European Journal of Clinical Pharmacology

, Volume 73, Issue 7, pp 875–882 | Cite as

Comparative analysis of three drug–drug interaction screening systems against probable clinically relevant drug–drug interactions: a prospective cohort study

  • Neža Muhič
  • Ales Mrhar
  • Miran BrvarEmail author
Pharmacoepidemiology and Prescription



Drug–drug interaction (DDI) screening systems report potential DDIs. This study aimed to find the prevalence of probable DDI-related adverse drug reactions (ADRs) and compare the clinical usefulness of different DDI screening systems to prevent or warn against these ADRs.


A prospective cohort study was conducted in patients urgently admitted to medical departments. Potential DDIs were checked using Complete Drug Interaction®, Lexicomp® Online™, and Drug Interaction Checker®. The study team identified the patients with probable clinically relevant DDI-related ADRs on admission, the causality of which was assessed using the Drug Interaction Probability Scale (DIPS). Sensitivity, specificity, and positive and negative predictive values of screening systems to prevent or warn against probable DDI-related ADRs were evaluated.


Overall, 50 probable clinically relevant DDI-related ADRs were found in 37 out of 795 included patients taking at least two drugs, most common of them were bleeding, hyperkalemia, digitalis toxicity, and hypotension. Complete Drug Interaction showed the best sensitivity (0.76) for actual DDI-related ADRs, followed by Lexicomp Online (0.50), and Drug Interaction Checker (0.40). Complete Drug Interaction and Drug Interaction Checker had positive predictive values of 0.07; Lexicomp Online had 0.04. We found no difference in specificity and negative predictive values among these systems.


DDI screening systems differ significantly in their ability to detect probable clinically relevant DDI-related ADRs in terms of sensitivity and positive predictive value.


Actual drug–drug interactions Potential drug–drug interactions Adverse drug reactions Drug–drug interaction screening systems 


Authors’ contributions

AM and MB designed the study. NM, AM, and MB analyzed medical records. NM interviewed the patients and wrote the first draft, to which all authors provided their input. All authors contributed to the final version of the manuscript, provided full access to the data presented, and had final responsibility for the decision to submit the study for publication.

Compliance with ethical standards

Informed consent was obtained.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interests

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Slovenian National Medical Ethics Committee (no. 27/1/15).


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Faculty of PharmacyUniversity of LjubljanaLjubljanaSlovenia
  2. 2.Centre for Clinical Toxicology and Pharmacology, Division of Internal MedicineUniversity Medical Centre LjubljanaLjubljanaSlovenia
  3. 3.Institute of Pathophysiology, Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia

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