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Factors Associated with Serious Adverse Reactions to Cholinesterase Inhibitors

A Study of Spontaneous Reporting

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Abstract

Background: Cholinesterase inhibitors are used in Alzheimer’s disease, mostly in elderly persons with co-morbidities and receiving co-medications that could increase the risk of serious adverse reactions.

Objective: To identify factors associated with serious adverse drug reactions (ADRs) in patients treated with cholinesterase inhibitors.

Methods: All ADRs associated with donepezil, rivastigmine or galantamine were identified in the French pharmacovigilance database, from the launching of these drugs to January 2007. Serious ADRs (SADRs) were those that led to death, hospitalization or prolongation of hospitalization, or that were life threatening. A multiple logistic regression analysis was used to identify factors associated with seriousness in the reported adverse reactions.

Results: We identified 773 reports of ADRs related to cholinesterase inhibitor use, among which 438 (57%) concerned SADRs. The median age of patients was 80 years (interquartile range: 75–84 years); 65.1% were women. The most represented ADRs were those responsible for CNS disorders (17.0%), gastrointestinal disorders (16.2%) and cardiac rhythm disorders (11.2%). Factors associated with an increased risk of SADRs were: age (odds ratio [OR] 1.92; 95% CI 1.22, 3.02 for subjects aged 85 years and over), use of atypical antipsychotics (OR 2.15; 95% CI 1.04, 4.46), use of conventional antipsychotics (OR 2.06, 95% CI 1.10, 3.85), use of antihypertensive drugs (OR 2.11; 95% CI 1.47, 3.02) and use of drugs targeting the alimentary tract and metabolism (OR 1.62; 95% CI 1.06, 2.46). The use of benzodiazepines (long-acting or others), antidepressants (tricyclic or others) or antiarrhythmic drugs was not associated with the reporting of SADRs.

Conclusions: An increased risk of SADRs related to cholinesterase inhibitors was associated with the use of antipsychotics (with no difference between conventional and atypical antipsychotics), drugs targeting the alimentary tract/metabolism and antihypertensive drugs. It was not associated with the use of other psychotropic drugs, other non-psychotropic CNS drugs or with the use of antiarrhythmic agents. The association with drugs targeting the alimentary tract and metabolism could result from a protopathic bias or reflect the particular sensitivity to serious nausea and vomiting in patients already treated for gastrointestinal disorders. These results confirm that attention needs to be paid to patients receiving both cholinesterase inhibitors and antipsychotics.

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Acknowledgements

The authors would like to thank all members of the 31 French pharmacovigilance centres as well as the Agence Française de Sécurité Sanitaire des Produits de Santé (Afssaps) for the availability of the data. They also wish to thank Philip Robinson for his help in manuscript preparation. No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Service de Pharmacologie, INSERM U657, BP 36, Université Victor Segalen Bordeaux 2, F-33076, Bordeaux, France

    Antoine Pariente, Ghada Miremont-Salamé, Nicholas Moore & Annie Fourrier-Réglat

  2. CHU de Bordeaux, Bordeaux, France

    Antoine Pariente, Dina Joseph-Reinette Sanctussy, Ghada Miremont-Salamé, Nicholas Moore, Françoise Haramburu & Annie Fourrier-Réglat

  3. Department of Pharmacology, Université Victor Segalen, Bordeaux, France

    Antoine Pariente, Nicholas Moore & Annie Fourrier-Réglat

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  1. Antoine Pariente
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  2. Dina Joseph-Reinette Sanctussy
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  3. Ghada Miremont-Salamé
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Correspondence to Antoine Pariente.

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Pariente, A., Sanctussy, D.JR., Miremont-Salamé, G. et al. Factors Associated with Serious Adverse Reactions to Cholinesterase Inhibitors. CNS Drugs 24, 55–63 (2010). https://doi.org/10.2165/11530300-000000000-00000

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