International Journal of Clinical Pharmacy

, Volume 39, Issue 2, pp 343–353 | Cite as

Prevalence of drug interactions in elderly patients with multimorbidity in primary care

  • Susana Sánchez-FidalgoEmail author
  • Maria Isabel Guzmán-Ramos
  • Mercedes Galván-Banqueri
  • Máximo Bernabeu-Wittel
  • Bernardo Santos-Ramos
Review Article


Background Drug interactions (DIs) are a significant cause of medication-related problems. The aging population, high chronic diseases prevalence and polypharmacy are closely associated factors. Aim of the review To study the prevalence, types and associated factors of DIs in multimorbidity patients of over 65 years of age in primary care. Methods Relevant studies on DI prevalence in this population were reviewed in PubMed, Cochrane Library and EMBASE (January 2000–December 2015). Independent variables (duration, target population, age, sex, mean of drugs and diseases, geographical localization, DI databases used and study designs) and dependent variables (prevalence, number of DIs per 100 patients and per patient, number of clinically-relevant DIs per 100 patients, most common DI and associated factors) were classified for each article. Results The search generated 749 articles and 46 duplicates were discarded. After reviewing, 10 articles were included. Seven studies were observational and 3 were quasi-experimental. Seven out of 10 used interaction databases. Only 2 studies described both actual and potential DIs. The prevalence of multimorbidity patients with DI ranged from 25.1 to 100% and the number of DIs per 100 patients was from 30 to 388.3. All the lower values correspond to the study conducted at the nursing home. This could be due to special care offered in these centres, where the medication is more controlled. The most frequent DIs were reported in five articles. However, these results could not be correlated since they were ranked using different methodologies. ACEIs, diuretics and NSAID were the most common therapeutic groups. Finally, 5 studies identified factors associated with the presence of potential DIs. The number of drugs and age were the most significant factors. Conclusions There is little evidence of prevalence of actual and potential DIs in elderly patients with multimorbidity in outpatient settings, showing widely heterogeneous results.


