole (dipyrone) 1 1 0 Metaxalone 0 0 0 Metformin 1 1 1 Methotrexate 1 1 1 Methyldigoxin 0 0 0 Methyldopa 1 1 1 Methyldopa + 1 0 0 hydrochlorothiazide Methylphenidate 1 0 0 Methylphenobarbital 1 0 0 Methylprednisolone 1 1 1 Methyltestosterone 1 0 0 Metocarbamol 1 0 0 Metoclopramide 1 1 1 Metolazone 0 0 0 Metopimazine 0 0 0 Metoprolol 1 1 0 Mexazolam 0 0 0 Midazolam 1 1 1 Miglitol 0 0 0 Mineral oil 1 1 0 Minoxidil 1 0 0 Mirtazapine 1 0 0 Montelukast 1 0 0 Morphine 1 1 1 Moxonidine 0 0 0 Nabumetone 0 0 0 Naftidrofuril 0 0 0 Nalbufin 1 0 0 Naproxen 1 1 0 Nateglinide 1 0 0 Niacin 1 1 0 Nicardipine 1 1 0 Nicergolin 1 0 0 Nicotinic acid 1 1 0 Nifedipine 1 1 1 Niflumic acid 0 0 0 Nimesulide 1 0 0 Nimodipine 1 0 0 Nitrazepam 1 0 0 Nitrofurantoin 1 1 0 Nizatidine 1 0 0 Nordazepam 1 0 0 Nortriptyline 1 1 0 Ofloxacin 1 1 1 Olanzapine 1 1 0 Orphenadrine 1 0 0 Oxaprozine 0 0 0 Oxatomide 0 0 0 Oxazepam 1 0 0 Oxazolam 0 0 0 Oxcarbazepine 1 0 0 Oxomemazine 1 0 0 Oxybutynin 1 0 0 Oxymetazoline 1 0 0 Paliperidone 1 0 0
Parecoxib 1 0 0 Paroxetine 1 0 0 Penfluridol 1 0 0 Pentazocine 1 0 0 Pentobarbital 1 0 0 Pentoxifylline 1 1 0 Perfenazine 1 0 0 Pergolide 0 0 0 Periciazine 1 1 0 Perospirone 0 0 0 Perphenazine + amitriptyline 1 0 0 Phenindamine 0 0 0 Pheniramine 1 0 0 Phenobarbital 1 1 1 Phenolphthalein 0 0 0 Phenoprofen 1 0 0 Phenylbutazone 1 0 0 Phenylephrine 1 0 0 Phenytoin 1 1 1 Picetoprofen 0 0 0 Pimetixene 1 0 0 Pimozide 1 0 0 Pinaverium 1 0 0 Pinazepam 0 0 0 Pioglitazone 1 0 0 Pipamperone 0 0 0 Pipothiazine 1 0 0 Piracetam 1 0 0 Piribedil 1 0 0 Piroxicam 1 0 0 Potassium 1 1 1 Pramipexole 1 1 0 Prasugrel 1 0 0 Prazepam 1 0 0 Prazosin 1 0 0 Prednisolone 1 1 0 Prednisone 1 1 0 Pregabalin 1 0 0 Prochlorperazine 0 0 0 Procyclidine 0 0 0 Proglumetacin 0 0 0 Promazine 1 0 0 Promethazine 1 1 0 Propafenone 1 1 0 Propanolol 1 1 0 Propantheline 0 0 0 Propinoxate 1 0 0 Propiomazine 0 0 0 Propiverine 0 0 0 Propofol 1 0 1 Propoxyphene 1 0 0 Protipendil 0 0 0 Protriptyline 0 0 0 Pseudoephedrine 1 0 0 Pyridoxine 1 1 0 Quazepam 0 0 0 Quetiapine 1 1 0 Quinidine 1 0 0
Ranibizumab 1 0 0 Ranitidine 1 1 1 Ranolazine 1 0 0 Reboxetine 1 0 0 Repaglinide 1 0 0 Reserpina 1 0 0 Reserpine + 0 0 0 hydrochlorothiazide Rilmenidine 1 0 0 Risperidone 1 1 1 Rituximab 1 1 1 Rivaroxaban 1 0 0 Rivastigmine 1 1 0 Ropinirole 0 0 0 Rotigotine 1 0 0 Sacubitril + valsartan 1 0 0 Scopolamine 1 0 0 Secobarbital 1 0 0 Selegiline 1 1 0 Senna alexandrina 1 0 1 Sertindol 0 0 0 Sertraline 1 0 0 Sildenafil 1 1 0 Sitagliptin 1 0 0 Sodium heparin 1 1 1 Sodium picosulfate 1 0 0 Sodium warfarin 1 1 0 Solifenacin 1 0 0 Somatropin 1 1 0 Sotalol 1 0 0 Spironolactone 1 1 1 Strontium ranelate 1 0 0 Stropipate 0 0 0 Sucralfate 1 0 0 Sulfamethoxazole 1 1 1 Sulindac 0 0 0 Sulpiride 1 0 0 Suvorexanto 0 0 0 Tadalafila 1 0 0 Tamsulosin 1 0 0 Temazepam 1 0 0 Tenoxicam 1 0 0 Terazosin 1 0 0 Teriparatide 1 0 0 Testosterone 1 0 1 Tetrazepam 1 0 0 Theophylline 1 0 0 Thiaprofenic acid 0 0 0 Thiethylperazine 0 0 0 Thiocolchicoside 1 0 0 Thiopental 1 0 0 Thioridazine 1 0 0 Thymoxamine 0 0 0 Tiapride 0 0 0 Ticagrelor 1 0 0 Ticlopidine 1 0 0 Tiemonium 0 0 0 Tirepramide 0 0 0
Tizanidine 1 0 0 Tolmetine 0 0 0 Tolterodine 0 0 0 Topiramate 1 1 0 Torasemide 0 0 0 Tramadol 1 0 0 Tranylcypromine 1 0 0 Trazodone 1 0 0 Trianterene 0 0 0 Triazolam 1 0 0 Triexiphenidyl 1 1 0 Trifluoperazine 0 0 0 Trimetazidine 1 0 0 Trimethoprim 1 1 1 Trimetobenzamide 1 0 0 Trimipramine 1 0 0 Tripelenamine 1 0 0 Triprolidine 1 0 0 Tromethamine ketorolac 1 0 0 Tropatepine 0 0 0 Tropio 0 0 0 Troxerrutin + vincamine 0 0 0 Urapidil 0 0 0 Valproic acid (sodium 1 1 1 valproate) Vancomycin 1 0 1 Venlafaxine 1 0 0 Verapamil 1 1 0 Vinburnine 0 0 0 Vincamine 0 0 0 Vincamine-rutine 0 0 0 Vincristine 1 0 1 Voglibose 0 0 0 Zafirlukast 1 0 0 Zaleplom 1 0 0 Ziprasidone 1 1 0 Zolpidem 1 0 0 Zoplicone 1 0 0 Zotepina 0 0 0 Zuclopentixol 0 0 0 Total 366 118 51
Table 4. Ten potentially inappropriate medication with a higher number of citations by tools, in decreasing order of citations. Potentially inappropriate Reason/risks and adverse drugs events Therapeutic Management medication (n) Digoxin (30) • Considered inappropriate medication in doses greater than 0.125 • For tachycardia or atrial fibrillation: beta-blockers; mg/day; • Congestive heart failure: heart failure diuretics, angiotensin • Risk of toxicity due to decreased renal clearance and abnormal converting enzyme inhibitors; serum potassium; • Amiodarone and digitoxin may be less toxic; • Overdose in renal failure causing nausea, vomiting, drowsiness, • Monitoring of cardiovascular and renal function, concentration visual disturbances and disturbances in heart rhythm (arrhythmias of digoxin and potassium and adverse drug reactions; and heart block); • Dose reduction; • Mortality in the elderly with atrial fibrillation or heart failure. • Can be used to control heart failure with atrial fibrillation and to treat acute heart failure for a short period. Amitriptyline (26) • Peripheral anticholinergic effects (constipation, dry mouth, • Citalopram 20 mg; orthostatic hypotension, cardiac arrhythmia) and central effects • Bupropion 150 mg; (drowsiness, internal restlessness, confusion, delirium); • Mirtazapine 15-30 mg; • Cardiac effects; • Sertraline 75-100 mg; • Muscarinic block; • Paroxetine 20-30mg; • Sedation; • Venlafaxine up to 150 mg; • Cognitive impairment; • Desipramine dose up to 75 mg; • Orthostatic hypotension; • Nortriptyline 10-25 mg; • Dizziness; • For insomnia: trazodone 75-150 mg in 3 divided doses. • Falls and fractures; • For depression: serotonin and norepinephrine reuptake • Prolongation of the QT interval; inhibitors, selective serotonin reuptake inhibitors and • Ventricular arrhythmia; buproprione; • Sudden cardiac death. • For neuropathic pain: gabapentin, topical capsaicin, pregabalin, lidocaine patch; • Non-pharmacological treatments. Diazepam (25) • Prolonged sedation; • Withdrawal; • Falls and fractures; • Benzodiazepines (short or intermediate half-life); • Retrograde amnesia; • Zopiclone, in low dose; • Suppressive effects of the central nervous system; • Opipramol; • Cognitive impairment; • Sedative antidepressants (e.g. mirtazapine); • Dependence; • Low-power neuroleptics (e.g., melperone, pipamperon); • Daytime sedation; • Mirtazapine; • Muscle weakness; • Trazodone; • Mianserin;
• Psychiatric drug reactions (agitation, irritability, hallucinations, • Alprazolam (not to exceed doses of 4 mg); psychosis); • Buspirone 20-30 mg (must not exceed doses of 60 mg); • Accumulation in the body, due to prolonged elimination half-life. • Lorazepam 0.5 mg (not to exceed doses of 3 mg); • Oxazepam 10 mg (not to exceed doses of 60 mg); • Zolpidem 5 mg; • Temazepam 7.5 mg, up to 15 mg; • Zaleplom 5 mg (do not exceed 7 to 10 days). • Clinical monitoring of adverse drug reactions (cognitive function, surveillance, regular history of falls, gait firmness test, psychopathology, ataxia); • Non-pharmacological treatment and consider reducing dosage and/or discontinuation. Indomethacin (24) • Neurological adverse drug events (severe headache, dizziness, • Allopurinol vertigo, fogging); • Topical agents (e.g. lidocaine adhesive); • Renal toxicity, especially in patients with pre-existing chronic • COX-2 inhibitors; kidney disease; • Paracetamol; • Fluid retention and fluid overload causing decompensated heart • Metamizole (dipyrone) 500-1000mg; failure in patients with underlying cardiac dysfunction; • Ibuprofen 2400 mg for 24 hours; • Edema; • Naproxen 1000 mg for 24 hours; • Bleeding, • Magnesium trisalicylate choline 5500 mg during 24 hours; • Ulceration or gastrointestinal perforation. • Celecoxib for osteoarthritis 200mg; • Valdecoxib for osteoarthritis and rheumatoid arthritis 10 mg; • Opioids (weak); • Use in combination with protective agents (e.g. proton pump inhibitors); • Monitor of gastrointestinal manifestations (e.g. gastritis, ulcer, hemorrhage), renal function and cardiovascular function (e.g. blood pressure, signs of congestive heart failure); • Non-pharmacological treatment (example, physiotherapy, acupuncture, thermotherapy, electrostimulation, and therapeutic massage). Meperidine • Falls and fractures; • Do not use more than 30 days. (Pethidine) (22) • Confusion; • Morphine of 15 to 30 mg every 4 hours; • Dependence; • Oxycodone 5 to 10 mg for 3 to 4 hours; • Withdrawal; • Fentanyl 25 mcg per hour (not to exceed 300 mcg / hour); • Seizures; • Hydromorphone; • Respiratory depression; • Weak non-steroidal anti-inflammatory (e.g., ibuprofen);
• Gastrointestinal effects; • Buprenorphine adhesive; • Neurotoxicity. • Mitamizole (dipyrone) 500-1000 mg; • Non-pharmacological treatment (for example, physiotherapy, acupuncture, thermotherapy, electrostimulation and therapeutic massage); • Clinical monitoring (central nervous function, tendency to fall, cardiovascular function); • Monitoring of kidney function. Ticlopidine (22) • Toxicity; • Acetylsalicylic acid (50 to 325mg); • Bleeding; • Dipyridamole (200mg); • Bone marrow suppression; • Clopidogrel (75mg); • Potentially fatal hematological adverse reactions • Monitor blood counts. (neutropenia/agranulocytosis, thrombotic thrombocytopenic • If necessary, discontinue treatment 10 to 14 days before surgery. purpura and aplastic anemia); • Severe hepatic effects; • Lack of effectiveness. Chlorpheniramine • Peripheral anticholinergic effects (dry mouth, constipation, • Second-generation antihistamines: loratadine 10 mg; cetirizine (21) hypotension, arrhythmia) and central (confusion, delirium, 10 mg; fexofenadine 60 mg; and intranasal steroid (e.g. dizziness, restlessness); beclomethasone, fluticasone); • Confusion; • For rhinitis: abstain or saline; • Sedation; • For nausea: domperidone; • Cognitive impairment; • For vertigo: betahistine or acetyl-leucine; • Prolongation of the QT interval; • For coughs: non-opioid and non-antihistamines (e.g. clobutinol, • Decreased clearance; olexadine). • Ventricular arrhythmia; • Discontinue treatment one day before surgery. • Sudden cardiac death. Piroxicam (21) • Bleeding from the upper gastrointestinal tract. • Paracetamol; • Gastrointestinal ulceration or perforation; • Codeine; • Renal failure; • Weak opioids (tramadol, codeine); • Arterial hypertension; • COX-2 inhibitors; • Heart failure; • Metamizole (dipyrone) 500-1000 mg; • Fluid retention and fluid overload. • Non-pharmacological treatment (e.g. physical therapy, • Inappropriate at dosages greater than 20 mg per day acupuncture, thermotherapy, electrostimulation and therapeutic massage); • Use in combination with gastric protection agents, for example, proton pump inhibitors;
• Monitoring of gastrointestinal manifestations, renal function and cardiovascular function. Metildopa (19) • Bradycardia; Clonidine at bedtime (not to exceed 2.4 mg per day); • Disturbance of central nervous system function, causing depression • Angiotensin-converting enzyme inhibitors; and sedation, due to a2 agonist effects; risk of affecting the • Angiotensin receptor antagonists; autonomic nervous system, causing orthostatic hypotension; • Thiazide diuretics; • Syncope; • Beta-blockers; • Sedation; • Calcium antagonists - long-acting and with peripheral effect) • Cardiac impairment. • Monitor cardiovascular function. Nifedipina (19) • Hypotension; • Other antihypertensive (e.g. angiotensin converting enzyme • Constipation; inhibitors, angiotensin receptor blockers, thiazide diuretics, • Increased sympathetic response (increased heart rate, contractility, beta-blockers, calcium antagonists, long acting dihydropyridine and cardiac output). (e.g. amlodipine); except centrally acting antihypertensive and • Myocardial infarction; reserpine); • Stroke; • For atrial fibrillation: non-hydropyridine (e.g., diltiazem), beta- • Fluctuations in blood pressure; blocker; • Reflex tachycardia; • For control heart rate: dofetilide, flecainide, propafenone; • Cardiovascular events; • Monitor cardiovascular function and peripheral edema. • Mortality.
