International Journal of Clinical Pharmacy

, Volume 39, Issue 5, pp 1128–1139 | Cite as

Prevalence and nature of potential drug–drug interactions among kidney transplant patients in a German intensive care unit

  • Julia AmkreutzEmail author
  • Alexander Koch
  • Lukas Buendgens
  • Anja Muehlfeld
  • Christian Trautwein
  • Albrecht Eisert
Research Article


Background Complex polypharmacotherapy makes kidney transplant patients vulnerable to drug-drug interactions (DDIs). Objective To study prevalence and nature of potential DDIs (pDDIs) in kidney transplant patients. Setting Internal medicine ICU, University Hospital RWTH Aachen. Method In this retrospective observational study, pDDIs were identified in the first week after transplant from 1999 to 2010. Patients aged at least 18 years with prescription of at least two drugs were included. Patients with incomplete data were excluded. Data was originally obtained from medical charts. Two Clinical Decision Support Systems (CDSSs) in German language, mediQ and Meona, were used for pDDI identification and severity rating. Main outcome measure PDDIs in each severity level of the CDSSs/100 patient days. Results A total of 252 patients with 37,577 prescriptions were analysed. We found 99 pDDIs from severity levels major/contraindicated in Meona and 299 pDDIs from severity levels clinically relevant/strong in mediQ per 100 patient days. Most important potential consequences of pDDIs in respective severity levels were changes in immunosuppressant drug and potassium levels, nephrotoxicity and cardiac adverse events. Conclusion This study found a high prevalence of pDDIs in the first week after kidney transplant. Medication should be checked for pDDIs to prevent ADEs. It is strongly advisable to closely monitor patients within the first week after transplant for clinical and laboratory parameters and if necessary, change therapy. Physician education on the basis of study findings, DDI check with Clinical Physician Order Entry System/CDSSs and integration of a clinical pharmacist into the ward team should be targeted.


Clinical decision support systems Drug–drug interactions Germany Intensive care Kidney transplantation Pharmacoepidemiology 



The authors thank Dr. Tobias Schaefer and Pia Galuschka for providing access to Meona as well as Prof. Ulrich Jaehde, Katharina Schmitz and Christin Amkreutz for comments that improved the manuscript.



