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Drug Interactions with Cholinesterase Inhibitors

An Analysis of the French Pharmacovigilance Database and a Comparison of Two National Drug Formularies (Vidal, British National Formulary)

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Abstract

Background: Cholinesterase inhibitors (ChEIs) could be involved in several drug-drug interactions (DDIs) because of their complex pharmacodynamic and/or pharmacokinetic properties.

Aim: To identify spontaneous reports in the French Pharmacovigilance Database containing DDIs with the three ChEIs marketed in France (donepezil, galantamine or rivastigmine) and to compare the informativity of two national drug references, the French national formulary (Vidal) and the British National Formulary (BNF), for their ability to identify ChEI-related DDIs.

Methods: Spontaneous reports submitted to the French Pharmacovigilance Database concerning donepezil, galantamine or rivastigmine were reviewed by two clinical pharmacologists from Toulouse Regional Pharmacovigilance Centre. Spontaneous reports containing DDIs were identified according to Vidal, BNF or their own judgement (and with use of the interaction supplement of the French independent drug information bulletin La Revue Prescrire). Then, the potential of DDIs to result in adverse drug reactions (ADRs) was evaluated. Finally, the presentations of the different ChEIs in the two references (Vidal, BNF) were compared for their DDI informativity.

Results: A total of 1058 spontaneous reports were identified that involved ChEIs in the French Pharmacovigilance Database up to 31 March 2006; of these 376 (35.5%) contained at least one DDI according to experts’ judgement. In total, 118 DDIs (31.4%) were the cause of ADRs. Most of the DDIs were due to pharmacodynamic interactions (247 cases, 65.7%). The most frequently encountered drugs involved in DDIs were bradycardic (205 cases, 54.5%) and anticholinergic (118 cases, 31.4%) drugs. DDIs were found in 309 spontaneous reports (29.2%) according to Vidal and in 127 (12.0%) according to BNF. In total, 88 ’serious’ ADRs were related to DDIs (including seven deaths, mainly due to cardiovascular ADRs). The most frequently observed ADRs due to DDIs were cardiovascular (67 cases, mainly bradycardia, atrioventricular block and arterial hypotension) and neurological (33 cases, mainly mental confusion). Comparison of the different presentations of summary of product characteristics (SPC) showed that Vidal was more informative than BNF for all the ChEIs, and that galantamine had the most complete data in the two references.

Conclusion: DDIs were present in more than one-third of spontaneous reports including ChEIs registered in the French Pharmacovigilance Database. Approximately, one-third of these DDIs were the cause of ADRs. The informativity of European drug dictionaries differs substantially and Vidal was found to be more informative than BNF for all the ChEIs.

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Notes

  1. 1The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Perry EK. The cholinergic hypothesis: ten years on. Br Med Bull 1986; 42: 63–9

    PubMed  CAS  Google Scholar 

  2. Feinberg M. The problems of anticholinergic adverse effects in older patients. Drugs Aging 1993; 3: 335–48

    Article  PubMed  CAS  Google Scholar 

  3. Moore AR, O’Keeffe ST. Drug-induced cognitive impairment in the elderly. Drugs Aging 1999; 15: 15–28

    Article  PubMed  CAS  Google Scholar 

  4. Goodman Gilman A, Hardman GJ. The pharmacological basis of therapeutics. In: Standaert DG, Young AB, editors. Treat-ment of central nervous system degenerative disorders. 10th ed. New York: McGraw-Hill, 2001: 560–2

    Google Scholar 

  5. Johnston MV. Cognitive disorders. In: Johnston MV, MacDon-ald RL, Young AB, editors. Principles of drug therapy in neurology. Philadelphia (PA): Davis, 1992: 226–67

    Google Scholar 

  6. Rogers SL, Friedhoff LT. Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: an interim analysis of the results of a US multicentre open label extension study. Eur Neuropsychopharmacol 1998; 8: 67–75

    Article  PubMed  CAS  Google Scholar 

  7. Sweetman CS. Martidale: the complete drug reference. 34th ed.

  8. Donepezil (aricept). In: Current problems in pharmacovigilance. Vol. 25. London: MHRA, CHM, 1999 Mar [online]. Available from URL: http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary=true&ssDocName=CON007467&ssTargetNodeId=368 [Accessed 2007 Oct 11]