Table 5. Ten potentially inappropriate classes of medication with the highest number of citations by tools, in decreasing order. Potentially inappropriate Reason, risks, and adverse drugs events Therapeutic Management pharmacological classes (n) • Breast and endometrial cancer; • The risk/benefit of topical preparations with estrogens • Coronary heart disease; should be assessed. Estrogens (17) • Stroke; • Pulmonary embolism; • Deep vein thrombosis. • Serious adverse reactions; • Paracetamol; • Gastrointestinal ulcers; • Weak Opioids (e.g. codeine); Non-steroidal anti- • Bleeding; • Weak Non-steroidal anti-inflammatories (e.g. ibuprofen); inflammatories (13) • Kidney and liver failure; • COX-2 inhibitors; • Hypertension. • Use proton pump inhibitors; • Non-pharmacological treatment can be used. • Peripheral and central anticholinergic effects; • Selective serotonin reuptake inhibitors; • Sedatives; • Serotonin and norepinephrine reuptake inhibitors. Tricyclic antidepressants (10) • Cognitive impairment; • Cardiotoxicity. • Falls and fractures; • Benzodiazepines (short or intermediate half-life); • Confusion; Benzodiazepines (10) • Dependence; • Abstinence. • Delirium; Not reported • Orthostatic hypotension; Antihistamines (9) • Anticholinergic effects; • Prolongation of the QT interval. • Anticholinergic effects; • Discontinue pharmacological therapy; Antipsychotics (9) • Stroke. • Non-pharmacological therapy. • Inappropriate for more than 8 weeks. • Assess the need for chronic use; Proton pump inhibitors (9) • Discontinue. • Hypotension; • Initiate treatment with smaller doses; Angiotensin-converting • Hyperkalemia; • Monitoring of kidney function closely. enzyme inhibitors (7) • Renal failure. • Prolonged hypoglycemia. • Metformin Sulphonylurea (7) • Other short-acting sulfonylurea. Corticosteroids (6) • Systemic adverse drug reactions. • NR
Table 6. Medication or pharmacological classes with the highest number of interactions. Medication/pharmacological classes – Reason, risks, and adverse drugs events Therapeutic Management medication/pharmacological classes Medication Warfarin Metronidazole • Increase the anticoagulant effect of warfarin NR Pharmacological class: antiarrhythmic (quinidine only) NR NR Pharmacological class: fibrates NR NR Pharmacological class: fibrates (clofibrate only) NR NR Pharmacological class: fluoroquinolones (norfloxacin only) • Bleeding. NR Pharmacological class: macrolides NR NR Pharmacological class: penicillin (amoxicillin, ampicillin • Bleeding. NR only) Pharmacological class: quinolones NR NR Pharmacological class: quinolones (ciprofloxacin, • Bleeding. NR ofloxacin only) Pharmacological class: selective norepinephrine reuptake • Bleeding. NR inhibitors Pharmacological class: selective serotonin reuptake • Bleeding. NR inhibitors Pharmacological class: sulfonamides (sulfamethoxazole NR NR only) Pharmacological class: sulfonamides (trimethoprim + • Bleeding; NR sulfamethoxazole only) • Risk of increase the anticoagulant effects of warfarin, as it inhibits the metabolism of warfarin. Pharmacological class: sulfonamides (trimethoprim only) NR NR Pharmacological class: thyroid hormone (levothyroxine NR NR only) Pharmacological class: triazole antifungals (fluconazole • Bleeding. NR only) Sulfinpyrazone NR NR
Acetylsalicylic acid Pharmacological class: anticoagulants • Upper gastrointestinal ulcer; • Proton pump inhibitors; • Severe bleeding. • H2 histamine receptor antagonist. Pharmacological class: anticoagulants (warfarin only) • Bleeding. • Use gastric protection. Pharmacological class: antidepressants • Upper gastrointestinal ulcer; • Preferable proton pump inhibitors; • Severe bleeding. • H2 histamine receptor antagonist. Pharmacological class: antiplatelet agents • Upper gastrointestinal ulcer; • Preferable proton pump inhibitors; • Severe bleeding. • H2 histamine receptor antagonist. Pharmacological class: antiplatelet agents (only • Without evidence of benefit the association of NR clopidogrel) medications; • Bleeding. Pharmacological class: corticosteroids • Ulcers; • Preferable proton pump inhibitors; • Severe bleeding. • H2 histamine receptor antagonist. Pharmacological class: direct thrombin inhibitors • No evidence of benefit to the association of drugs. NR Pharmacological class: factor Xa inhibitors • No evidence of benefit to the association of drugs. NR Pharmacological class: non-steroidal anti-inflammatory • Coagulation disorders; • Monitoring of international drugs • Potentiate gastrointestinal irritation; standardized ratio; • Peptic ulcer. • Gastric prophylaxis with proton pump inhibitors Pharmacological class: vitamin K antagonists • No evidence of benefit to the association of drugs. NR Digoxin Calcium • If the patient has hypercalcemia, risk of arrhythmia. NR Pharmacological class: antiarrhythmics (propafenone, NR NR quinidine only) Pharmacological class: azalides (azithromycin, • Toxicity. NR clarithromycin, erythromycin only) Pharmacological class: calcium channel blockers NR • Use the lowest dosage of digoxin; (diltiazem, verapamil only) • Monitor serum levels. Pharmacological class: calcium channel blockers • Toxicity. NR (verapamil only) Pharmacological class: loop diuretic • Increase renal potassium and magnesium excretion, NR causing electrolyte imbalance Pharmacological class: statins (atorvastatin only) • Toxicity. NR
Pharmacological class: macrolides • Toxicity. • Use another pharmacological class of antibiotic; • Monitor serum digoxin levels. Pharmacological class: thiazides (hydrochlorothiazide • Increase renal potassium and magnesium excretion, NR only) causing electrolyte imbalance Vitamin D • Increase renal potassium and magnesium excretion, NR causing electrolyte imbalance Cimetidine Pharmacological class: antiarrhythmic drugs NR NR (disopyramide, procainamide, quinidine only) Pharmacological class: antiasthmatics (theophylline only) NR NR Pharmacological class: anticoagulants (warfarin only) • Increase the anticoagulant effects of warfarin due to • Another histamine (H2) receptor inhibition of warfarin metabolism; antagonist • Bleeding. Pharmacological class: antiepileptics (carbamazepine only) • Cimetidine inhibits the hepatic metabolism of most NR drugs in the central nervous system; • Aggravate adverse reactions. Pharmacological class: antiepileptics (phenytoin only) NR NR Pharmacological class: benzodiazepines • Cimetidine inhibits the hepatic metabolism of most NR drugs in the central nervous system; • Aggravate adverse reactions. Pharmacological class: calcium channel blockers NR NR (nifedipine only) Pharmacological class: selective serotonin reuptake NR NR inhibitors (fluvoxamine only) Pharmacological class: tricyclic antidepressants • Cimetidine inhibits the hepatic metabolism of most NR drugs in the central nervous system; • Aggravate adverse reactions. Pharmacological Classes Non-steroidal anti-inflammatory > 2 drugs in the pharmacological class of non-steroidal anti- • Adverse drug reactions; • Paracetamol. inflammatory • No evidence of benefit to the association of drugs. Pharmacological class: angiotensin converting enzyme • Deterioration of renal function; • Paracetamol. inhibitors • Hyperkalemia. Pharmacological class: angiotensin II receptor antagonists • Deterioration of renal function; NR
• Hyperkalemia. Pharmacological class: angiotensin receptor blockers • Renal failure. • Paracetamol. Pharmacological class: anticoagulants (warfarin only) • Increase anticoagulant activity and bleeding; NR • Non-steroidal anti-inflammatory drugs decrease platelet function and cause gastrointestinal disorders (e.g. gastrointestinal bleeding). Pharmacological class: antihypertensives • Edema; • Assess the need for anti-inflammatory • Worse of arterial hypertension; drugs; • Heart failure; • Paracetamol. • Decreased antihypertensive effect. Pharmacological class: antiplatelet agent • Peptic ulcer. NR Pharmacological class: corticosteroids • Peptic ulcer. • Paracetamol; • Use gastric protection; • Monitor kidney function and high blood pressure. Pharmacological class: corticosteroids (dexamethasone, • Bleeding. NR hydrocortisone, methylprednisolone, prednisolone only) Pharmacological class: digitalis (digoxin only) • Toxicity. NR Pharmacological class: direct thrombin inhibitors • Severe gastrointestinal bleeding. NR Pharmacological class: diuretics • Reduction of diuretic action; • Paracetamol; • Aggravate of heart failure. • Use gastric protection; • Monitoring of kidney function and high blood pressure. Pharmacological class: factor Xa inhibitors • Severe gastrointestinal bleeding. NR Pharmacological class: glucocorticoids • Bleeding; NR • Fluid retention. Pharmacological class: loop diuretics • Nephrotoxicity. NR Pharmacological class: mood stabilizers (lithium only) NR • Paracetamol; • Opioids; • Monitor lithium levels. Pharmacological class: selective norepinephrine reuptake • Bleeding. • Paracetamol; inhibitors • Use of gastric protection; • Monitor kidney function and high blood pressure.