Conflicts of interest



  1. 1.
  2. 2.
    Kasiske BL, Zeier MG, Craig JC, Ekberg H, Garvey CA, Green MD, et al. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9 Suppl 3:S1–155.Google Scholar
  3. 3.
    Manitpisitkul W, McCann E, Lee S, Weir MR. Drug interactions in transplant patients: what everyone should know. Curr Opin Nephrol Hypertens. 2009;18:404–11.CrossRefPubMedGoogle Scholar
  4. 4.
    Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA. 1995;274:29–34.CrossRefPubMedGoogle Scholar
  5. 5.
    Cruciol-Souza JM, Thomson JC. Prevalence of potential drug–drug interactions and its associated factors in a Brazilian teaching hospital. J Pharm Pharm Sci. 2006;9:427–33.PubMedGoogle Scholar
  6. 6.
    Mertz D, Battegay M, Marzolini C, Mayr M. Drug-drug interaction in a kidney transplant recipient receiving HIV salvage therapy and tacrolimus. Am J Kidney Dis. 2009;54:e1–4.CrossRefPubMedGoogle Scholar
  7. 7.
    Siddiqi N, Marfo K. Clinically significant drug–drug interaction between tacrolimus and phenobarbital: the price we pay. J Pharm Pract. 2010;23:585–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Agroudy AE, Refaie AF, Moussa OM, Ghoneim MA. Tuberculosis in Egyptian kidney transplant recipients: study of clinical course and outcome. J Nephrol. 2003;16:404–11.PubMedGoogle Scholar
  9. 9.
    Jones TE. The use of other drugs to allow a lower dosage of cyclosporin to be used. Therapeutic and pharmacoeconomic considerations. Clin Pharmacokinet. 1997;32:357–67.CrossRefPubMedGoogle Scholar
  10. 10.
    Abarca J, Malone DC, Armstrong EP, Grizzle AJ, Hansten PD, Van Bergen RC, et al. Concordance of severity ratings provided in four drug interaction compendia. J Am Pharm Assoc. 2004;44:136–41.CrossRefGoogle Scholar
  11. 11.
    Vitry AI. Comparative assessment of four drug interaction compendia. Br J Clin Pharmacol. 2007;63:709–14.CrossRefPubMedGoogle Scholar
  12. 12.
    Zorina OI, Haueis P, Greil W, Grohmann R, Kullak-Ublick GA, Russmann S. Comparative performance of two drug interaction screening programmes analysing a cross-sectional prescription dataset of 84,625 psychiatric inpatients. Drug Saf. 2013;36:247–58.CrossRefPubMedGoogle Scholar
  13. 13.
    Smith WD, Hatton RC, Fann AL, Baz MA, Kaplan B. Evaluation of drug interaction software to identify alerts for transplant medications. Ann Pharmacother. 2005;39:45–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Vonbach P, Dubied A, Krähenbühl S, Beer JH. Evaluation of frequently used drug interaction screening programs. Pharm World Sci. 2008;30:367–74.CrossRefPubMedGoogle Scholar
  15. 15.
    Reis AMM, Cassiani SHDB. Evaluation of three brands of drug interaction software for use in intensive care units. Pharm World Sci. 2010;32:822–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Saverno KR, Hines LE, Warholak TL, Grizzle AJ, Babits L, Clark C, et al. Ability of pharmacy clinical decision-support software to alert users about clinically important drug-drug interactions. J Am Med Inform Assoc. 2011;18:32–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Amkreutz J, Koch A, Buendgens L, Trautwein C, Eisert A. Clinical decision support systems differ in their ability to identify clinically relevant drug interactions of immunosuppressants in kidney transplant patients. J Clin Pharm Ther. 2017;42:276–85.CrossRefPubMedGoogle Scholar
  18. 18.
    Fung KW, Kapusnik-Uner J, Cunningham J, Higby-Baker S, Bodenreider O. Comparison of three commercial knowledge bases for detection of drug–drug interactions in clinical decision support. J Am Med Inform Assoc. 2017.Google Scholar
  19. 19.
    Ramos GV, Guaraldo L, Japiassú AM, Bozza FA. Comparison of two databases to detect potential drug-drug interactions between prescriptions of HIV/AIDS patients in critical care. J Clin Pharm Ther. 2015;40:63–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Scheife RT, Hines LE, Boyce RD, Chung SP, Momper JD, Sommer CD, et al. Consensus recommendations for systematic evaluation of drug–drug interaction evidence for clinical decision support. Drug Saf. 2015;38:197–206.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Payne TH, Hines LE, Chan RC, Hartman S, Kapusnik-Uner J, Russ AL, et al. Recommendations to improve the usability of drug–drug interaction clinical decision support alerts. J Am Med Inform Assoc. 2015;22:1243–50.CrossRefPubMedGoogle Scholar
  22. 22.
