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Pharmacodynamic and pharmacokinetic drug interactions reported to VigiBase, the WHO global individual case safety report database

  • Pharmacoepidemiology and Prescription
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Abstract

Objective

Drug interactions resulting in adverse drug reactions (ADRs) represent a major health problem both for individuals and the community. Despite this, limited information is reported in the literature on the drug interaction categories responsible for causing ADRs. In the study reported here, we investigated the drug combinations most frequently co-reported as interacting in the WHO Global Individual Case Safety Report (ICSR) database, VigiBase, and categorised these according to the drug interaction mechanism.

Methods

Reports in which drug combinations were co-reported as interacting in at least 20 reports in VigiBase during the past 20 years were included in the study. Each drug combination was reviewed in the literature to identify the mechanism of interaction and subsequently classified as pharmacodynamic and/or pharmacokinetic reaction. Report characteristics were also analysed.

Results

A total of 3766 case reports of drug interactions from 47 countries were identified. Of the 123 different drug combinations reported, 113 were described in the literature to interact. The mechanism of the drug interaction was categorised as pharmacodynamic (46 combinations; 41%), pharmacokinetic (28; 25%), a combination of both types (18; 16%) and unidentified (21; 19%). Pharmacodynamic drug interactions primarily concerned pharmacological additive effects, whereas enzyme inhibition was the most frequent pharmacokinetic interaction. The combinations reviewed primarily implicated drugs such as warfarin, heparin, carbamazepine and digoxin.

Conclusions

Drug interactions reported in globally collected ADR reports cover both pharmacodynamic, specifically additive pharmacological effects, and pharmacokinetic mechanisms primarily accredited to the inhibition of hepatic cytochrome P450 enzymes. These ADR reports often concern serious threats to patients’ safety and are particularly related to the use of high risk drugs such as warfarin and heparin.

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Acknowledgements

The authors are indebted to the National Centres that contributed data. The opinions and conclusions in this study are not necessarily those of the various centres, nor those of the WHO. We are grateful for the advice given in the preparation of this article by Dr Staffan Hägg, Department of Drug Research/Clinical Pharmacology, Linköping University, Linköping, Sweden.

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Authors and Affiliations

  1. Uppsala Monitoring Centre, WHO Collaborating Centre for International Drug Monitoring, Box 1051, 751 40, Uppsala, Sweden

    Johanna Strandell

  2. Department of Drug Research/Clinical Pharmacology, Linköping University, Linköping, Sweden

    Johanna Strandell

  3. Department of Pharmaceutical Biosciences, Bioactivation and Toxicity, Uppsala University, Uppsala, Sweden

    Stina Wahlin

Authors
  1. Johanna Strandell
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  2. Stina Wahlin
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Correspondence to Johanna Strandell.

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Strandell, J., Wahlin, S. Pharmacodynamic and pharmacokinetic drug interactions reported to VigiBase, the WHO global individual case safety report database. Eur J Clin Pharmacol 67, 633–641 (2011). https://doi.org/10.1007/s00228-010-0979-y

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  • DOI: https://doi.org/10.1007/s00228-010-0979-y

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