Pharmacological class: selective serotonin uptake inhibitors • Bleeding. • Paracetamol; • Use gastric protection; • Monitor kidney function and high blood pressure. Pharmacological class: thiazides (aliskiren only) • Deterioration of renal function. NR Pharmacological class: vitamin K antagonists NR NR Angiotensin converting enzyme inhibitors > 2 drugs of the pharmacological class inhibitors of NR NR angiotensin converting enzyme Pharmacological class: aldosterone antagonist • Hyperkalemia. NR Pharmacological class: antibiotics (trimethoprim only) • Hyperkalemia. NR Pharmacological class: biguanides • Renal failure; NR • Induce lactacidosis. Pharmacological class: mood stabilizers (lithium only) • Lithium toxicity. NR Pharmacological class: potassium-sparing diuretics • Elevate serum potassium levels; NR • Affect kidney and muscle functions. Pharmacological class: potassium-sparing diuretics (only • Hyperkalemia. • Monitoring the potassium level. amiloride, triamterene) Pharmacological class: potassium-sparing diuretics • Hyperkalemia. NR (spironolactone only) Potassium • Hyperkalemia. NR Monoamine oxidase inhibitors Pharmacological class: anorectic NR NR Pharmacological class: antidepressants NR NR Pharmacological class: antiparkinsonians (levodopa only) NR NR Pharmacological class: antitussives (dextromethorphan NR NR only) Pharmacological class: monoamine oxidase inhibitors NR NR Pharmacological class: selective serotonin reuptake • Adverse drug reactions. NR inhibitors Pharmacological class: opioids (meperidine only) • Serotonergic syndrome. NR Pharmacological class: sympathomimetics NR NR
Pharmacological class: sympathomimetics (dopamine, • Hypertensive crisis. NR ephedrine, phenylephrine only) Platelet antiaggregant > 2 drugs of the pharmacological class of antiplatelet agents • Bleeding. • Anticoagulants; Pharmacological class: vitamin K antagonist NR NR Pharmacological class: vitamin K antagonist • Bleeding. NR (acenocoumarol only) Pharmacological class: anticoagulants (warfarin only) • Bleeding. NR Pharmacological class: non-steroidal anti-inflammatory • Bleeding. • Paracetamol; • Weak anti-inflammatory drugs, such as low-dose ibuprofen, are preferable; • Use gastric protection; • Monitoring of kidney function and blood pressure Pharmacological class: direct thrombin inhibitors • No evidence of benefit to the association of drugs. NR Pharmacological class: factor Xa inhibitors • No evidence of benefit to the association of drugs. NR NR: Not reported.
Table 7. Potentially inappropriate interactions between potentially inappropriate drugs and morbidities/syndromes classified according to the International Statistical Classification of Diseases and Related Health Problems – 10th revision. Medication/ Morbidities/ Reason, risks, and adverse drugs Pharmacological N Therapeutic Management Syndromes events Classes Non-steroidal Chronic kidney 17 • Kidney failure; • Paracetamol; anti-inflammatory failure • Acute kidney damage; • Weak opioid (e.g. tramadol); • Decline in kidney function; • Topical capsaicin; • Reduced kidney blood flow; • Lidocaine patch; • Water and sodium retention. • Corticosteroids; • Metamizole (dipyrone) (500-100mg); • Monitor of renal function; • Non-pharmacological treatment (e.g., physiotherapy, acupuncture, thermotherapy, electrostimulation, and therapeutic massage). Metoclopramide Parkinson's 13 • Worse Parkinson's disease; • Domperidone; disease • Increase extrapyramidal symptoms • Non-pharmacological therapy; causing anti-dopaminergic and cholinergic effects. Non-steroidal Ulcer 13 • Cause or aggravate ulcers, • Paracetamol; anti-inflammatory bleeding, or perforation. • Ibuprofen; • Weak opioid (e.g. tramadol); • Selective COX-2 inhibitor, associated with gastric protection. Anticholinergics Dementia 13 • Induce or worse dementia; • Consider drugs without anticholinergic activity; • Adverse events in the central • For allergies: second-generation antihistamine, nasal steroid; nervous system; • For Parkinson's diseases: levodopa with carbidopa. • Worse cognitive impairment. Non-steroidal Cardiac 12 • Fluid and salt retention; • Paracetamol; anti-inflammatory insufficiency • Worse heart failure, high blood • Weak opioid (e.g. tramadol); pressure and edema. • Metamizole (dipyrone) (500-1000mg); • Monitoring of cardiovascular function; • Non-pharmacological treatment (e.g., physiotherapy, acupuncture, thermotherapy, electrostimulation, and therapeutic massage). Non-steroidal Hypertension 11 • Fluid and salt retention; • Paracetamol; anti-inflammatory • Exacerbation of high blood • Metamizole (dipyrone) (500-1000mg); pressure and edema. • Non-pharmacological treatment (e.g., physiotherapy, acupuncture, thermotherapy, electrostimulation, and therapeutic massage).
Antipsychotics Parkinson's 10 • Aggravate extrapyramidal, • Domperidone; disease antidopaminergic, cholinergic • Quetiapine; effects, and Parkinson’s disease. • Clozapine. Benzodiazepines Falls and 10 • Ataxia; • For anxiety: buspirone or norepinephrine and serotonin reception Fractures • Impaired psychomotor function; inhibitors; • Syncope; • For absence of safer alternatives: evaluate the reduction in use and • Falls. implement other strategies to reduce the risk of falling. Antipsychotics Dementia 10 • Ataxia; • Selective serotonin reuptake inhibitors (except fluoxetine); • Impaired psychomotor function, • Noradrenaline and serotonin reuptake inhibitors. additional falls; • Pro-arrhythmic effect (syncope induction and changes in the QT interval); • Orthostatic hypotension; • Bradycardia. Tricyclic Glaucoma 8 • Aggravate of glaucoma, due to the • Selective serotonin reuptake inhibitors antidepressants anticholinergic effect. Anticholinergics Constipation 8 • Intestinal obstruction; • Osmotic laxative. • Orthostatic hypotension. Tricyclic Benign prostatic 8 • Worse benign prostatic • Selective serotonin reuptake inhibitors (except fluoxetine); antidepressants hyperplasia hyperplasia; • Noradrenaline and serotonin reuptake inhibitors. • Retention or urinary incontinence. Tricyclic Syncope 7 • Ataxia; • Selective serotonin reuptake inhibitors (except fluoxetine); antidepressants • Impaired psychomotor function; • Noradrenaline and serotonin reuptake inhibitors. • Pro-arrhythmic effects, change in the QT interval; • Syncope; • Falls; • Orthostatic hypotension; • Bradycardia. Tricyclic Falls and 7 • Impaired psychomotor function; • Selective serotonin reuptake inhibitors (except fluoxetine); antidepressants Fractures • Ataxia; • Noradrenaline and serotonin reuptake inhibitors. • Syncope; • For depression: bupropion; • Falls. • For neuropathic pain: gabapentin, pregabalin, topical capsaicin and lidocaine adhesive. Antipsychotics Falls and 7 • Impaired psychomotor function; • For depression: the short-term use of antipsychotics (e.g. haloperidol, Fractures • Ataxia; quetiapine);
• Syncope; • For complications: behavioral dementia preferable low-dose non- • Falls. anticholinergic drugs (e.g. risperidone, quetiapine); • In the absence of safer alternatives, evaluate the reduction in use and implement other strategies to reduce the risk of falling.
Table 8. Potentially inappropriate interaction (drug/pharmacological class), according three respiratory diseases classified according to the International Statistical Classification of Diseases and Related Health Problems – 10th revision. Chronic obstructive Respiratory Drug/Pharmacological Class Asthma pulmonary disease failure Antiasthmatics 0 1 0 Antitussives 0 1 0 Benzodiazepines 2 4 2 Beta-blockers 5 6 0 Chlorazepate 0 2 0 Chlordiazepoxide 0 1 0 Diazepam 0 2 0 Halazepam 0 1 0 Metformin 0 0 1 Mucolytics 1 1 0 Non-selective beta-blockers 1 1 0 Propanolol 0 1 0 Quazepam 0 1 0 Selective beta-blockers 1 1 0 Systemic corticosteroids 0 1 0 Total of instruments cited interaction 10 24 3
Table 9. Potentially inappropriate interaction (drug/pharmacological class), according six mental and behavioral disorders classified according to the International Statistical Classification of Diseases and Related Health Problems – 10th revision. Drug/Pharmacological Anorexi Cognitive Depressio Delirium Dementia Insomnia Class a Impairment n Alprazolam 0 1 1 1 0 0 Amitriptyline 0 1 1 2 0 0 Amphetamines 0 0 0 0 0 2 Anticholinergics 0 5 6 13 0 0 Anticholinesterases 0 1 0 0 0 0 Anticonvulsants 0 1 0 0 0 0 Antidepressants 0 0 0 1 0 0 Antihistamines 0 0 0 1 0 0 Antimuscarínicos 0 3 1 4 0 0 Antispasmodics 0 1 0 0 0 0 Anti-Ulcer 0 1 1 2 0 0 Atropine 0 1 0 1 0 0 Atypical Antipsychotics 0 4 3 10 0 5 Barbiturates 0 0 0 2 0 0 Benzodiazepines 0 3 2 5 3 0 Biperiden 0 1 0 3 0 0 Caffeine 0 0 0 0 0 2 Carisoprodol 0 1 0 1 0 0 Chlorazepate 0 1 1 1 0 0 Chlordiazepoxide 0 2 2 2 0 0 Cimetidine 0 1 2 1 0 0 Clomipramine 0 1 2 2 0 0 Clonazepam 0 1 1 1 0 0 Clozapine 0 1 1 0 0 0 Corticosteroids 0 0 3 0 0 0 Cyclobenzaprine 0 2 1 2 0 0 Darifenacin 0 0 0 1 0 0 Dextroamphetamine 1 1 0 0 0 0 Diazepam 0 2 2 2 0 0 Dicyclomine 0 0 0 1 0 0 Drugs Z 0 0 0 1 0 0 Estazolam 0 1 1 1 0 0 Eszopiclone 0 1 1 1 0 0 Famotidine 0 1 2 1 0 0 Femproporex 0 0 0 0 0 1 Fentanyl 0 0 0 1 0 0 Fluoxetine 3 0 0 0 0 0 Flurazepam 0 2 2 2 0 0 Guanetidine 0 0 0 0 1 0 Haloperidol 0 1 1 1 0 0 Homatropin 0 1 0 1 0 0 Hyosomycin 0 1 0 1 0 0 Imipramine 0 1 1 2 0 0 Lorazepam 0 2 1 1 0 0 Mazindol 0 0 0 0 0 1 Meperidine 0 1 2 1 0 0 Methyldopa 0 0 0 0 4 0 Methylphenidate 4 3 0 0 2 1 Morphine 0 0 0 1 0 0 Muscle relaxers 0 4 0 0 0 0
Nizatidine 0 1 2 1 0 0 Nortriptyline 0 1 1 1 0 0 Olanzapine 0 1 1 0 0 0 Opioids 0 0 0 1 0 0 Orphenadrine 0 2 1 2 0 0 Oxybutynin 0 1 0 3 0 0 Pemoline 1 1 0 0 0 0 Perfenazine 0 1 1 1 0 0 Ranitidine 0 1 2 1 0 0 Reserpinum 0 0 0 0 1 0 Scopolamine 0 1 0 1 0 0 Sibutramine 0 0 0 0 0 1 Solifenacin 0 0 0 1 0 0 Tizanidine 0 1 0 2 0 0 Triazolam 0 0 1 1 0 0 Tricyclic antidepressants 0 0 0 7 0 0 Triexiphenidyl 0 1 0 2 0 0 Tropatepine 0 0 0 1 0 0 Typical Antipsychotics 0 4 3 10 0 5 Zaleplom 0 1 1 1 0 0 Zolpidem 0 3 3 3 0 0 Total of instruments cited 9 75 57 58 11 18 interaction
Table 10. Reasons, therapeutic management for potentially inappropriate interaction (drug/pharmacological class), according six mental and behavioral disorders classified according to the International Statistical Classification of Diseases and Related Health Problems – 10th revision. Drug/Pharmacological Class Reasons, risks, and adverse drugs events Proposal of therapeutic management Anorexia Pharmacological class: central nervous system • Appetite suppression (1). • NR stimulants (dextroamphetamine only) Pharmacological class: central nervous system • Appetite suppression (1–4). • Discontinue (4) stimulants (methylphenidate only) Pharmacological class: central nervous system • Appetite suppression (1). • NR stimulants (pemoline only) Pharmacological class: selective serotonin reuptake • Appetite suppression (1–3). • SNRI; inhibitors (fluoxetine only) • SSRI (3). Cognitive impairment Pharmacological class: anticholinergics • Adverse events in the central nervous system; • Discontinue; • Induce or worse cognitive impairment (4–8). • Non-pharmacological therapy. • Another pharmacological class with the same indication and with less or no anticholinergic activity (4,8).
