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Prevalence of Potentially Severe Drug-Drug Interactions in Ambulatory Patients with Dyslipidaemia Receiving HMG-CoA Reductase Inhibitor Therapy

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Abstract

Background: Drug-drug interactions (DDIs) are a well known risk factor for adverse drug reactions. HMG-CoA reductase inhibitors (‘statins’) are a cornerstone in the treatment of dyslipidaemia and patients with dyslipidaemia are concomitantly treated with a variety of additional drugs. Since DDIs are associated with adverse reactions, we performed a cross-sectional study to assess the prevalence of potentially critical drug-drug and drug-statin interactions in an outpatient adult population with dyslipidaemia.

Methods: Data from patients with dyslipidaemia treated with a statin were collected from 242 practitioners from different parts of Switzerland. The medication list was screened for potentially harmful DDIs with statins or other drugs using an interactive electronic drug interaction program.

Results: We included 2742 ambulatory statin-treated patients (mean age ± SD 65.1 ± 11.1 years; 61.6% males) with (mean ± SD) 3.2 ± 1.6 diagnoses and 4.9 ± 2.4 drugs prescribed. Of those, 190 patients (6.9%) had a total of 198 potentially harmful drug-statin interactions. Interacting drugs were fibrates or nicotinic acid (9.5% of patients with drug-statin interactions), cytochrome P450 (CYP) 3A4 inhibitors (70.5%), digoxin (22.6%) or ciclosporin (cyclosporine) [1.6%]. The proportion of patients with a potential drug-statin interaction was 12.1% for simvastatin, 10.0% for atorvastatin, 3.8% for fluvastatin and 0.3% for pravastatin. Additionally, the program identified 393 potentially critical non-statin DDIs in 288 patients.

Conclusions: CYP3A4 inhibitors are the most frequent cause of potential drug interactions with statins. As the risk for developing rhabdomyolysis is increased in patients with drug-statin interactions, clinicians should be aware of the most frequently observed drug-statin interactions and how these interactions can be avoided.

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Acknowledgements

The present study was financially supported by Bristol-Myers Squibb, GmbH, Baar, Switzerland. Stephan Krähenbühl is supported by a grant from the Swiss National Science Foundation (3100-59812-03/1).

We thank the participating practitioners for their excellent cooperation. Special thanks are dedicated to Martin Asper, who died during this project and Claudius Gmiir for their excellent work within data managing.

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Authors and Affiliations

  1. Division of Clinical Pharmacology & Toxicology, University Hospital, Hebelstrasse 2, Basel, 4031, Switzerland

    Alexandra E. Rätz Bravo, Lydia Tchambaz, Raymond G. Schlienger &  Stephan Krähenbühl

  2. Hospital Pharmacy, Hospital Emmental, Burgdorf, Switzerland

    Anita Krähenbühl-Melcher

  3. Brunner and Hess Software AG, Zürich, Switzerland

    Lorenzo Hess

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  1. Alexandra E. Rätz Bravo
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  2. Lydia Tchambaz
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  6. Stephan Krähenbühl
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Correspondence to Stephan Krähenbühl.

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Rätz Bravo, A.E., Tchambaz, L., Krähenbühl-Melcher, A. et al. Prevalence of Potentially Severe Drug-Drug Interactions in Ambulatory Patients with Dyslipidaemia Receiving HMG-CoA Reductase Inhibitor Therapy. Drug-Safety 28, 263–275 (2005). https://doi.org/10.2165/00002018-200528030-00007

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