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Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis

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Abstract

Background and Objective

Domperidone is a drug used globally for relieving nausea and vomiting and stimulating breast milk production. Several case reports and studies linked domperidone usage with major cardiovascular adverse events (cardiac arrhythmia and sudden cardiac death). However, multiple randomized controlled efficacy studies failed to detect such adverse events. Our objectives were to systematically review and meta-analyze the association between current domperidone exposure and cardiovascular adverse events.

Methods

The first author performed EMBASE, PubMed and Scopus searches to identify human studies assessing the association between current domperidone exposure and cardiac arrhythmia or sudden death. Thirteen related articles were identified and the first and second authors independently reviewed the articles. Six studies were included in the final analysis. Meta-analysis was performed with a random effect model using the inverse variance approach. Heterogeneity was evaluated using the Q statistic and I 2 test.

Results

Five case-control studies and one case-crossover study were included in this meta-analysis. Pooled risk estimates demonstrated that the current use of domperidone increased the risk of ventricular arrhythmia and sudden cardiac death (pooled adjusted odds ratio = 1.70; 95 % confidence interval 1.47–1.97; I 2 = 0 %). The I 2 test showed that the underlying population was homogeneous.

Conclusions

Evidence from this meta-analysis suggests that current domperidone use increases the risk of cardiac arrhythmia and sudden cardiac death by 70 %. Domperidone usage in older populations should be discouraged. Larger observational studies or randomized controlled trials are needed to confirm the findings of this analysis.

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Acknowledgments

Nattawut Leelakanok would like to acknowledge the support from The Royal Thai Government Scholarship. We thank Saket Girotra for his assistance. We also thank Xiaomei Gu for her help in developing search terms; Daniel Fife from Johnson & Johnson for his references list; Elizabeth Asztalos, Mathieu Pasquier, and Patrick Pun for providing useful information from their publications.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 115 South Grand Avenue, PHAR 201, Iowa City, IA, 52242-1112, USA

    Nattawut Leelakanok

  2. Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA

    Andrea Holcombe & Marin L. Schweizer

  3. Division of General Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Marin L. Schweizer

  4. Iowa City VA Health Care System, Iowa City, IA, USA

    Marin L. Schweizer

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  1. Nattawut Leelakanok
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Correspondence to Nattawut Leelakanok.

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Funding

There was no external source of funding. MLS receives salary support from a VA Health Services and Research Career Development Award (CDA 11-215).

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NL, AH and MLS have no conflicts of interest to declare.

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Leelakanok, N., Holcombe, A. & Schweizer, M.L. Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis. Clin Drug Investig 36, 97–107 (2016). https://doi.org/10.1007/s40261-015-0360-0

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