Pharmacological class: anticholinergics (biperiden, • Adverse drug events in the central nervous system • NR oxybutynin, homatropin, triexiphenidyl only) (9). Pharmacological class: anticholinesterases • Affect cognitive function (2). • NR Pharmacological class: anticonvulsants • Stroke; • Avoid use in the elderly, unless the elderly is • Mortality (9). causing harm to themselves or others and non- pharmacological alternatives are not possible or effective (9). Pharmacological class: tricyclic antidepressants • Adverse drug events in the central nervous system; • NR (amitriptyline, clomipramine, imipramine only) • Cognitive impairment (9). Pharmacological class: tricyclic antidepressants • Adverse drug events in the central nervous system; • NR (nortriptyline only) • Cognitive impairment (9). Pharmacological class: antispasmodics • Adverse drug events in the central nervous system; • A • Worse cognitive impairment (1,10). Pharmacological class: antispasmodics (dicyclomine • Adverse drug events in the central nervous system • NR only) (9). Pharmacological class: antihistamines • Adverse events in the central nervous system; • NR • Worsening of cognitive impairment (1,4,10)
Pharmacological class: antimuscarinics • Confusion; • NR • Agitation (11–13).
Pharmacological class: antimuscarinics (atropine, • Adverse drug events in the central nervous system • NR scopolamine, hyosomycin only) (9). Pharmacological class: atypical and typical • Stroke • Avoid use in the elderly, unless the elderly is antipsychotics • Mortality causing harm to themselves or others and non- • Induce or worse cognitive impairment (1,6,7,14). pharmacological alternatives are not possible or effective (1,7). Pharmacological class: atypical and typical • NR (15) • NR antipsychotics (clozapine, haloperidol, olanzapine, perfenazine only) Pharmacological class: anti-ulcer (H2 type histamine • Inducing or worsening of cognitive impairment (7). • NR receptors) Pharmacological class: anti-ulcer (h₂ type histamine • Adverse drug events in the central nervous system • NR receptors): (cimetidine, famotidine, nizatidine, (9). ranitidine, only) Pharmacological class: benzodiazepines • Adverse drug events in the central nervous system • Discontinue; (1,4,7). • Non-pharmacological therapy (4). Pharmacological class: benzodiazepines: • NR (15) • NR (alprazolam, chlorazepate, diazepam, Chlordiazepoxide, flurazepam, triazolam) Pharmacological class: benzodiazepines • Adverse drug events in the central nervous system • NR (clonazepam, chlordiazepoxide, diazepam, (9). estazolam, flurazepam, lorazepam only) Pharmacological class: drugs z (zaleplom, • Adverse drug events in the central nervous system • NR eszopiclone, zolpidem only) (5). Pharmacological class: drugs Z (zolpidem only) • Adverse drug events in the central nervous system; • NR • Induce or worse cognitive impairment (7,9). Pharmacological class: central nervous system • Adverse drug events in the central nervous system • NR stimulants (dextroamphetamine only) (1). Pharmacological class: central nervous system • Adverse drug events in the central nervous system; • Discontinue; stimulants (methylphenidate only) • Worse cognitive impairment (1,2,4). • Non-pharmacological therapy (4). Pharmacological class: central nervous system • Adverse drug events in the central nervous system • NR stimulants (pemoline only) (1); Pharmacological class: opioids (meperidine only) • Inducing or worsening of cognitive impairment (7). • NR Pharmacological class: Muscle relaxers • Adverse drug events in the central nervous system. • NR
• Sedative or anticholinergic adverse reactions (1,2,4,5). Pharmacological class: Muscle relaxers • Adverse drug events in the central nervous system • NR (carisoprodol, cyclobenzaprine, orphenadrine, (9). Tizanidine only) Pharmacological class: Muscle relaxers (only • Decreasing of urinary flow; • Non-pharmacological treatment (i.e. cyclobenzaprine and orphenadrine) • Urinary retention (16). physiotherapy, acupuncture, thermotherapy, electrostimulation and therapeutic massage) (16). Delirium Pharmacological class: anticholinergics • Induce or exacerbate delirium (1,6,7,12,17,18). • NR Pharmacological class: tricyclic antidepressants • NR • NR (amitriptyline only) Pharmacological class: tricyclic antidepressants • Induce or exacerbate delirium (15,17) • NR (clomipramine only) Pharmacological class: tricyclic antidepressants • NR (15) • NR (imipramine only) Pharmacological class: tricyclic antidepressants • Induce or exacerbate delirium (17). • NR (nortriptyline only) Pharmacological class: antimuscarinics • Induce or exacerbate delirium (12,18). • NR Pharmacological class: atypical and typical • Induce or exacerbate delirium (1,6,7) • Avoid use in the elderly, unless the elderly is antipsychotics causing harm to themselves or others and non- pharmacological alternatives are not possible or effective (1,7). Pharmacological class: atypical and typical • NR (15) • NR antipsychotics (clozapine, haloperidol, olanzapine, perphenazine only) Pharmacological class: anti-ulcer (H2 type histamine • Induce or exacerbate delirium (7). • NR receptors) Pharmacological class: anti-ulcer (H2 type histamine • Induce or exacerbate delirium (17). • NR receptors): (cimetidine, famotidine, nizatidine, ranitidine only) Pharmacological class: benzodiazepines • Induce or exacerbate delirium (5,7). • NR Pharmacological class: benzodiazepines: • NR (15) • NR (alprazolam, Chlorazepate, diazepam, Chlordiazepoxide, flurazepam, triazolam only)
Pharmacological class: benzodiazepines: • Induce or exacerbate delirium (17). • NR (clonazepam, chlordiazepoxide, diazepam, estazolam, flurazepam, lorazepam only) Pharmacological class: corticosteroids • Induce or exacerbate delirium (5,16,17). • Non-pharmacological treatment (for example, physiotherapy, acupuncture, thermotherapy, electrostimulation and therapeutic massage) (16). Pharmacological class: drugs z (zaleplom, • Induce or exacerbate delirium (5). • NR eszopiclone, zolpidem only) Pharmacological class: drugs z (zolpidem only) • Induce or exacerbate delirium (7,9). • NR Pharmacological class: Opioids (Meperidine only) • Induce or exacerbate delirium (7,16). • Non-pharmacological treatment (for example, physiotherapy, acupuncture, thermotherapy, electrostimulation and therapeutic massage) (16). Pharmacological class: Muscle relaxers • Induce or exacerbate delirium (16). • Non-pharmacological treatment (for example, (Cyclobenzaprine, Orphenadrine only) physiotherapy, acupuncture, thermotherapy, electrostimulation and therapeutic massage) (16). Dementia Pharmacological class: anticholinergics • Worsening of cognitive impairment; • To consider another pharmacological class • Adverse events in the central nervous system; with the same indication and with less or no • Induce or exacerbate dementia (2,3,19–21,5–8,11– anticholinergic activity. 13,18). • For allergies: second-generation antihistamine, nasal steroid; • For Parkinson's disease levodopa with carbidopa (8,20). Pharmacological class: anticholinergics (biperiden • Worse cognitive impairment (3,9,19). • Use of another antiparkinsonian drug (3). only) Pharmacological class: anticholinergics (darifenacin, • Confusion; • NR solifenacin only) • Agitation (22). Pharmacological class: anticholinergics (homatropin • Adverse drug events in the central nervous system • NR only) (9). Pharmacological class: anticholinergics (Oxybutynin • Confusion; • NR only) • Agitation (4,9). Pharmacological class: anticholinergics • Worsening of cognitive impairment. • NR (triexiphenidyl only) • Adverse drug events in the central nervous system (19,22).
Pharmacological class: anticholinergics (tropatepine • Worsening of cognitive impairment (19). • NR only) Pharmacological class: anticholinergics • Adverse drug events in the central nervous system • NR (orphenadrine only) (9). Pharmacological class: antidepressants • Limited action for depression in patients with • NR dementia (23). Pharmacological class: tricyclic antidepressants • Worse cognitive impairment; • For depression: SSRI and bupropion. • Induce or exacerbate dementia (11–13,20–22,24). • For neuropathic pain: SNRI, gabapentin, pregabalin, topical capsaicin, lidocaine adhesive (20). Pharmacological class: tricyclic antidepressants • Adverse drug events in the central nervous system; • NR (amitriptyline, clomipramine, imipramine only) • Cognitive impairment (9,15). Pharmacological class: tricyclic antidepressants • Adverse drug events in the central nervous system; • NR (nortriptyline only) • Cognitive impairment (9). Pharmacological class: Antispasmodics • Adverse drug events in the central nervous system • NR (dicyclomine only) (9). Pharmacological class: Antihistamines • Adverse drug events in the central nervous system • NR (9). Pharmacological class: Antimuscarinics • Worsening of cognitive impairment (11–13,18). • NR Pharmacological class: Antimuscarinics (atropine, • Adverse drug events in the central nervous system • NR scopolamine, hyosomycin only) (9). Pharmacological class: atypical and typical • Worse the patient's cognitive status; • Atypical antipsychotics: risperidone, antipsychotics • Stroke; olanzapine, aripiprazole, quetiapine • Mortality; • Avoid use in the elderly, unless the elderly is • Induce or exacerbate dementia causing harm to themselves or others and non- (3,6,7,11,13,17,19,20,25). pharmacological alternatives are not possible or effective (1,3,7,17,20).