    Tilson H, Hines LE, McEvoy G, Weinstein DM, Hansten PD, Matuszewski K, et al. Recommendations for selecting drug–drug interactions for clinical decision support. Am J Health-Syst Pharm. 2016;73:576–85.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Polidori P, Di Giorgio C, Provenzani A. Incidence of potential drug interactions in a transplant centre setting and relevance of electronic alerts for clinical practice support. Inform Prim Care. 2012;20:257–62.PubMedGoogle Scholar
  24. 24.
    ISMETT [Internet]. Accessed 15 June 2017.
  25. 25.
    van Leeuwen RWF, Brundel DHS, Neef C, van Gelder T, Mathijssen RHJ, Burger DM, et al. Prevalence of potential drug–drug interactions in cancer patients treated with oral anticancer drugs. Br J Cancer. 2013;108:1071–8.Google Scholar
  26. 26.
    mediQ [Internet]. Accessed 15 June 2017.
  27. 27.
    Meona [Internet]. Accessed 15 June 2017.
  28. 28.
    WHOCC - ATC/DDD Index [Internet]. Available from: Accessed 15 June 2017.
  29. 29.
    Horn JR, Hansten PD, Chan L-N. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother. 2007;41:674–80.CrossRefPubMedGoogle Scholar
  30. 30.
    Köhler GI, Bode-Böger SM, Busse R, Hoopmann M, Welte T, Böger RH. Drug-drug interactions in medical patients: effects of in-hospital treatment and relation to multiple drug use. Int J Clin Pharmacol Ther. 2000;38:504–13.CrossRefPubMedGoogle Scholar
  31. 31.
    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
  32. 32.
    Aros CA, Ardiles LG, Schneider HO, Flores CA, Alruiz PA, Jerez VR, et al. No gender-associated differences of cyclosporine pharmacokinetics in stable renal transplant patients treated with diltiazem. Transpl Proc. 2005;37:3364–6.CrossRefGoogle Scholar
  33. 33.
    Anglicheau D, Flamant M, Schlageter MH, Martinez F, Cassinat B, Beaune P, et al. Pharmacokinetic interaction between corticosteroids and tacrolimus after renal transplantation. Nephrol Dial Transpl. 2003;18:2409–14.CrossRefGoogle Scholar
  34. 34.
    David-Neto E, Takaki KM, Agena F, Romano P, Sumita NM, Mendes ME, et al. Diminished mycophenolic acid exposure caused by omeprazole may be clinically relevant in the first week posttransplantation. Ther Drug Monit. 2012;34:331–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Kennedy MS, Deeg HJ, Siegel M, Crowley JJ, Storb R, Thomas ED. Acute renal toxicity with combined use of amphotericin B and cyclosporine after marrow transplantation. Transplantation. 1983;35:211–5.CrossRefPubMedGoogle Scholar
  36. 36.
    Fachinformation Ramipril Abz Tabletten [Internet]. Accessed 15 June 2017.
  37. 37.
    Fachinformation Metoprolol Abz 50 mg/100 mg Tabletten [Internet]. Accessed 15 June 2017.
  38. 38.
    Franz CC, Egger S, Born C, Rätz Bravo AE, Krähenbühl S. Potential drug-drug interactions and adverse drug reactions in patients with liver cirrhosis. Eur J Clin Pharmacol. 2012;68:179–88.CrossRefPubMedGoogle Scholar
  39. 39.
    Reimche L, Forster AJ, van Walraven C. Incidence and contributors to potential drug-drug interactions in hospitalized patients. J Clin Pharmacol. 2011;51:1043–50.CrossRefPubMedGoogle Scholar
  40. 40.
    Egger SS, Meier S, Leu C, Christen S, Gratwohl A, Krähenbühl S, et al. Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT. Bone Marrow Transplant. 2010;45:1197–203.CrossRefPubMedGoogle Scholar
  41. 41.
    Depont F, Vargas F, Dutronc H, Giauque E, Ragnaud J-M, Galpérine T, et al. Drug–drug interactions with systemic antifungals in clinical practice. Pharmacoepidemiol Drug Saf. 2007;16:1227–33.CrossRefPubMedGoogle Scholar
  42. 42.
    Yu DT, Peterson JF, Seger DL, Gerth WC, Bates DW. Frequency of potential azole drug–drug interactions and consequences of potential fluconazole drug interactions. Pharmacoepidemiol Drug Saf. 2005;14:755–67.CrossRefPubMedGoogle Scholar
  43. 43.
    Guastaldi RBF, Reis AMM, Figueras A, Secoli SR. Prevalence of potential drug–drug interactions in bone marrow transplant patients. Int J Clin Pharm. 2011;33:1002–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Julia Amkreutz
    • 1
    • 2
    Email author
  • Alexander Koch
    • 2
  • Lukas Buendgens
    • 2
  • Anja Muehlfeld
    • 3
  • Christian Trautwein
    • 2
  • Albrecht Eisert
    • 1
  1. 1.Hospital PharmacyUniversity Hospital RWTH AachenAachenGermany
  2. 2.Department of Medicine IIIUniversity Hospital RWTH AachenAachenGermany
  3. 3.Department of Medicine IIUniversity Hospital RWTH AachenAachenGermany

Personalised recommendations