European Journal of Clinical Pharmacology

, Volume 75, Issue 9, pp 1237–1248 | Cite as

Herb-drug interactions: a novel algorithm-assisted information system for pharmacokinetic drug interactions with herbal supplements in cancer treatment

  • Janine Ziemann
  • Annette Lendeckel
  • Susann Müller
  • Markus Horneber
  • Christoph A. RitterEmail author
Pharmacokinetics and Disposition



To develop a system to estimate the risk of herb-drug interactions that includes the available evidence from clinical and laboratory studies, transparently delineates the algorithm for the risk estimation, could be used in practice settings and allows for adaptation and update.


We systematically searched Drugbank, Transformer, Drug Information Handbook, European and German Pharmacopoeia and MEDLINE for studies on herb-drug interactions of five common medicinal plants (coneflower, ginseng, milk thistle, mistletoe and St. John’s wort). A diverse set of data were independently extracted by two researchers and subsequently analysed by a newly developed algorithm. Results are displayed in the form of interaction risk categories. The development of the algorithm was guided by an expert panel consensus process.


From 882 publications retrieved by the search, 154 studies were eligible and provided 529 data sets on herbal interactions. The developed algorithm prioritises results from clinical trials over case reports over in vitro investigations and considers type of study, consistency of study results and study outcome for clinical trials as well as identification, permeability, bioavailability, and interaction potency of an identified herbal perpetrator for in vitro investigations. Risk categories were assigned to and dynamically visualised in a colour-coded matrix format.


The novel algorithm allows to transparently generate and dynamically display herb-drug interaction risks based on the available evidence from clinical and laboratory pharmacologic studies. It provides health professionals with readily available and easy updatable information about the risk of pharmacokinetic interactions between herbs and oncologic drugs.


Herb-drug interactions Complementary medicine Herbal supplements Anticancer drugs Assessment algorithm 



Complementary and alternative medicine


Cytochrome P450


Uridine-diphosphate glucuronosyl transferase




Multidrug resistance



This work is part of the collaborative research project ‘Competence Network of Complementary Medicine in Oncology’ (Kompetenznetz Komplementärmedizin in der Onkologie - KOKON), which was funded by the Stiftung Deutsche Krebshilfe, Bonn, Germany (Project No. 110150). The authors also thank the following experts for helpful discussions while developing the algorithm and matrix: Joachim Boos, Thomas Efferth, Robert Herrmann, Wolfgang Kämmerer, Ulrich Klotz, Ulrike Lindequist, Klaus Mross, Friedemann Nauck, Friederich Overkamp and Oliver von Richter. In addition, we acknowledge the participation of the following pharmacy students in the independent data extraction and grading process: Kathleen Gewiese, Sophie Müller, Franziska Splettstößer and Anne Stolzenburg. Peter Kößler and Jan Less are acknowledged for their contributions in developing the database and programming the algorithm. Finally, Laura Russell edited the manuscript for English language.

Author contributions

AL and JZ searched the literature, extracted and assessed study data, developed the algorithm and participated in writing the manuscript. SM assessed study data and participated in writing the manuscript. MH participated in designing the research, developing the algorithm and writing the manuscript. CAR designed research, participated in developing the algorithm and wrote the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Pharmacy, Institute of PharmacyErnst-Moritz-Arndt-University of GreifswaldGreifswaldGermany
  2. 2.Department of Internal Medicine, Division of Oncology/Hematology and PneumologyParacelsus Medical University, Klinikum NuernbergNuernbergGermany

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