Pharmacological class: atypical and typical • NR (15) • NR antipsychotics (haloperidol, perphenazine only) Pharmacological class: anti-ulcer (h₂ type histamine • Induce or exacerbate dementia (20). • Proton pump inhibitors (20). receptors) Pharmacological class: anti-ulcer (h₂ type histamine • Adverse events in the central nervous system (17). • NR receptors): (cimetidine, famotidine, nizatidine, ranitidine only) Pharmacological class: Barbiturates • NR (3,21) • NR
Pharmacological class: benzodiazepines • Adverse events in the central nervous system; • Short-term use of low doses of • Induce or exacerbate dementia (1,3,7,20,21). benzodiazepines. • For anxiety: buspirone, SSRI and SNRI (3,20). Pharmacological class: benzodiazepines: • NR (15) • NR (alprazolam, chlorazepate, diazepam, chlordiazepoxide, flurazepam, triazolam only) Pharmacological class: benzodiazepines: • Adverse drug events in the central nervous system • NR (clonazepam, chlordiazepoxide, diazepam, (9). estazolam, flurazepam, lorazepam only) Pharmacological class: drugs Z • NR (20) • NR Pharmacological class: drugs Z (Eszopiclone only) • Adverse drug events in the central nervous system • NR (5). Pharmacological class: drugs Z (zaleplom, zolpidem • Adverse drug events in the central nervous system • NR only) (5). Pharmacological class: drugs Z (zolpidem only) • Adverse drug events in the central nervous system • NR (7,9). Pharmacological class: Opioids • Worsening of cognitive impairment (9). • Use only in palliative care or management of moderate to severe chronic pain (9). Pharmacological class: Opioids (fentanyl only) • Worsening of cognitive impairment (2). • NR Pharmacological class: Opioids (meperidine only) • Induce or exacerbate dementia (7). • NR Pharmacological class: Opioids (morphine only) • Worse cognitive impairment (2). • NR Pharmacological class: Muscle relaxers • Adverse drug events in the central nervous system • NR (carisoprodol, cyclobenzaprine, orphenadrine, (9). tizanidine only) Pharmacological class: Muscle relaxers • Adverse drug events in the central nervous system • Non-pharmacological treatment (for example, (cyclobenzaprine, orphenadrine only) (16). physiotherapy, acupuncture, thermotherapy, electrostimulation and therapeutic massage) (16). Depression Pharmacological class: antihypertensive drugs • Risk of induce or exacerbate depression (1,3,4,10). • Another pharmacological class of (methyldopa only) antihypertensive drugs (3,4). Pharmacological class: benzodiazepines. • Risk of induce or exacerbate depression (1–3). • Short-term use of low doses of benzodiazepines (3). Pharmacological class: central nervous system • Risk of induce or exacerbate depression (2,3). • NR stimulants (methylphenidate only) Guanetidina • Risk of induce or exacerbate depression (1). • NR
Reserpinum • Risk of induce or exacerbate depression (1,3,4). • Another pharmacological class of antihypertensive drugs (3,4). Insomnia Pharmacological class: Amphetamines • Stimulate effects on the central nervous system (1,4). • Discontinue (4). Pharmacological class: central nervous system • Stimulate effects on the central nervous system (7). • NR stimulants (methylphenidate only) Pharmacological class: central anorectic • Stimulate effects on the central nervous system (2). • NR (femproporex; mazindol; sibutramine only) Pharmacological class: atypical and typical • Risk of mental confusion; • Discontinue; antipsychotics • Hypotension; • Non-pharmacological therapy (4). • Extrapyramidal adverse reactions; • Falls; • Stimulate effects on the central nervous system (1– 4). Caffeine • Stimulate effects on the central nervous system (7,9). • NR NR: Not reported; SNRI: Serotonin and norepinephrine reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors
Table 11. Potentially inappropriate medications with adverse drug reactions in the mental and behavioral disorders. Drug/pharmacological Reasons Proposal of therapeutic management class • Inappropriate in doses greater than 2mg per day; • BZD (short or intermediate half-life); • Falls due muscle relaxing effect and possible hip fracture; • Valerian; • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Sedative antidepressants (trazodone, mianserin, psychosis); mirtazapine); • Depression. • Zolpidem (≤ 5 mg daily); • Cognitive impairment; • Opipramol; Alprazolam • Delirium; • Low-power neuroleptic drugs (melperone, pipamperon); • Fractures (1,2,6,7,17,26,27). • Non-pharmacological treatment of sleep disorders; • Clinical monitoring of adverse reactions (cognitive function, surveillance, regular history of falls, gait stability test, psychopathology, ataxia); • Avoid or use the lowest possible dose, up to half the usual dose, reduce and decrease (1,2,6,26,27). • Stroke; • Avoid, unless non-pharmacological options (for example, behavioral interventions) have failed or are not possible Amisulpride • Cognitive impairment; • Mortality (6). and the elderly person is threatening substantial harm to himself or others (6). • Adverse anticholinergic effects at the peripheral level (constipation, • SNRI; dry mouth, hypotension, arrhythmia) and at the central level • SSRI; (confusion, delirium, drowsiness, restlessness), • Non-pharmacological treatments (2,14,26,27,29,30). • Cognitive impairment. • Falls due muscle relaxing effect and possible hip fracture; • Psychiatric reactions (e.g., agitation, irritability, hallucinations, Amitriptyline psychosis); • Depression; • Orthostatic hypotension; • Exacerbate of urinary symptoms; • Prolongation of the QT interval; • Sudden cardiac death; • Urinary retention (2,14,26–32). • Agitation; • Decreased medication dosage; • Delirium; • Reassessment of the need for treatment (33). Anticholinergics • Cognitive impairment; • Worse glaucoma;
• Partial or complete gastrointestinal obstruction (33,34). • Anticholinergic adverse reactions; • NR • Urinary retention; • Cognitive impairment; • Glaucoma; Antihistamines • Orthostatic hypotension; • Falls; • Arrhythmias (prolongation of the QT interval); • Dry mouth (34). • Anticholinergic adverse reactions; NR • Restlessness; Antimuscarinic • Delirium; antagonists • Urinary retention; • Cognitive impairment (34). • Anticholinergic adverse reactions (urinary retention, constipation, • Atypical antipsychotics (34); visual disturbances); • Cognitive impairment; • Orthostatic hypotension; Antipsychotics • Sedation; • Extrapyramidal symptoms including Parkinson-like symptoms; • Dystonia; • Akathisia; • Tardive dyskinesia (34). • Extrapyramidal effects; • Use only if absolutely necessary (31). • Super sedation; • Cognitive impairment; Aripiprazole • Cerebrovascular disorders; • Mortality. • Stroke in people with dementia (6,31,32). • Extrapyramidal and anticholinergic effects; • Use only in acute psychotic episodes; • Hypotonia; • Monitor neurological and cardiovascular function (32). Asenapine • Sedation; • High doses increase the risk of stroke in people with dementia (32).
• Anticholinergic effects (dry mouth, constipation, urinary retention, • Pinaverio (32). mydriasis, tachycardia, drowsiness, agitation, confusion, delirium, hallucinations); Belladonna • Prolongation of the QT interval; • Ventricular arrhythmia; • Sudden cardiac death (32). • Delirium; • NR Benzodiazepines • Falls and fractures; • Cognitive impairment (25). • Extrapyramidal effects; • Levodopa (31). • Super sedation; Biperiden • Cognitive impairment; • Cerebrovascular disorders; • Mortality (31). • Inappropriate doses greater than 1,5mg per day; • BZD (short or intermediate half-life); • Falls due muscle relaxing effect and possible hip fracture; • Drugs Z: zolpidem, zopiclone or zaleplom in low doses; • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Sedative antidepressants; psychosis); • Low-potency neuroleptics; Bromazepam • Depression. • Valerian; • Cognitive impairment; • Non-pharmacological interventions; • Delirium; • Monitor adverse reactions (2,6,7,26,27,32). • Fractures (2,6,7,17,26,27,32). • Anticholinergic effects (dry mouth, constipation, urinary retention, • Second generation antihistamines (e.g. cetirizine, mydriasis, tachycardia, drowsiness, agitation, confusion, delirium, desloratadine, loratadine) (32). hallucinations); Bronfeniramine • Prolongation of the QT interval; • Ventricular arrhythmia; • Sudden cardiac death (32). • Falls due muscle relaxing effect and possible hip fracture; • BZD (short or intermediate half-life); • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Drugs Z: zolpidem, zopiclone or zaleplom in low doses; psychosis); • Sedative antidepressants; Brotizolam • Depression; • Low-potency neuroleptics; • Cognitive impairment (26). • Valerian; • Non-pharmacological interventions; • Monitor adverse reactions (26). • Adverse drug reactions of the central nervous system (sedation and • Hydromorphone (34). Bumetanide delirium);
• Adverse drug reactions in the gastrointestinal (nausea and constipation); • Anticholinergics effects (34). • Hallucination; • Levodopa; Cabergoline • Delirium; • Another dopamine agonist (32). • Fibrosis of the heart valve (32). • Risk of decreased bone mineral density; • Lamotrigine; • Fractures; • Levetiracetam (32). Carbamazepine • Hyponatremia; • Cognitive impairment; • Gait disorders (32). • Risk of anticholinergic effects (dry mouth, constipation, urinary • Second generation antihistamines (e.g. cetirizine, retention, mydriasis, tachycardia, drowsiness, agitation, confusion, desloratadine, loratadine) (32). delirium, hallucinations); Carbinoxamine • Prolongation of the QT interval; • Ventricular arrhythmia; • Sudden cardiac death (32). • Falls due muscle relaxing effect and possible hip fracture; • BZD (short or intermediate half-life); • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Drugs Z: zolpidem, zopiclone or zaleplom in low doses; psychosis); • Sedative antidepressants; • Depression; • Low-potency neuroleptics (eg melperone, pipamperon); Chlorazepate • Cognitive impairment; • Valerian; • Delirium; • Clinical monitoring of adverse reactions (cognitive • Fractures (5,26,32). function, vigilance, regular history of falls, gait firmness test, psychopathology, ataxia) (5,26,32); • Withdrawal problems; • BZD (short or intermediate half-life); • Daytime sedation; • Drugs Z: zolpidem, zopiclone or zaleplom in low doses; • Falls due muscle relaxing effect and possible hip fracture; • Opipramol; • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Sedative antidepressants (e.g. mirtazapine); Chlordiazepoxide psychosis); • Low-potency neuroleptics (e.g. melperone, pipamperon); • Depression; • Clinical monitoring of adverse reactions (cognitive • Cognitive impairment; function, vigilance, regular history of falls, gait firmness • Delirium; test, psychopathology, ataxia) (1,26,32,35) • Fractures (1,2,7,10,17,26,32). • Cognitive impairment; • NR Chlordiazepoxide + • Delirium; amitriptyline • Falls and fractures (5).
• Anticholinergic effects (eg, constipation, dry mouth, visual • Second generation antihistamines (e.g., cetirizine, disturbance, bladder dysfunction, confusion, sedation); loratadine, desloratadine); • Cognitive impairment; • Monitor the anticholinergic effects; Chlorpheniramine • Prolongation of the QT interval; • Monitor ECG; • Delirium; • Discontinue treatment 1 day before surgery • Enhance the sedative effect of general anesthetics (26,27,30–32,36). (26,27,30,31,36). • Anticholinergic effects (drowsiness, confusion and cognitive • Non-phenothiazine neuroleptics with less anticholinergic impairment); activity (clozapine, risperidone, olanzapine, amisulpride, • Extrapyramidal effects; quetiapine); • Hypotension; • Olanzapine and quetiapine are contraindicated for Chlorpromazine • Sedation; diabetes; • Falls; • Meprobamate; • Stroke and mortality in patients with dementia (2,7,10,31). • Haloperidol should not be used for more than 3 days; • Use when absolutely necessary (2,10,31). • Extrapyramidal effects; • Non-phenothiazine neuroleptics with less anticholinergic • Anticholinergic effects; activity (clozapine, risperidone, olanzapine, amisulpride, Chlorprothixene • Hypotension, sedation; quetiapine);
• Falls; • Meprobamate; • Stroke and mortality in patients with dementia (2). • Haloperidol should not be used for more than 3 days (2). • Effects on the central nervous system; • Proton pump inhibitors; Cimetidine • Confusion; • Anti-H2 (ranitidine, famotidine, nizatidine) (4,6). • Delirium (4,6,36). • Asthenia; • Betahistine (32). • Gastrointestinal disorders; Cinnarizine • Extrapyramidal motor signals; • Depression (32). • Anticholinergic effects (e.g., constipation, dry mouth); • Second generation antihistamines (e.g., cetirizine, Clemastine • Cognitive impairment; loratadine, desloratadine); • Prolongation of the QT interval (26). • Monitoring of the anticholinergic effects (26).
• Falls due muscle relaxing effect and possible hip fracture; • BZD (short or intermediate half-life); • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Drugs Z: zolpidem, zopiclone or zaleplom in low doses; psychosis); • Opipramol; • Depression; • Sedative antidepressants (e.g. mirtazapine); • Cognitive impairment; • Low-potency neuroleptics (e.g. melperone, pipamperon); Clobazam • Delirium; • Clinical monitoring of adverse reactions (cognitive • Falls and fractures (2,6,7,17,26,27,32). function, vigilance, regular history of falls, gait firmness test, psychopathology, ataxia) (2,6,26,32).
