Skip to main content
SpringerLink
Log in

Drug-drug interactions and their harmful effects in hospitalised patients: a systematic review and meta-analysis

  • Review
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Drug-drug interactions (DDIs) are often avoidable and, if undetected, can lead to patient harm. This review aimed to determine the prevalence of potential DDIs (pDDIs), clinically relevant DDIs (DDIs that could lead to measurable patient harm, taking into account the patient’s individual clinical profile) and DDIs that resulted in actual patient harm during hospitalisation.

Method

Four databases were scanned for English papers published from 2000 to 2016. Papers that reported prevalence of DDIs in the outpatient setting, at admission or discharge, involving only specific drugs, or in specific disease populations or age groups were excluded.

Results

Twenty-seven papers met the inclusion criteria and were graded for quality using the Critical Appraisal Skills Programme (CASP) cohort study checklist. Ten papers were rated as ‘poor’, 14 as ‘fair’ and only three papers as ‘good’. Overall, the meta-analysis revealed that 33% of general patients and 67% of intensive care patients experienced a pDDI during their hospital stay. It was not possible to determine the prevalence of clinically relevant DDIs or DDIs that resulted in actual patient harm as data on these categories were limited. Of the very few studies that reported on harm, only a small proportion of DDIs were found to have resulted in actual patient harm.

Conclusions

Standardisation of DDI definitions and research methods are required to allow meaningful prevalence rates to be obtained and compared. Studies that go further than measuring pDDIs are critically needed to determine the impact of DDIs on patient safety.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Dechanont S et al (2014) Hospital admissions/visits associated with drug-drug interactions: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 23(5):489–497

    Article  PubMed  Google Scholar 

  2. Hines LE, Murphy JE (2011) Potentially harmful drug-drug interactions in the elderly: a review. Am J Geriatric Pharmacotherapy 9(6):364–377

    Article  CAS  Google Scholar 

  3. Peyriere H et al (2003) Adverse drug events associated with hospital admission. Ann Pharmacother 37(1):5–11

    Article  PubMed  Google Scholar 

  4. Reis AMM, Cassiani SHB (2011) Prevalence of potential drug interactions in patients in an intensive care unit of a university hospital in Brazil. Clinics 66(1):9–15

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wright A et al (2012) Preventability of adverse drug events involving multiple drugs using publicly available clinical decision support tools. Am J Health Syst Pharm 69(3):221–227

    Article  CAS  PubMed  Google Scholar 

  6. Hines LE et al (2011) Critical issues associated with drug-drug interactions: highlights of a multistakeholder conference. Am J Health Syst Pharm 68(10):941–946. https://doi.org/10.2146/ajhp100440

    Article  PubMed  Google Scholar 

  7. Espinosa-Bosch M et al (2012) Prevalence of drug interactions in hospital healthcare. Int J Clin Pharm 34(6):807–817

    Article  PubMed  Google Scholar 

  8. Moura CS, Acurcio FA, Belo NO (2009) Drug-drug interactions associated with length of stay and cost of hospitalization. J Pharm Pharm Sci 12(3):266–272

    Article  CAS  PubMed  Google Scholar 

  9. Shad MU, Marsh C, Preskorn SH (2001) The economic consequences of a drug-drug interaction. J Clin Psychopharmacol 21(1):119–120

    Article  CAS  PubMed  Google Scholar 

  10. Bucsa C et al (2013) How many potential drug-drug interactions cause adverse drug reactions in hospitalized patients? Eur J Intern Med 24(1):27–33

    Article  PubMed  Google Scholar 

  11. Moura C, Prado N, Acurcio F (2011) Potential drug-drug interactions associated with prolonged stays in the intensive care unit: a retrospective cohort study. Clin Drug Investig 31(5):309–316

    Article  CAS  PubMed  Google Scholar 

  12. Becker ML et al (2007) Hospitalisations and emergency department visits due to drug-drug interactions: a literature review. Pharmacoepidemiol Drug Saf 16(6):641–651

    Article  PubMed  Google Scholar 

  13. Abideen S, Vivekanandan K, Mishra P (2015) Assessment of prevalence of potential drug-drug interactions in medical intensive care unit of a tertiary care hospital in India. Asian J Pharmaceutical Clinical Res 8(1):125–130