Aged Drug interaction Outpatients Patients with multimorbidity Prevalence 




Conflicts of interest



  1. 1.
    Lenssen R, Heidenreich A, Schulz JB, Trautwein C, Fitzner C, Jaehde U, et al. Analysis of drug-related problems in three departments of a German University hospital. Int J Clin Pharm. 2016;38:119–26.CrossRefPubMedGoogle Scholar
  2. 2.
    Sharifi H, Hasanloei MA, Mahmoudi J. Polypharmacy-induced drug-drug interactions; threats to patient safety. Drug Res (Stuttg). 2014;64:633–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Parker MG, Thorslund M. Health trends in the elderly population: gettingbetter and getting worse. Gerontologist. 2007;47:150–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Boyd CM, Darer J, Boult C, Fried LP, Boult L, Wu AW. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. JAMA. 2005;294:716–24.CrossRefPubMedGoogle Scholar
  5. 5.
    Opondo D, Eslami S, Visscher S, de Rooij SE, Verheij R, Korevaar JC, et al. Inappropriateness of medication prescriptions to elderly patients in the primary care setting: a systematic review. PLoS ONE. 2012;7(8):e43617.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Panagioti M, Stokes J, Esmail A, Coventry P, Cheraghi-Sohi S, Alam R, Bower P. Multimorbidity and patient safety incidents in primary care: a systematic review and meta-analysis. PLoS ONE. 2015;10(8):e0135947.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    World Health Organisation. Definition of an older or elderly person. WHO, Geneva, Switzerland. 2010. Accessed 15 Aug 2016.
  8. 8.
    Orimo H, Ito H, Suzuki T, Araki A, Hosoi T, Sawabe M. Reviewing the definition of “elderly”. Geriatr Gerontol Int. 2006;6:149–58.CrossRefGoogle Scholar
  9. 9.
    Nabovati E, Vakili-Arki H, Taherzadeh Z, Hasibian MR, Abu-Hanna A, Eslami S. Drug-drug interactions in inpatient and outpatient settings in Iran: a systematic review of the literature. Daru. 2014;25(22):52.CrossRefGoogle Scholar
  10. 10.
    Doubova-Dubova SV, Reyes-Morales H, Torres-Arreola LP, Suárez-Ortega M. Potential drug drug and drug disease interactions in prescriptions for ambulatory patients over 50 years of age in family medicine clinics in Mexico City. BMC Health Serv Res. 2007;19(7):147.CrossRefGoogle Scholar
  11. 11.
    Liao HL, Chen JT, Ma TC, Chang YS. Analysis of drug-drug interactions (DDIs) in nursing home in Central Taiwan. Arch Gerontol Geriatr. 2008;47:99–107.CrossRefPubMedGoogle Scholar
  12. 12.
    Gagne JJ, Maio V, Rabinowitz C. Prevalence and predictors of potential drugdrug interactions in Regione EmiliaRomagna, Italy. J Clin Pharm Ther. 2008;33:14151.CrossRefGoogle Scholar
  13. 13.
    Tulner LR, Frankfort SV, Gijsen GJ, van Campen JP, Koks CH, Beijnen JH. Drug drug interactions in a geriatric outpatient cohort: prevalence and relevance. Drugs Aging. 2008;25:3435.CrossRefGoogle Scholar
  14. 14.
    Galindo-Ocaña J, Gil-Navarro MV, García-Morillo JS, Bernabeu-Wittel M, Ollero-Baturone M, Ortiz-Camuñez MA. Drug drug interactions in multicentre polypathological polymedicated patients. Rev Clin Esp. 2010;210:2708.Google Scholar
  15. 15.
    Fiss T, Dreier A, Meinke C, van den Berg N, Ritter CA, Hoffmann W. Detection of drug related problems in an interdisciplinary health care model for rural areas in Germany. Pharm World Sci. 2010;32:566–74.CrossRefPubMedGoogle Scholar
  16. 16.
    Hoffmann W, van den Berg N, Thyrian JR, Fiss T. Frequency and determinants of potential drug drug interactions in an elderly population receiving regular home visits by Gps results of the home medication review in the AgnESstudies. Pharmacoepidemiol Drug Saf. 2011;20:13118.Google Scholar
  17. 17.
    Marusic S, BacicVrca V, Obreli Neto PR, Franic M, Erdeljic V, GojoTomic N. Actual drugdrug interactions in elderly patients discharged from internal medicine clinic: a prospective observational study. Eur J Clin Pharmacol. 2013;69:171724.CrossRefGoogle Scholar
  18. 18.
    Fiß T, MeinkeFranze C, van den Berg N. Hoffmann W Effects of a three party healthcare network on the incidence levels of drug related problems. Int J Clin Pharm. 2013;35:76371.CrossRefGoogle Scholar
  19. 19.
    Bazargan M, Yazdanshenas H, Han S, Orum G. Inappropriate medication use among underserved elderly African Americans. J Aging Health. 2016;28:118–38.CrossRefPubMedGoogle Scholar
  20. 20.
    Malone DC, Abarca J, Hansten PD, Grizzle AJ, Armstrong EP, Van Bergen RC, Duncan-Edgar BS, Solomon SL, Lipton RB. Identification of serious drug–drug interactions: results of the partnership to prevent drug–drug interactions. J Am Pharm Assoc. 2004;44:142–51.CrossRefGoogle Scholar
  21. 21.