• Adverse anticholinergic effects at the peripheral level (constipation, • SNRI; dry mouth, hypotension, arrhythmia) and at the central level • SSRI (2,27,29,31,32). (confusion, delirium, drowsiness, restlessness); • Bradycardia; • Cognitive impairment; • Falls; • Constipation; Clomipramine • Exacerbation of urinary symptoms; • Urinary retention; • Prolongation in the QT interval; • Arrhythmia; • Mortality; • Avoid in patients with syncope, cognitive impairment, falls, dementia and prostatic hypertrophy (2,25,27,29–32,34). • Adverse anticholinergic effects at the peripheral level (constipation, • For anxiety: BZD (short or intermediate half-life), dry mouth, hypotension, arrhythmia) and at the central level mirtazapine, trazodone, mianserin; (confusion, delirium, drowsiness, restlessness); • For hypnotic indication: zolpidem, zopiclone, valerian; • Cognitive impairment; • Non-pharmacological interventions for anxiety: cognitive- Clonazepam • Falls and fractures; behavioral therapy; • Delirium (1,7,17,27,32,36). • Non-pharmacological interventions for insomnia: sleep hygiene and identify the cause of the sleep disorder; • Use the lowest possible dose and do not exceed 4 weeks (7,27,32). • Disturb the function of the central nervous system causing • Other antihypertensive, for example, angiotensin- depression, cognitive impairment and sedation due to A2 agonist converting enzyme inhibitors, angiotensin receptor Clonidine effects and affecting the autonomic nervous system, causing antagonists, thiazides, beta-blockers, calcium antagonists (long-acting, with peripheral effect);
orthostatic hypotension, bradycardia depression, syncope • Monitor of cardiovascular function and central nervous (10,26,32,34). effects (26,32,34). • Cognitive impairment; • NR Cloxazolam • Delirium; • Falls and fractures (9). • Anticholinergic and extrapyramidal effects (tardive dyskinesia); • Atypical neuroleptics (e.g. risperidone, melperone, • Parkinsonism; pipamperon); • Hypotonia; • Meprobamate; • Sedation; • Haloperidol should not be used for more than 3 days • Falls; • Clinical monitoring of adverse reactions, particularly Clozapine • Increased mortality in patients with dementia; anticholinergic and extrapyramidal reactions, history of • Stroke; fall, neurological and cognitive function (e.g., • Agranulocytosis; parkinsonism); • Myocarditis (7,14,26,32). • Monitoring of cardiovascular function (hypotension, QT interval and blood pressure; • Adjust of the dose, starting with 12.5mg/day (14,26,32). • Gastrointestinal irritation; • NR • Nausea; • Anorexia; Codergocrine • Dizziness; • Redness; • Effectiveness is uncertain, especially in the case of Alzheimer's disease (9,10). • Drowsiness; • Non-pharmacological therapy (physiotherapy, application Cyclobenzaprine • Cognitive impairment; of heat and cold or transcutaneous electrical nerve • Dependence (33). stimulation) (33). • Anticholinergic effects (dry mouth, constipation, urinary retention, • Second generation antihistamines (e.g., cetirizine, mydriasis, tachycardia, drowsiness, agitation, confusion, delirium, loratadine, desloratadine); hallucinations); • Monitoring of anticholinergic effects (27,32); Cyproheptadine • Prolongation of the QT interval; • Ventricular arrhythmia; • Sudden cardiac death (27,32,36). • Anticholinergic effect: constipation (dry mouth, visual disturbance, • Second generation antihistamines (e.g., cetirizine, bladder dysfunction, confusion, sedation); loratadine, desloratadine) (32); Dexchlorpheniramine • Cognitive impairment; • Prolongation of the QT interval; • Ventricular arrhythmia;
• Sudden cardiac death (27,32). • Withdrawal problems; • BZD (short or intermediate half-life); • Daytime sedation; • Drugs Z: zolpidem, zopiclone or zaleplom in low doses; • Cognitive impairment; • Opipramol; • Falls and fractures. • Sedative antidepressants (e.g. mirtazapine); • Anticholinergic effects (e.g., constipation, dry mouth, visual • Low-potency neuroleptics (e.g. melperone, pipamperon); Diazepam disturbance, bladder dysfunction, confusion, sedation); • Clinical monitoring of adverse reactions (cognitive • Prolongation of the QT interval; function, vigilance, regular history of falls, gait firmness • Delirium (1,2,36,6,7,10,17,26,27,31,32). test, psychopathology, ataxia); • Use should be avoided as much as possible. If used, small amounts should be administered for the shortest possible period (6,7,26,27,31,32). • Anticholinergic effects (e.g., constipation, dry mouth); • Second generation antihistamines (e.g., cetirizine, • Cognitive impairment; loratadine, desloratadine); Dimethindene • Prolongation of the QT interval (26). • Monitor adverse reactions, central nervous function and ECG (26). • Adverse anticholinergic effects at the peripheral level (constipation, • Loratadine 10 mg; dry mouth, hypotension, arrhythmia) and at the central level • Cetirizine 10 mg; (confusion, delirium, drowsiness, restlessness); • Fexofenadine 60 mg (27,30,32). • Cognitive impairment; • Falls; Diphenhydramine • Orthostatic hypotension; • Exacerbation of urinary symptoms; • Prolongation of the QT interval; • Sudden cardiac death and urinary retention • Delirium; • Potentiate the sedative effect of general anesthetics (27,30,32,36). • Hallucinations; • NR Dopamine agonist • Delirium (34). • Falls due muscle relaxing effect and possible hip fracture; • SSRI; • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • SNRI; psychosis); • Non-pharmacological treatments, such as behavioral • Depression; therapy; Dosulepin • Cognitive impairment; • Monitoring of anticholinergic effects, suicide; fall risk • Risk of constipation, dry mouth, orthostatic hypotension, arrhythmia, assessment and ECG; falls, drowsiness, confusion, delirium and cognitive impairment • Therapeutic monitoring of drugs if there is a risk of (2,26,27,29,30). intoxication (26,27,29,30).
• Anticholinergic effect (constipation, dry mouth, visual disturbance, • Second generation antihistamines (e.g., cetirizine, bladder dysfunction, confusion, sedation, cognitive impairment); loratadine, desloratadine) (27,32).; Doxylamine • Prolongation of the QT interval; • Ventricular arrhythmia; • Sudden cardiac death (27,32). • Cognitive impairment; • NR Estazolam • Delirium; • Falls and fractures (1,6,17,36). • Cognitive impairment; • Administer a lower dose for a short period; • Depression; • Monitor the possibility of adverse events (6,32); Eszopiclone • Delirium; • Falls and fractures (1,6,32). • Sedation; • It should not be used for long periods; • Cognitive impairment; • The use of benzodiazepines should be avoided as much as Etizolam • Delirium; possible; • Falls and fractures; • If necessary, use in smaller quantities (31). • Loss of motor function (31). • Induce or aggravate the delusion (6,36). • Proton pump inhibitors, use should not be longer than 8 Famotidine weeks; • Use with caution in the perioperative period (6,36). • Dry mouth; • If there is benign prostatic hypertrophy, use with an α1 • Constipation; receptor blocker; Fesoterodine • Exacerbate of urinary symptoms; • When necessary, combine with a laxative (31). • Urinary retention; • Cognitive impairment (31). • Cognitive impairment; • NR Fludiazepam • Confusion; • Falls and fractures (6). • Falls due muscle relaxing effect and possible hip fracture; • BZD (short or intermediate half-life); • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Opipramol; psychosis); • Sedative antidepressants (e.g. mirtazapine); • Depression; • Low-potency neuroleptics (e.g. melperone, pipamperon); Flunitrazepam • Cognitive impairment; • Clinical monitoring of adverse reactions (cognitive • Delirium; function, vigilance, regular history of falls, gait firmness • Fractures (6,7,14,17,26,27,32). test, psychopathology, ataxia); • Non-pharmacological treatment;
• Passionflower; • Lormetazepam (dosages less than 0.5 mg per day); • Brotizolam (dosages less than 0.125 mg per day); • Zolpidem (dosages less than 5 mg per day); • Zopiclone (dosages less than 3.75 mg per day); • Zaleplon (dosages less than 5 mg per day); • Trazodone. • Avoid, if necessary to use the lowest dose for a short period (6,7,14,26,27,32) • Central nervous effects (4,14,26,27,29,30,32,36). • SSRI; • SNRI; • Mirtazapine; • Trazodone; Fluoxetine • Non-pharmacological treatments, such as behavioral therapy; • Clinical monitoring of central nervous function; • Monitor of renal function and serum electrolytes; • Adjust the dose (4,14,26,29,30,32). • Anticholinergic and extrapyramidal effects (tardive dyskinesia); • Avoid, if necessary to use the lowest dose for a short • Parkinsonism; period (6). • Hypotonia; • Sedation; Fluphenazine • Delirium; • Constipation; • Stroke; • Increased mortality in patients with dementia (6,25,26). • Falls due muscle relaxing effect and possible hip fracture; • BZD (short or intermediate half-life); • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Drugs Z: zolpidem, zopiclone or zaleplom in low doses; psychosis); • Opipramol; • Depression; • Sedative antidepressants (e.g. mirtazapine); • Cognitive impairment; Flurazepam • Low-potency neuroleptics (e.g. melperone, pipamperon); • Delirium; • Clinical monitoring of adverse reactions (cognitive • Falls and fractures (1,6,7,10,17,26). function, vigilance, regular history of falls, gait firmness test, psychopathology, ataxia); • Avoid, if necessary to use the lowest dose for a short period (1,6,7,26). Fluvoxamine • Nausea; • SSRI;
• Vomiting; • SNRI; • Drowsiness; • Mirtazapine. • Dizziness; • Dry mouth; • Constipation; • Diarrhea; • Weight loss/anorexia (34). H2 receptor • Delirium; • NR antagonists • Cognitive impairment (31). • Inappropriate doses greater than 2mg per day; • Risperidone; • Anticholinergic and extrapyramidal effects (tardive dyskinesia); • Melperone; • Parkinsonism; • Pipamperon; • Hypotonia; • Clinical monitoring of adverse reactions, particularly • Sedation; anticholinergic and extrapyramidal, history of falls, • Falls; neurological and cognitive function (e.g., parkinsonism); • Stroke; • Monitor of cardiovascular function (hypotension, ECG / • Increased mortality in patients with dementia (2,7,26,31,32). QT interval); Haloperidol • In acute psychosis, short-term use (less than 3 days); • Decrease the use of typical antipsychotic drugs as much as possible; • Use atypical antipsychotics only when absolutely necessary; • Butyrophenones (e.g., haloperidol) are contraindicated for Parkinson's disease. • Olanzapine and quetiapine are contraindicated for diabetes (2,26,31,32); • Sedation; • It should not be used for long periods; • Cognitive impairment; • The use of benzodiazepine should be avoided as much as Haloxazolam • Delirium; possible; • Falls and fractures; • If used, they should be given in small quantities for as • Loss of motor function (31). short a period as possible (31). • Amnesia; • Drugs Z (34). • Ataxia; • Hypotension; Hypnotics • Prolonged sedation; • Falls; • Respiratory depression;
• Cognitive impairment (34). • Neuromuscular block; • Avoid new prescriptions during the perioperative period; Huperzine A • Postoperative delirium (36). • Continue long-term medication with close monitoring (36). • Anticholinergic effects at the peripheral level (constipation, • Second generation antihistamines (e.g., cetirizine, hypotension, arrhythmia) and at the central level (confusion, loratadine, desloratadine); delirium, drowsiness, restlessness); • Monitor anticholinergic effects, central nervous function Hydroxyzine • Cognitive impairment; and ECG (14,26,29,30). • Prolongation of the QT interval; • Falls (14,26,29,30). • Dry mouth; • If there is benign prostatic hypertrophy, use with an α1 • Constipation; receptor blocker; Imidafenacin • Exacerbation of urinary symptoms; • When necessary, combine with a laxative (31). • Urinary retention; • Cognitive impairment (31). • Adverse anticholinergic effects at the peripheral level (constipation, • SSRI; dry mouth, hypotension, arrhythmia) and at the central level • SNRI; (confusion, delirium, drowsiness, restlessness); • Mirtazapine; • Cognitive impairment; • Non-pharmacological treatments, such as behavioral • Falls; therapy; Imipramine • Orthostatic hypotension; • Monitoring of anticholinergic effects, suicide; fall risk • Exacerbation of urinary symptoms; assessment. • Prolongation of the QT interval; • ECG monitoring. • Urinary retention. • Therapeutic monitoring of drugs if there is a risk of • It should be avoided in patients with syncope, cognitive impairment, intoxication (2,26,27,29,31,32). falls, dementia and prostatic hypertrophy (2,25–27,29,31,32). Indomethacin • Adverse reactions in the central nervous system (e.g., delirium) (34). NR • Anticholinergic and extrapyramidal effects (tardive dyskinesia); • Risperidone; • Parkinsonism; • Melperone; • Hypotonia; • Pipamperon; Levomepromazine • Sedation; • Clinical monitoring of adverse reactions, particularly • Stroke; anticholinergic and extrapyramidal, history of falls, • Falls; neurological and cognitive function (eg, parkinsonism); • Increased mortality in patients with dementia (2,14,26,31,32). • Monitor of cardiovascular function (hypotension, ECG / QT interval);
• Non-phenothiazine neuroleptics with less anticholinergic activity (clozapine, risperidone, olanzapine, amisulpride, quetiapine); • Meprobamate; • Administer with caution in cases of renal failure; start with doses of 5 to 10 mg; • Decrease the use of typical antipsychotic drugs as much as possible; • Use atypical antipsychotics only when absolutely necessary; • Butyrophenones (e.g., haloperidol) are contraindicated for Parkinson's disease; • Olanzapine and quetiapine are contraindicated for diabetes (2,14,26,31,32). • Anticholinergic effects at the peripheral level (constipation, • BZD (short or intermediate half-life); hypotension, arrhythmia) and at the central level (confusion, • Valerian; delirium, drowsiness, restlessness); • Sedative antidepressants (trazodone, mianserin, • Cognitive impairment; mirtazapine); • Prolongation of the QT interval; • Zolpidem (≤ 5 mg daily); • Falls and fractures • Opipramol; Lorazepam • Delirium (1,6,7,17,26,27,32,36). • Low-power neuroleptic drugs (melperone, pipamperon); • Non-pharmacological treatment of sleep disorders (sleep hygiene); • Clinical monitoring of adverse reactions (cognitive function, surveillance, regular history of falls, gait stability test, psychopathology, ataxia) (26)(27)(32)(7)(36)(6)(1). • Anticholinergic effects at the peripheral level (constipation, • Valerian; hypotension, arrhythmia) and at the central level (confusion, • Sedative antidepressants (trazodone, mianserin, delirium, drowsiness, restlessness); mirtazapine); • Cognitive impairment; • Zolpidem (≤ 5 mg daily); • Prolongation of the QT interval; • Opipramol; Lormetazepam • Falls (26). • Low-power neuroleptic drugs (melperone, pipamperon); • Non-pharmacological treatment of sleep disorders (sleep hygiene); • Clinical monitoring of adverse reactions (cognitive function, surveillance, regular history of falls, gait stability test, psychopathology, ataxia) (26).