    Google Scholar 

  14. Kumara Swamy RC et al (2014) Prevalence of polypharmacy and drug to drug interactions in a tertiary care teaching hospital. Int Res J Pharmacy 5(10):778–782

    Article  Google Scholar 

  15. Ogata K et al (2014) Polypharmacy in elderly cancer patients. Ann Oncol 25:v100

    Article  Google Scholar 

  16. Sancar M et al (2011) Identification potential drug-drug interaction in elderly patients receiving polypharmacy prescription. Int J Clin Pharm 33(2):407

    Google Scholar 

  17. Sharifi H, Hasanloei MAV, Mahmoudi J (2014) Polypharmacy-induced drug-drug interactions; threats to patient safety. Drug Res 64(12):633–637

    Article  CAS  Google Scholar 

  18. Sindhu MS, Kannan B (2013) Investigating the factors affecting drug-drug interactions. Int J Pharm Bio Sci 4(4):P467–P476

    Google Scholar 

  19. Lima RE, De Bortoli Cassiani SH (2009) Potential drug interactions in intensive care patients at a teaching hospital. Rev Lat Am Enfermagem 17(2):222–227

    Article  PubMed  Google Scholar 

  20. Lubinga SJ, Uwiduhaye E (2011) Potential drug-drug interactions on in-patient medication prescriptions at Mbarara Regional Referral Hospital (MRRH) in western Uganda: prevalence, clinical importance and associated factors. Afr Health Sci 11(3):499–507

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Radozevic N, Gantumur M, Vlahovic-Palcevski V (2008) Potentially inappropriate prescribing to hospitalised patients. Pharmacoepidemiol Drug Saf 17(7):733–737

    Article  Google Scholar 

  22. Reimche L, Forster AJ, van Walraven C (2011) Incidence and contributors to potential drug-drug interactions in hospitalized patients. J Clin Pharmacol 51(7):1043–1050

    Article  CAS  PubMed  Google Scholar 

  23. Bertsche T et al (2010) Prevention of adverse drug reactions in intensive care patients by personal intervention based on an electronic clinical decision support system. Intensive Care Med 36(4):665–672

    Article  PubMed  Google Scholar 

  24. Classen DC, Phansalkar S, Bates DW (2011) Critical drug-drug interactions for use in electronic health records systems with computerized physician order entry: review of leading approaches. J Patient Saf 7(2):61–65

    Article  PubMed  Google Scholar 

  25. Saxena K, Lung BR, Becker JR (2011) Improving patient safety by modifying provider ordering behavior using alerts (CDSS) in CPOE system. AMIA Annual Symposium Proceedings, 2011, p 1207–1216

  26. van der Sijs H et al (2006) Overriding of drug safety alerts in computerized physician order entry. J Am Med Inform Assoc 13(2):138–147

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bryant AD, Fletcher GS, Payne TH (2014) Drug interaction alert override rates in the Meaningful Use era: no evidence of progress. Appl Clin Inform 5(3):802–813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ko Y et al (2007) Practitioners’ views on computerized drug-drug interaction alerts in the VA system. J Am Med Inform Assoc 14(1):56–64

    Article  PubMed  PubMed Central  Google Scholar 

  29. Chiatti C et al (2012) The economic burden of inappropriate drug prescribing, lack of adherence and compliance, adverse drug events in older people a systematic review. Drug Saf 35(Suppl. 1):73–87

    Article  PubMed  Google Scholar 

  30. Gnjidic D, Johnell K (2013) Clinical implications from drug-drug and drug-disease interactions in older people. Clinical Experimental Pharmacol Physiol 40(5):320–325

    Article  CAS  Google Scholar 

  31. (CASP), C.A.S.P. CASP checklists. 2013 [cited 2017 10th January]; Available from: http://www.casp-uk.net/checklists

  32. Freeman MF, Tukey JW (1950) Transformations related to the angular and the square root. Ann Math Stat 21(4):607–611

    Article  Google Scholar 

  33. Knapp G, Hartung J (2003) Improved tests for a random effects meta-regression with a single covariate. Stat Med 22(17):2639–2710

