Cardiovascular Toxicology

, Volume 10, Issue 4, pp 306–310

Potential Cardiotoxic Reaction Involving Rivastigmine and Beta-Blockers: A Case Report and Review of the Literature



We report a case of potential cardiovascular toxicity including syncope, bradycardia, and ECG pauses associated with the use of rivastigmine and atenolol. A 65-year-old African American female with a medical history of dementia, hypertension, seizure disorder, stroke, and peripheral vascular disease was admitted to the hospital with shortness of breath and syncope. She was witnessed to have experienced a presyncopal episode followed by a true syncopal episode in which she was unresponsive for 20–30 s. On day two of hospital stay, the patient’s ECG showed a sinus bradycardia with a heart rate in the 40 s and sinus pauses greater than 2 s in duration. Atenolol was immediately discontinued, with a continuance of the bradycardia despite one missed dose. The potentially toxic combination of rivastigmine and atenolol was then identified as a plausible causative factor of this patient’s syncope and was subsequently discontinued. This patient’s Naranjo adverse reaction probability score was five, which indicates a probable association between syncope and bradycardia with the combination of rivastigmine and atenolol [13]. Following the discontinuation of rivastigmine, the ECG pauses resolved and the patient’s heart rate returned to normal levels. The patient did not experience any further dizziness or syncope. A 65-year-old female developed syncope and subsequent ECG pauses with sinus bradycardia after being treated with rivastigmine for dementia. Atenolol may have further compounded this toxic effect by its pharmacodynamic mechanisms.


Atenolol Beta-blockers Bradycardia ECG pauses Rivastigmine Cholinesterase inhibitors Syncope Cardiovascular toxicity 


  1. 1.
    Masuda, Y. (2004). Cardiac effect of cholinesterase inhibitors used in Alzheimer’s disease-from basic research to bedside. Current Alzheimer Research, 1(4), 315–321.CrossRefPubMedGoogle Scholar
  2. 2.
    Rowland, J. P., Rigby, J., Harper, A. C., & Rowland, R. (2007). Cardiovascular monitoring with acetylcholinesterase inhibitors: A clinical protocol. Advances in Psychiatric Treatment, 13, 178–184.CrossRefGoogle Scholar
  3. 3.
    Morganroth, J., Graham, S., Hartman, R., & Anand, R. (2002). Electrocardiographic effects of rivastigmine. Journal of Clinical Pharmacology, 42, 558–568.CrossRefPubMedGoogle Scholar
  4. 4.
    Mini Mental State Exam (MMSE) accessed online August 15, 2008 and June 9, 2009 at
  5. 5.
    Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. (1996). The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology, 46, 1470.Google Scholar
  6. 6.
    Bradley, J. G., & Davis, K. A. (2003). Orthostatic hypotension. American Family Physician, 68, 2393–2398.PubMedGoogle Scholar
  7. 7.
    Corey-Bloom, J., Anand, R., Veach, J. for the ENA 713 B352 Study Group. (1998). Randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer’s disease. International Journal of Geriatric Psychopharmacology, 1, 55–65.Google Scholar
  8. 8.
    Rösler, M., Anand, R., Cicin-Sain, A., Gauthier, S., Agid, Y., Dal-Bianco, P., et al. on behalf of the B303 Exelon Study Group. (1998). Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: an international, randomized, controlled trial. British Medical Journal, 318, 633–640.Google Scholar
  9. 9.
    Schneider, L. S., Anand, R., Farlow, M. R. (1998) Systematic review of the efficacy of rivastigmine for patients with Alzheimer’s disease. International Journal of Geriatric Psychopharmacology, 1(Suppl.1), S26–S34.Google Scholar
  10. 10.
    Ballard, C., Lane, R., Barone, P., Ferrara, R., & Tekin, S. (2006). Cardiac safety of rivastigmine in Lewy body and Parkinson’s disease dementia. International Journal of Clinical Practice, 60(6), 639–645.CrossRefPubMedGoogle Scholar
  11. 11.
    Ferrari, R., Cucchini, F., Bolognesi, R., et al. (1994). How do calcium antagonists differ in clinical practice? Cardiovascular Drugs and Therapy, 8, 565–575.CrossRefPubMedGoogle Scholar
  12. 12.
    Piepho RW. Pharmacology of the calcium channel blockers. [Internet] 2004 August [cited 2010 Aug 6] .Available from:
  13. 13.
    Kaufmann, H., Nahm, K., Purohit, D., & Wolfe, D. (2004). Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies. Neurology, 63, 1093–1095.PubMedGoogle Scholar
  14. 14.
    MICROMEDEX [database online]. Philadelphia: Thompson, Co. Copyright © 1974–2008. Atenolol and rivastigmine. Accessed on 08/14/2008.
  15. 15.
    Naranjo, C. A., Busto, U., Sellers, E. M., Sandor, P., Ruiz, I., Roberts, E. A., et al. (1981). A method for estimating the probability of adverse drug reactions. Clinical Pharmacology and Therapeutics, 30, 239–245.CrossRefPubMedGoogle Scholar
  16. 16.
    Bordier, P., Garrigue, S., Lanusse, S., Margaine, J., Robert, F., Gencel, L., et al. (2006). Cardiovascular effects and risk of syncope related to donepezil in patients with Alzheimer’s disease. CNS Drugs, 20(5), 411–417.CrossRefPubMedGoogle Scholar
  17. 17.
    Bordier, P., Lanusse, S., Garrigue, S., Reynard, C., Robert, F., Gencel, L., et al. (2005). Causes of syncope in patients with Alzheimer’s disease treated with donepezil. Drugs and Aging, 22(8), 687–694.CrossRefPubMedGoogle Scholar
  18. 18.
    Bordier, P., Garrigue, S., Barold, S. S., Bressolles, N., Lanusse, S., & Clementy, J. (2003). Significance of syncope in patients with Alzheimer’s disease treated with cholinesterase inhibitors. Europace, 5, 429–431.CrossRefPubMedGoogle Scholar
  19. 19.
    Fisher, A. A., & Davis, M. W. (2008). Prolonged QT interval, syncope, and delirium with galantamine. Annals of Pharmacotherapy, 42, 278–283.CrossRefPubMedGoogle Scholar
  20. 20.
    Kayrak, M., Yazici, M., Ayhan, S., Koc, F., & Ulgen, M. (2008). Complete atrioventricular block associated with rivastigmine therapy. American Journal of Health-System Pharmacy, 65, 1051–1053.CrossRefPubMedGoogle Scholar
  21. 21.
    Gill, S. S., Anderson, G. M., Fischer, H. D., Bell, C. M., Li, P., Normand, S., et al. (2009). Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: A population-based cohort study. Archives of Internal Medicine, 169(9), 867–873.CrossRefPubMedGoogle Scholar
  22. 22.
    American Psychiatric Association. (APA). Practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. Arlington (VA): American Psychiatric Association (APA); 2007 Oct. Accessed on June 9, 2009 at

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Pharmacy Practice, Auburn University Harrison School of PharmacyAuburn UniversityAuburnUSA

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