• Anticholinergic effects; • NR Loxapina • Delirium; • Constipation (25). • Anticholinergic effects at the peripheral level (constipation, • SSRI; hypotension, arrhythmia) and at the central level (confusion, • Mirtazapine; delirium, drowsiness, restlessness); • Non-pharmacological treatments, such as behavioral • Cognitive impairment; therapy. Maprotiline • Prolongation of the QT interval; • Monitor of anticholinergic adverse reactions, suicide; fall • Falls (2,26). risk assessment; • ECG monitoring. • Therapeutic monitoring of drugs if there is a risk of intoxication (26). • Anticholinergic effects at the peripheral level (constipation, • BZD (short or intermediate half-life); hypotension, arrhythmia) and at the central level (confusion, • Drugs z: zolpidem, zopiclone, low-dose zaleplon; delirium, drowsiness, restlessness); • Opipramol; • Cognitive impairment; • Sedative antidepressants (e.g. mirtazapine); Medazepam • Prolongation of the QT interval; • Low-potency neuroleptics (e.g. melperone, pipamperon); • Falls and fractures; • Clinical monitoring of adverse reactions (cognitive • Delirium (2,6,26). function , surveillance, regular history of falls, gait firmness test, psychopathology, ataxia) (2,6,26). • Megestrol acetate for the treatment of anorexia in the elderly should • NR Megestrol be limited to cases where other measures have not worked and never as prophylaxis for weight loss (25). • NR • Discontinue and monitor in patients with moderate to Memantine severe dementia, unless memantine has improved clinical status (35). • Seizures; • Paracetamol; • Delirium; • Weak opioids (tramadol, codeine, morphine or • Sedation; hydromorphone); • Confusion; • Metamizole (dipyrone) 500-1000 mg; • Weak non-steroidal anti-inflammatory (e.g. ibuprofen); Meperidine • Dependence; • Withdrawal syndrome; • Clinical monitoring (central nervous function, tendency to • Falls and fractures; fall, cardiovascular function) • Respiratory depression (1,16,25–27,32,34,36). • Monitor of renal function; • Non-pharmacological treatment (for example, physiotherapy, acupuncture, thermotherapy,
electrostimulation and therapeutic massage) (1,16,26,32,34); • Anticholinergic effects (dry mouth, constipation, urinary retention, • Second generation antihistamines (e.g., cetirizine, mydriasis, tachycardia, drowsiness, agitation, confusion, delirium, loratadine, desloratadine) (32). hallucinations); Mequitazine • Prolongation of the QT interval; • Ventricular arrhythmia; • Sudden cardiac death (32). • Orthostatic hypotension; • Preferable 0.1 mg of clonidine at bedtime; do not exceed • Bradycardia; 2.4 mg per day; • Sedation; • Other antihypertensive agents, for example, inhibitors of Methyldopa • Depression; the angiotensin-converting enzyme, antagonists of • Syncope; angiotensin receptors, thiazides, beta-blockers, calcium • Cognitive impairment (1,4,27,34,37,38). antagonists (long-acting, with peripheral effect). • Monitor of cardiovascular function (4,27,37). • Irritability; • SSRI; • Insomnia; • SNRI; Methylphenidate • Tremor; • Short half-life tricyclic antidepressant with no metabolite • Psychomotor agitation; activity (32). • Convulsions (32). • Drowsiness; • Non-pharmacological therapy (physical therapy, Metocarbamol • Cognitive impairment; application of heat and cold or transcutaneous electrical • Dependence (33). nerve stimulation) (33). • Extrapyramidal symptoms; • NR • Cognitive impairment, as a metoclopramide can penetrate the blood- Metoclopramide brain barrier and affect the functions of dopaminergic and cholinergic neurons (10). • Falls due muscle relaxing effect and possible hip fracture; • BZD (short or intermediate half-life); • Psychiatric reactions (eg, agitation, irritability, hallucinations, • Avoid, if necessary, using the lowest dose for a short psychosis); period (2,6). Midazolam • Depression; • Cognitive impairment; • Delirium; • Fractures (2,6,9,36). • Delirium; • NR Muscle relaxant • Falls; • Headache;
• Sedation (34). • Falls due muscle relaxing effect and possible hip fracture; • BZD (short or intermediate half-life); • Psychiatric reactions (eg, agitation, irritability, hallucinations, • Drugs z: zolpidem, zopiclone, low dose zaleplon; psychosis); • Opipramol; • Depression; • Sedative antidepressants (e.g. mirtazapine); • Cognitive impairment; Nitrazepam • Low-potency neuroleptics (e.g. melperone, pipamperon); • Delirium; • Clinical monitoring of adverse reactions (cognitive • Fractures (6,17,26,27) function, surveillance, regular history of falls, gait firmness test, psychopathology, ataxia); • Avoid, if necessary, using the lowest dose for a short (6,26,27). • Effects on the central nervous system; • Proton pump inhibitors, avoid use for more than 8 weeks, Nizatidine • Induce or worsen delirium (6). except in special circumstances (6). • Cognitive impairment; • Avoid, if necessary, using the lowest dose for a short Nordazepam • Confusion; period (6). • Falls and fractures (6). • Adverse anticholinergic effects at the peripheral level (constipation, • SSRI; dry mouth, hypotension, arrhythmia) and at the central level • SNRI; (confusion, delirium, drowsiness, restlessness); • Mirtazapine; • Cognitive impairment; • Behavioral therapy, problem-solving therapy, • Falls; interpersonal psychotherapy (27,32). Nortriptyline • Orthostatic hypotension; • Exacerbation of urinary symptom; • Prolongation of the QT interval; • Sudden cardiac death; • Urinary retention (27,32). • Anticholinergic and extrapyramidal effects (tardive dyskinesia); • Atypical neuroleptic drugs with a favorable risk/benefit • Parkinsonism; profile, for example, risperidone, melperone, pipamperon; • Hypotonia; • Clinical monitoring of adverse reactions, particularly • Sedation; anticholinergic and extrapyramidal, history of falls, • Stroke; neurological and cognitive function (e.g., parkinsonism); Olanzapine • Falls; • Monitor of cardiovascular function (hypotension, ECG / • Increased mortality in patients with dementia (2,6,7,31,32,34). QT interval); • Haloperidol can be used in higher doses for less than 3 days; • Butyrophenones (e.g., haloperidol) are contraindicated for Parkinson's disease;
• Olanzapine and quetiapine are contraindicated for diabetes; • Avoid antipsychotics for behavioral problems of dementia or delirium, unless non-pharmacological options (for example, behavioral interventions) have failed or are not possible and the elderly person is threatening substantial harm to himself or others (2,6,7,31,32). • Falls due muscle relaxing effect and possible hip fracture; • Valerian; • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • BZD (short or intermediate half-life); psychosis); • Drugs z: zolpidem, zopiclone, low dose zaleplon; • Depression; • Opipramol; • Cognitive impairment; • Sedative antidepressants (e.g. mirtazapine); • Delirium; Oxazepam • Low-potency neuroleptics (e.g. melperone, pipamperon); • Fractures (1,2,26,27,32). • Clinical monitoring of adverse reactions (cognitive function, surveillance, regular history of falls, gait firmness test, psychopathology, ataxia); • Avoid, if necessary, using the lowest dose for a short period (1,2,26,27).
• Cognitive impairment; • Avoid, if necessary, using the lowest dose for a short Oxazolam • Confusion; period (6). • Falls and fractures (6). • Anticholinergic effects (e.g., constipation, dry mouth); • Trospio; • Cognitive impairment; • Non-pharmacological treatment (pelvic floor exercises, • Urinary retention; physical and behavioral therapy); • Delirium; • Clinical monitoring of anticholinergic effects, central • Prolongation of the QT interval (26,31,32). nervous function and ECG; • Another muscarinic receptor antagonist is preferable; Oxybutynin • Non-pharmacological treatment (pelvic exercises, physical and behavioral therapy); • Other drug with less antimuscarinic activity at the level of the central nervous system; • If there is benign prostatic hypertrophy, use with a α1 receptor blocker. When necessary, combine with a laxative (26,31,32). • Stroke in people with dementia; • Avoid antipsychotics for behavioral problems of dementia Paliperidone • Cognitive impairment in people with dementia; or delirium, unless non-pharmacological options (for
• Mortality in people with dementia (6). example, behavioral interventions) have failed or are not possible and the elderly person is threatening substantial harm to himself or others (6). • Respiratory depression; • BZD (short or intermediate half-life) (32). • Cognitive impairment; Pentobarbital • Psychiatric reactions (agitation, irritability, hallucinations, psychosis); • Falls and fractures (32). • Ineffective treatment for dementia; • NR Pentoxifylline • Moderate risk of adverse reactions (33). • Anticholinergic and extrapyramidal effects (tardive dyskinesia); • Risperidone; • Parkinsonism; • Melperone; • Hypotonia; • Pipamperone; Perfenazine • Sedation; • Clinical monitoring for adverse reactions, particularly • Stroke; anticholinergic and extrapyramidal, history of falls, • Falls; neurological and cognitive function (e.g., parkinsonism); • Increased mortality in patients with dementia (26,32). • Monitor of cardiovascular function (hypotension, ECG/QT interval) (26,32). • Anticholinergic and extrapyramidal effects; • Non-phenothiazine neuroleptics with less anticholinergic activity (clozapine, risperidone, olanzapine, amisulpride, Periciazine • Stroke in people with dementia (32). quetiapine); • Meprobamate (32). • Extrapyramidal effects; • Decrease the use of typical antipsychotic medications; • Super sedation; • Butyrophenones (e.g., haloperidol) are contraindicated for Perospirone • Cognitive impairment; Parkinson's disease; • Cerebrovascular disorders; • Olanzapine and quetiapine are contraindicated for diabetes • Mortality (31). (31). • Cognitive impairment; • Other antiepileptic drugs (e.g. lamotrigine, valproic acid, • Sedation; levetiracetam, gabapentin); • Drowsiness; • Clinical monitoring of adverse reactions (gait stability test, • Impaired memory; coordination; psychopathology); Phenobarbital • Paradoxical reaction; • Therapeutic drug monitoring (32). • Irritability; • Dyskinesia; • Ataxia; • Respiratory depression (32,34). Phenytoin • Central nervous system depression; • Start treatment at low doses;
• Delirium; • Monitor plasma concentration to adjust the dose (32). • Ataxia; • Tremors; • Anemia; • Osteomalacia; • Falls (32,36). • Anticholinergic and extrapyramidal effects; • Atypical antipsychotics with less anticholinergic effects, Pimozide • Delirium; for example, risperidone (32). • Stroke in people with dementia (25,32). • Anticholinergic and extrapyramidal effects; • Non-phenothiazine neuroleptics with less anticholinergic • Delirium; activity (clozapine, risperidone, olanzapine, amisulpride, Pipothiazine • Stroke in people with dementia (32). quetiapine); • Meprobamate (32). • Orthostatic hypotension; • Reduce the dose in cases of moderate to severe kidney • Symptoms of the gastrointestinal tract; failure; • Hallucinations; • Start with 3 doses of 0.125 mg per day, gradually increase Pramipexole • Confusion; to 1.5 to 4.5 mg per day (14). • Insomnia; • Peripheral edema (14). • Falls due muscle relaxing effect and possible hip fracture; • BZD (short or intermediate half-life); • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Drugs z: zolpidem, zopiclone, low dose zaleplon; psychosis); • Opipramol; • Depression; • Sedative antidepressants (e.g. mirtazapine); • Cognitive impairment; Prazepam • Low-potency neuroleptics (e.g. melperone, pipamperon); • Delirium; • Clinical monitoring of adverse reactions (cognitive • Fractures (6,26). function, surveillance, regular history of falls, gait firmness test, psychopathology, ataxia); • Avoid, if necessary, using the lowest dose for a short period (6,26). • Increased mortality in patients with dementia (27). • Neuroleptics with better risk / benefit ratio, for example risperidone, pipamperon, haloperidol (in acute psychosis, short-term use less than 3 days); Prochlorperazine • Non-pharmacological interventions for delirium, multicomponent intervention); • Identification of clinical changes during the prodromal phase;
• Psychological strategies adapted to patients: music, reminiscence therapy, exposure to pets, outdoor activities, exposure to bright light; • In agitation and aggression, try to identify the cause of the problem; it can be illness, pain, medication (27); • Anticholinergic effect (constipation, dry mouth, visual disturbance, • Second generation antihistamines (e.g., cetirizine, bladder dysfunction, confusion, sedation, cognitive impairment); loratadine, desloratadine); • Prolongation of the QT interval; • Discontinue treatment 1 day before surgery (32,36) Prometazine • Ventricular arrhythmia; • Delirium; • Sudden cardiac death (27,32,36). • Dry mouth; • If there is benign prostatic hypertrophy, use with an α1 • Constipation; receptor blocker; Propiverine • Exacerbation of urinary symptoms; • When necessary, combine with a laxative (31). • Urinary retention; • Cognitive impairment (31). • Develop osteoporosis / fracture; • NR Proton pump • Dementia; inhibitor • Kidney failure with prolonged use (9). • Cognitive impairment; • NR Quazepam • Delirium; • Falls and fractures (5). • Extrapyramidal effects; • Decrease the use of typical antipsychotic medications; • Super sedation; • Use when absolutely necessary. Butyrophenones (e.g., Quetiapine • Cognitive impairment; haloperidol) are contraindicated for Parkinson's disease; • Cerebrovascular disorders; • Olanzapine and quetiapine are contraindicated for diabetes • Stroke and mortality in dementia patients (7,31). (31). • Induce or aggravate the delusion (6,14,36). • Proton pump inhibitors, use should not be longer than 8 Ranitidine weeks (14). • Depression; • Other antihypertensive agents, for example, angiotensin- • Impotence; converting enzyme inhibitors, angiotensin receptor • Sedation; antagonists, thiazides, beta-blockers, calcium antagonists Reserpine • Orthostatic hypotension (1,26,37). (long-acting, with peripheral effect); • Monitor of cardiovascular function, central nervous effects, and other adverse reactions; (for example, impaired urination) (26).