    Samsa GP, Hanlon JT, Schmader KE. A summated score for theMedication Appropriateness Index: development and assessment of clinimetric properties including content validity. J Clin Epidemiol. 1994;47:891–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Charlson ME, Pompei P, Ales KA, Mackenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies. J Chron Dis. 1987;40:373–83.CrossRefPubMedGoogle Scholar
  23. 23.
    Maio V, Yuen EJ, Novielli K, Smith KD, Louis DZ. Potentially inappropriate medication prescribing for elderly outpatients in Emilia Romagna, Italy: a population-based cohort study. Drugs Aging. 2006;23:915–24.CrossRefPubMedGoogle Scholar
  24. 24.
    Clark DO, Von Korff M, Saunders K, Baluch WM, Simon GE. A chronic disease score with empirically derived weights. Med Care. 1995;33:783–95.CrossRefPubMedGoogle Scholar
  25. 25.
    Mallet L, Spinewine A, Huang A. The challenge of managing drug interactions in elderly people. Lancet. 2007;370:185–91.CrossRefPubMedGoogle Scholar
  26. 26.
    Dechamont S, Maphanta S, Butthum B, Kongkew C. Hospital admissions/visits associated with drug-drug interactions: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf. 2014;23:489–97.CrossRefGoogle Scholar
  27. 27.
    Björkman IK, Fastbom J, Schmidt IK, Bernsten CB, the Pharmaceutical Care of the Elderly in Europe Research (PEER) Group. Drug–drug interactions in the elderly. Ann Pharmacother. 2002;36:1675–81.CrossRefPubMedGoogle Scholar
  28. 28.
    Abarca J, Malone DC, Armstrong EP, Grizzle AJ, Hansten PD, Van Bergen RC, Lipton RB. Concordance of severity ratings provided in four drug interaction compendia. J Am Pharm Assoc. 2003;2004(44):136–41.Google Scholar
  29. 29.
    Rodríguez-Terol A, Caraballo MO, Palma D, Santos-Ramos B, Molina T, Desongles T, et al. Quality of interaction database management systems. Farm Hosp. 2009;33:134–46.CrossRefPubMedGoogle Scholar
  30. 30.
    Zhang Y, Baicker K, Newhouse JP. Geographic variation in the quality of prescribing. N Engl J Med. 2010;363:1985–8.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Cusack BJ. Pharmacokinetics in older persons. Am J Geriatr Pharmacother. 2004;2:274–302.CrossRefPubMedGoogle Scholar
  32. 32.
    Perazella MA, Mahnensmith RL. Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis. J Gen Intern Med. 1997;12:646–56.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Uijtendaal EV, Zwart-van Rijkom JE, van Solinge WW, Egberts TC. Frequency of laboratory measurement and hyperkalaemia in hospitalised patients using serum potassium; oncentration increasing drugs. Eur J Clin Pharmacol. 2011;67:933–40.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Zwart-van Rijkom JE, Uijtendaal EV, ten Berg MJ, van Solinge WW, Egberts AC. Frequency and nature of drug–drug interactions in a Dutch university hospital. Br J Clin Pharmacol. 2009;68:187–93.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Cruciol-Souza JM, Thomson JC. Prevalence of potential drugdrug interactions and its associated factors in a Brazilian teaching hospital. Pharm Pharm Sci. 2006;9:427–33.Google Scholar
  36. 36.
    Janchawee B, Wongpoowarak W, Owatranporn T, Chongsuvivatwong V. Pharmacoepidemiologic study of potential drug interactions in outpatients of a university hospital in Thailand. J Clin Pharm Ther. 2005;30:13–20.CrossRefPubMedGoogle Scholar
  37. 37.
    Johnell K, Klarin I. The relationship between number of drugs and potential drug-drug interactions in the elderly. Drug Saf. 2007;30:911–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Viktil KK, Blix HS, Moger TA, Reikvam A. Polypharmacy as commonly defined is an indicator of limited value innthe assessment of drug-related problems. Br J Clin Pharmacol. 2007;63:187–95.CrossRefPubMedGoogle Scholar
  39. 39.
    Magro L, Moretti U, Leone R. Epidemiology and characteristics of adverse drug reactions caused by drug-drug interactions. Expert Opin Drug Saf. 2012;11:83–94.CrossRefPubMedGoogle Scholar
  40. 40.
    Steinman MA, Hanlon JT. Managing medications in clinically complex elders: “There’s got to be a happy medium”. JAMA. 2010;304:1592–601.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    National Institute for Health and Care Excellence (NICE). Multimorbidity: clinical assessment and management. London, United Kingdom, 2016. Accessed 15 Dec 2016.

Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  • Susana Sánchez-Fidalgo
    • 1
    Email author
  • Maria Isabel Guzmán-Ramos
    • 1
  • Mercedes Galván-Banqueri
    • 1
  • Máximo Bernabeu-Wittel
    • 2
  • Bernardo Santos-Ramos
    • 1
  1. 1.Pharmacy ServiceUniversity Hospital ValmeSevilleSpain
  2. 2.Internal Medicine ServiceUniversity Hospital Virgen del RocioSevilleSpain

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