    Article  Google Scholar 

  34. Higgins JPT, Thompson SG, Deeks JJ (2003) Measuring inconsistency in meta-analysis. BMJ 327(7414):557–560

    Article  PubMed  PubMed Central  Google Scholar 

  35. Egger M, Davey Smith G, Schneider M (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. R Development Core Team, R (2013) a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

    Google Scholar 

  37. Al-Hajje A et al (2012) Medication prescribing errors: data from seven Lebanese hospitals. Le Journal medical libanais. Lebanese Medical J 60(1):37–44

    Google Scholar 

  38. Amin A et al (2011) Review of prescriber approach towards rational drug practice in hospitalised patients. J Ayub Medical College, Abbottabad: JAMC 23(1):19–22

    Google Scholar 

  39. Blix HS et al (2004) The majority of hospitalised patients have drug-related problems: results from a prospective study in general hospitals. Eur J Clin Pharmacol 60(9):651–658

    Article  PubMed  Google Scholar 

  40. Ismail M et al (2013) Potential drug-drug interactions in internal medicine wards in hospital setting in Pakistan. Int J Clin Pharm 35(3):455–462

    Article  CAS  PubMed  Google Scholar 

  41. Kaliamurthy K et al (2015) Study of drug-drug interactions in general medicine department of a tertiary care hospital. J Appl Pharmaceutical Sci 5(12):122–124

    Article  Google Scholar 

  42. Oertle, M., Frequency and nature of drug-drug interactions in a Swiss primary and secondary acute care hospital. Swiss Medical Weekly, 2012. 142 (February) (no pagination) (w13522)

  43. Pote S, Tiwari P, D'Cruz S (2007) Medication prescribing errors in a public teaching hospital in India: a prospective study. Pharm Pract (Granada) 5(1):17–20

    Article  Google Scholar 

  44. Soherwardi S, Chogtu B, Faizal P (2012) Surveillance of the potential drug-drug interactions in the medicine department of a tertiary care hospital. J Clin Diagn Res 6(7 Suppl):1258–1261

    Google Scholar 

  45. Tigabu B, Daba D, Habte B (2014) Drug-related problems among medical ward patients in Jimma University specialized hospital, Southwest Ethiopia. J Res Pharmacy Practice 3(1):1–5

    Article  Google Scholar 

  46. van Doormaal JE et al (2010) Comparison of methods for identifying patients at risk of medication-related harm. Qual Saf Health Care 19(6):e26

    PubMed  Google Scholar 

  47. Vonbach P et al (2008) Prevalence of drug-drug interactions at hospital entry and during hospital stay of patients in internal medicine. European J Internal Med 19(6):413–420

    Article  Google Scholar 

  48. Vrca VB et al (2005) Prescribing medication errors in hospitalised patients: a prospective study. Acta Pharma 55(2):157–167

    CAS  Google Scholar 

  49. Zwart-Van Rijkom JEF et al (2009) Frequency and nature of drug-drug interactions in a Dutch university hospital. Br J Clin Pharmacol 68(2):187–193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Bista DB et al (2009) Pattern of potential drug-drug interactions in the intensive care unit of a teaching hospital in Nepal: a pilot study. J Clin Diagn Res 3(4):1713–1716

    Google Scholar 

  51. Cruciol-Souza JM, Ferreira-Filho OF, Obreli-Neto PR (2012) Prevalence of potential drug-drug interactions in an intensive care unit at a Brazilian hospital. Lat Am J Pharm 31(10):1469–1475

    Google Scholar 

  52. Rodrigues AT et al (2015) Clinical relevancy and risks of potential drug-drug interactions in intensive therapy. Saudi Pharmaceutical J 23(4):366–370

    Article  Google Scholar 

  53. Smithburger PL, Kane-Gill SL, Seybert AL (2012) Drug-drug interactions in the medical intensive care unit: an assessment of frequency, severity and the medications involved. Int J Pharmacy Practice 20(6):402–408