• Orthostatic hypotension; • Other antihypertensive, except short-acting calcium • Bradycardia; channel blockers and centrally acting antihypertensive Rilmenidine • Syncope, effects on the central nervous system (sedation, depression, (14,32). cognitive impairment) (14,32). • Insomnia; • Use the lowest dose required (0.5 to 1.5 mg per day) for • Mild peripheral edema. the shortest period of time required; • Unfavorable risk / benefit in the treatment of behavioral symptoms of • For geriatric patients or in cases of severe renal failure dementia; (CrCl <30 mL / min), start with 0.5 mg twice a day; • Stroke and increased mortality in patients with dementia. increase doses by 0.5 mg twice a day; Increases above 1.5 • Extrapyramidal effects; mg twice daily should be done at intervals of at least 1 • Supersedation; week; • Cognitive impairment; • Decrease the use of typical antipsychotic drugs. Use when absolutely necessary; Risperidone • Cerebrovascular disorders (6,7,10,14,31,32). • Butyrophenones (e.g., haloperidol) are contraindicated for Parkinson's disease; • Olanzapine and quetiapine are contraindicated for diabetes; • Avoid antipsychotics for behavioral problems of dementia or delirium, unless non-pharmacological options (for example, behavioral interventions) have failed or are not possible and the elderly person is threatening substantial harm to himself or others (6,14,31,32). • Neuromuscular block; • Avoid new prescriptions during the perioperative period; Rivastigmine • Postoperative delirium (36). continue long-term medication with close monitoring (36). • Delirium; • NR Scopolamine • Cognitive impairment (36). • Anticholinergic effects (eg, constipation, dry mouth); • Trospio; • Cognitive impairment; • Non-pharmacological treatment (pelvic floor exercises, • Dry mouth; physical and behavioral therapy); • Clinical monitoring of side effects (anticholinergics); Solifenacin • Constipation; • Exacerbation of urinary symptoms; • Monitoring of central nervous function and ECG; • Urinary retention; • If there is benign prostatic hypertrophy, use with a α1 • Prolongation of the QT interval (26,31,35). receptor blocker. When necessary, combine with a laxative (26,31). • Cognitive impairment; • For anxiety: BZD (short or intermediate half-life), Temazepam • Delirium; mirtazapine, trazodone, mianserin. • Falls and fractures; • For hypnotic indication: zolpidem, zopiclone, valerian.
• Dependence; • Non-pharmacological interventions for anxiety: cognitive- • Cognitive impairment; behavioral therapy; • Delirium; • Non-pharmacological interventions for insomnia: sleep • Dizziness; hygiene, identify the cause of the sleep disorder; • Falls and fractures (1,7,26,27). • Try to decrease. If prescription is unavoidable, prescribe short-acting agents, such as alprazolam or lorazepam, for a short period (7,26,27) (1). • Atrial fibrillation; • Inhaled drugs, including tiotropium, glucocorticoids; • Tachycardia; • Long-acting beta-sympathomimetic drugs (34). • Cardiac arrhythmia; • Convulsions; Theophylline • Insomnia; • Irritability; • Vomiting; • Diarrhea (34). • Anticholinergic effects (drowsiness, confusion and cognitive • Atypical neuroleptics with a favorable risk / benefit impairment); profile, for example, risperidone, melperone, pipamperon. • Extrapyramidal effects (tardive dyskinesia); • Clinical monitoring of adverse reactions, particularly • Parkinsonism; anticholinergic and extrapyramidal reactions, history of Thioridazine • Hypotonia; fall, neurological and cognitive function (e.g., • Sedation; parkinsonism); • Stroke; • Monitor of cardiovascular function (hypotension, QT • Falls; interval and blood pressure); • Increased mortality in patients with dementia (26,32,34). • Discontinue (26,32). • Respiratory depression; • Non-pharmacological therapy; • Cognitive impairment; • Lower dosage of short half-life benzodiazepine (e.g., Tiopental • Psychiatric reactions (agitation, irritability, hallucinations, lorazepam, midazolam, alprazolam). psychosis); • Barbituric only in convulsive treatment (32). • Falls and fractures (32). • Anticholinergic effects (eg, constipation, dry mouth); • Trospio; • Cognitive impairment; • Non-pharmacological treatment (pelvic floor exercises, • Prolongation of the QT interval (26,31,32). physical and behavioral therapy); • Clinical monitoring of anticholinergic effects, central Tolterodine nervous function and ECG; • If there is benign prostatic hypertrophy, use with a α1 receptor blocker. When necessary, combine with a laxative;
• Avoid, if possible, or administer with electrocardiographic control and monitoring the effects on the CNS; • Do not use in patients with cognitive impairment or narrow-angle glaucoma (26,31,32). • Lowering the seizure threshold; • NR • Delirium; Torasemide • Vomiting; • Dizziness; • Constipation (32,34). • Epilepsy; • Use with caution (36). Tramadol • Delirium (36). • In the treatment for insomnia: cognitive and behavioral • Valerian; abnormalities; • BZD (short or intermediate half-life); • Falls due muscle relaxing effect and possible hip fracture; • Drugs z: zolpidem, zopiclone, low dose zaleplon; • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Opipramol; psychosis); • Sedative antidepressants (e.g. mirtazapine); • Depression; • Low-potency neuroleptics (e.g. melperone, pipamperon); • Cognitive impairment; • Clinical monitoring of adverse drug reactions (cognitive • Delirium; function, surveillance, regular history of falls, gait Triazolam • Fractures; firmness test, psychopathology, ataxia); • Dizziness (1,6,7,26,27,31,33). • Non-pharmacological therapy, minimum short-term dosage as needed • It should not be used for long periods. • Triazolam can induce amnesia, so its use is not recommended. If used, administer lower doses for as short a period as possible; • Avoid, if necessary to administer the lowest possible dose for a short period of time (1,6,7,26,27,31,33). • Anticholinergic adverse reactions (urinary retention, cognitive • SSRI; Tricyclic impairment, glaucoma, orthostatic hypotension, falls, arrhythmias antidepressants • SNRI (34). prolongation of the QT interval and dry mouth (34). • Extrapyramidal effects; • Levodopa with peripheral dopa decarboxylase inhibitors; • Supersedation; • Another dopaminergic agonist, except cabergoline (32). Triexiphenidyl • Cognitive impairment; • Cerebrovascular disorders; • Mortality (31,32).
• Adverse anticholinergic and extrapyramidal effects; • Neuroleptics with the best risk / benefit ratio, for example • Stroke and increased mortality in patients with dementia (27,32). risperidone, pipamperon, haloperidol (in acute psychosis, short-term use with less than 3 days). • Non-pharmacological interventions for delirium, multicomponent intervention); • Identification of clinical changes during the prodromal Trifluoperazine phase. • Psychological strategies adapted to patients: music, reminiscent therapy, exposure to pets, outdoor activities, exposure to bright light; • In agitation and aggression, try to identify the cause of the problem; it can be illness, pain, medication (27,32); • Peripheral anticholinergic effects (eg, constipation, dry mouth, • SSRI; orthostatic hypotension, cardiac arrhythmia), central anticholinergic • SNRI; effects (drowsiness, internal restlessness, confusion, other types of • Mirtazapine delirium); • Non-pharmacological treatments, such as behavioral • Cognitive impairment; therapy; Trimipramine • Falls (26,29). • Monitoring of anticholinergic effects, suicide; fall risk assessment; • ECG monitoring; • Therapeutic monitoring of drugs if there is a risk of intoxication (26,29). • Anticholinergic effects (e.g., constipation, dry mouth); • Second generation antihistamines (e.g., cetirizine, • Cognitive impairment; loratadine, desloratadine); Triprolidine • Prolongation of the QT interval (26). • Clinical monitoring of anticholinergic effects; • Monitor of central nervous function and ECG (26); • Falls due muscle relaxing effect and possible hip fracture; • BZD (short or intermediate half-life); • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Drugs z: zolpidem, zopiclone, low dose zaleplon; psychosis); • Opipramol; • Cognitive impairment; • Sedative antidepressants (e.g. mirtazapine); • Fractures (1,6,26,32,36). Zaleplom • Low-potency neuroleptics (e.g. melperone, pipamperon); • Clinical monitoring of adverse reactions (cognitive function, surveillance, regular history of falls, gait firmness test, psychopathology, ataxia); • Administer in low doses and for a short period of time (1,6,26,32,36).
• Anticholinergic and extrapyramidal effects; • Atypical antipsychotics with less anticholinergic effects • Stroke in people with dementia; (e.g. Risperidone) (32). • Prolongation of the QT interval; Ziprasidone • Ventricular arrhythmia; • Torsade de pointes; • Sudden cardiac death (32). • Falls due muscle relaxing effect and possible hip fracture; • Valerian; • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • BZD (short or intermediate half-life); psychosis); • Drugs Z: zolpidem, zopiclone, low dose zaleplon; • Cognitive impairment; • Opipramol; • Fractures (2,5,6,26,27,32,36). • Sedative antidepressants (e.g. mirtazapine); Zolpidem • Low-potency neuroleptics (e.g. melperone, pipamperon); • Clinical monitoring of adverse drug reactions (cognitive function, surveillance, regular history of falls, gait firmness test, psychopathology, ataxia); • Non-pharmacological therapy. • Use with caution or discontinue (2,5,6,26,27,32,36). • Falls due muscle relaxing effect and possible hip fracture; • Valerian; • Psychiatric reactions (e.g., agitation, irritability, hallucinations, • Short or intermediate half-life BZD; psychosis); • Drugs z: zolpidem, zopiclone, low dose zaleplon; • Cognitive impairment; • Opipramol; • Fractures (2,6,26,27,32,36). • Sedative antidepressants (e.g. mirtazapine); Zopiclone • Low-potency neuroleptics (e.g. melperone, pipamperon); • Clinical monitoring of adverse drug reactions (cognitive function, surveillance, regular history of falls, gait firmness test, psychopathology, ataxia); • Non-pharmacological therapy; • Use with caution or discontinue (2,6,26,27,32,36). Stroke n people with dementia; Avoid antipsychotics for behavioral problems of dementia or Cognitive impairment n people with dementia; delirium, unless non-pharmacological options (for example, Zotepine Mortality in people with dementia (6). behavioral interventions) have failed or are not possible and the elderly person is threatening substantial harm to himself or others (6).
References
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