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Use of Clarithromycin and Adverse Cardiovascular Events among Older Patients Receiving Donepezil

A Population-Based, Nested Case-Control Study

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Abstract

Background: Donepezil is a commonly used drug in older people that due to its procholinergic effects can provoke bradycardia and neurocardiogenic syncope. Donepezil is metabolized by the cytochrome P450 isozyme 3A4 (CYP3A4). Clarithromycin is a potent inhibitor of CYP3A4, and patients taking both of these drugs may be at increased risk of cardiac adverse events.

Objective: The aim of this study was to evaluate the association between recent use of clarithromycin and adverse cardiovascular events in elderly patients receiving donepezil.

Methods: A population-based, nested case-control study using provincial healthcare databases was conducted. The base cohort was made up of persons 66 years of age or older who were prescribed donepezil and also were prescribed clarithromycin, erythromycin, azithromycin, cefuroxime, moxifloxacin or levofloxacin. Cases were those members of the base cohort hospitalized for bradycardia, syncope or complete atrioventricular block. For each case patient, five controls were matched according to age, sex and residence (community or long-term care).

Results: Between July 2002 and March 2010, 17712 patients continuously receiving donepezil were prescribed one of the antibacterials. In 1400 person-years of follow-up, 59 cases were identified. As compared with azithromycin, there was no statistically significant association between use of clarithromycin in donepezil users and subsequent adverse cardiovascular events (odds ratio 0.67; 95% CI 0.28, 1.63). There was no significant risk associated with exposure to either cefuroxime or respiratory quinolones.

Conclusions: The use of clarithromycin in elderly donepezil users did not significantly increase the risk of adverse cardiovascular outcomes. However, our study cannot rule out a possible small increase in risk. Although anti-bacterials can be beneficial, care should be taken in selecting antibacterials for use in older people receiving donepezil.

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Acknowledgements

This study was funded by an Interdisciplinary Capacity Enhancement Grant (HOA-80075) from the Canadian Institutes of Health Research (CIHR) Institute of Gender and Health and the CIHR Institute of Aging and by a Team Grant (OTG-88591) from the CIHR Institute of Nutrition, Metabolism and Diabetes. J.R.H. is supported by a CIHR Vanier Canada Graduate Scholarship.

This study was conducted at the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred.

All authors declare no conflicts of interest. The CIHR, ICES and MOHLTC had no role in the study design; the collection, analysis and interpretation of data; the writing of the report; or the decision to submit the paper for publication.

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Authors and Affiliations

  1. Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Janine R. Hutson & Paula A. Rochon

  2. Sunnybrook Health Sciences Centre, Institute for Clinical Evaluative Sciences, Toronto, ON, Canada

    Hadas D. Fischer, Xuesong Wang, Andrea Gruneir, Nick Daneman, Sudeep S. Gill, Paula A. Rochon & Geoffrey M. Anderson

  3. Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada

    Andrea Gruneir, Paula A. Rochon & Geoffrey M. Anderson

  4. Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada

    Andrea Gruneir, Paula A. Rochon & Geoffrey M. Anderson

  5. Department of Medicine, Queen’s University, Kingston, ON, Canada

    Sudeep S. Gill

Authors
  1. Janine R. Hutson
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  2. Hadas D. Fischer
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  3. Xuesong Wang
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  4. Andrea Gruneir
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  5. Nick Daneman
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  6. Sudeep S. Gill
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  7. Paula A. Rochon
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  8. Geoffrey M. Anderson
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Correspondence to Janine R. Hutson.

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Hutson, J.R., Fischer, H.D., Wang, X. et al. Use of Clarithromycin and Adverse Cardiovascular Events among Older Patients Receiving Donepezil. Drugs Aging 29, 205–211 (2012). https://doi.org/10.2165/11599090-000000000-00000

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  • DOI: https://doi.org/10.2165/11599090-000000000-00000

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