    Article  Google Scholar 

  54. Uijtendaal EV et al (2014) Analysis of potential drug-drug interactions in medical intensive care unit patients. Pharmacotherapy 34(3):213–219

    Article  CAS  PubMed  Google Scholar 

  55. IUGG. List of developing countries. 2015 [cited 2017 17 February 2017]; Available from: http://www.iugg2015prague.com/list-of-developing-countries.htm

  56. Ammenwerth E et al (2008) The effect of electronic prescribing on medication errors and adverse drug events: a systematic review. J Am Med Inform Assoc 15(5):585–600. https://doi.org/10.1197/jamia.M2667 Epub 2008 Jun 25

    Article  PubMed  PubMed Central  Google Scholar 

  57. Radley DC et al (2013) Reduction in medication errors in hospitals due to adoption of computerized provider order entry systems. J Am Med Inform Assoc 20(3):470–476. https://doi.org/10.1136/amiajnl-2012-001241

    Article  PubMed  PubMed Central  Google Scholar 

  58. Shamliyan TA et al (2008) Just what the doctor ordered. Review of the evidence of the impact of computerized physician order entry system on medication errors. Health Serv Res 43(1 Pt 1):32–53. https://doi.org/10.1111/j.1475-6773.2007.00751.x

    PubMed  PubMed Central  Google Scholar 

  59. Westbrook JI et al (2013) The safety of electronic prescribing: manifestations, mechanisms, and rates of system-related errors associated with two commercial systems in hospitals. J Am Med Inform Assoc 20(6):1159–1167

    Article  PubMed  PubMed Central  Google Scholar 

  60. Weingart SN et al (2003) Physicians’ decisions to override computerized drug alerts in primary care. Arch Intern Med 163(21):2625–2631

    Article  PubMed  Google Scholar 

  61. Lyell D, Coiera E (2017) Automation bias and verification complexity: a systematic review. J Am Med Inform Assoc 24(2):423–431. https://doi.org/10.1093/jamia/ocw105

    PubMed  Google Scholar 

  62. Vanham D et al (2017) Drug-drug interactions in the intensive care unit: do they really matter. J Crit Care 38:97–103. https://doi.org/10.1016/j.jcrc.2016.09.014

    Article  CAS  PubMed  Google Scholar 

  63. Alyamani NA, Hopf Y, Williams DJ (2009) Prescription quality in an acute medical ward. Pharmacoepidemiol Drug Saf 18(12):1158–1165

    Article  PubMed  Google Scholar 

Download references

Contributions of authors statement

WYZ was responsible for the conception of the work, data collection, data analysis and interpretation and drafting of the manuscript. LR was responsible for data collection, data analysis and interpretation and critical revision of the manuscript. LL was responsible for data analysis and interpretation. RD was responsible for conception of the work and critical revision of the manuscript. JW was responsible for conception of the work and critical revision of the manuscript. MB was responsible for conception of the work, data analysis and interpretation and critical revision of the manuscript.

Funding

This review was funded by the Australian National Health and Medical Research Council Program Grant no. 1054146.

Author information

Authors and Affiliations

  1. Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Faculty of Medicine and Health Sciences, Macquarie University, Level 6, 75 Talavera Road, Sydney, NSW 2109, Australia

    Wu Yi Zheng, L. C. Richardson, L. Li, J. I. Westbrook & M. T. Baysari

  2. Department of Clinical Pharmacology and Toxicology, St Vincent’s Hospital, Darlinghurst, Australia

    R. O. Day

  3. St Vincent’s Clinical School, UNSW, Darlinghurst, Australia

    R. O. Day & M. T. Baysari

Authors
  1. Wu Yi Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. C. Richardson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. O. Day
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. I. Westbrook
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. T. Baysari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wu Yi Zheng.

Ethics declarations

The authors declare that they have no conflicts of interest.

Electronic supplementary material

ESM 1

(DOCX 72 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, W.Y., Richardson, L.C., Li, L. et al. Drug-drug interactions and their harmful effects in hospitalised patients: a systematic review and meta-analysis. Eur J Clin Pharmacol 74, 15–27 (2018). https://doi.org/10.1007/s00228-017-2357-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-017-2357-5

Keywords

Search

Navigation