  9. Alzheimer’s disease: beware of interactions with cholinesterase inhibitors. Prescrire Int 2006; 15: 103–6

  10. Defilippi JL, Crismon ML. Drug interactions with cholinesterase inhibitors. Drugs Aging 2003; 20: 437–44

    Article  PubMed  CAS  Google Scholar 

  11. Roe CM, Anderson MJ, Spivack B. Use of anticholinergic medications by older adults with dementia. J Am Geriatr Soc 2002; 50: 836–42

    Article  PubMed  Google Scholar 

  12. Lu CJ, Tune LE. Chronic exposure to anticholinergic medications adversely affects the course of Alzheimer disease. Am J Geriatr Psychiatry 2003; 11: 458–61

    PubMed  Google Scholar 

  13. Evans R, Ireland G, Morley JE, et al. Pharmacology and aging. In: Sanders AB, editor. Emergency care of the elder person. St Louis (MO): Beverly Cracom Publications, 1996: 29–41

    Google Scholar 

  14. Terrell KM, Heard K, Miller DK. Prescribing to older ED patients. Am J Emerg Med 2006; 24: 468–78

    Article  PubMed  Google Scholar 

  15. Resnick NM. Geriatric medicine. In: Fouci AS, Braunwald E, Isselbacher KJ, et al., editors. Harrison’s principles of internal medicine. Vol. 1. 14th ed. New York: McGraw-Hill Companies Inc., 1998: 37–46

    Google Scholar 

  16. Schwartz JB. Clinical pharmacology. In: Hazzard WR, Blass JP, Ettinger Jr WH, et al., editors. Principles of geriatric medicine and gerontology. 4th ed. New York: McGraw-Hill Companies Inc., 1999: 303–31

    Google Scholar 

  17. Oates JA, Wilkinson GR. Principles of drug therapy. In: Fouci AS, Braunwald E, Isselbacher KJ, et al., editors. Harrison’s principles of internal medicine. Vol. 1. 14th ed. New York: McGraw-Hil Companies Inc., 1998: 411–22

    Google Scholar 

  18. Wong FS, Rho JP. Drug dosing and life-threatening drug reactions in the critically ill patient. In: Yoshikawa TT, Norman DC, editors. Acute emergencies and critical care of the geriat-ric patient. New York: Marcel Dekker Inc., 2000: 31–47

    Google Scholar 

  19. Portail Insée. Recensement de la population, Mars 1999 [online]. Available from URL: http://www.recensement.insee.fr [Accessed 2006 27 Nov 27]

  20. Dictionnaire VIDAL. 82nd ed. Paris: O.V.P eds., 2006

  21. British National Formulary. 51st ed. London: Pharmaceutical Press, 2006

  22. Sauwer F. Regulatory perspectives at European level. In: Fracchia GN, ed. European medicines research: prospectives in pharmacotoxicology and pharmacovigilance. Amsterdam: IOS Press, 1994: 30–6

    Google Scholar 

  23. Spreux A, Baldin B, Chichmanian RM. The pharmacovigilance system in practice. Transfus Clin Biol 1999; 6: 254–9

    Article  PubMed  CAS  Google Scholar 

  24. Welsch M, Alt M, Richard MH, et al. The French pharmacovigi-lance system: structure and missions. Press Med 2000; 29: 102–6

    CAS  Google Scholar 

  25. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis and management. Lancet 2000; 356: 1255–9

    Article  PubMed  CAS  Google Scholar 

  26. Interactions medicamenteuses, comprendre et decider. Rev Prescrire 2006; 270 (Suppl.): 110–4

  27. Moore N, Noblet C, Kreft-Jais C, et al. La banque de cas du système français de Pharmacovigilance: quelques exemples d’exploitation. Thérapie 1995; 50: 557–62

    PubMed  CAS  Google Scholar 

  28. Gony M, Lapeyre-Mestre M, Montastruc JL. Risk of serious extrapyramidal symptoms in patients with Parkinson’s disease receiving antidepressant drugs: a pharmacoepidemiologic study comparing serotonin reuptake inhibitors and other antidepressant drugs. Clin Neuropharmacol 2003; 26: 142–5

    Article  PubMed  CAS  Google Scholar 

  29. Guitton E, Montastruc JL, Lapeyre-Mestre M. French network of pharmacovigilance centers: influence of HCV or HBV coinfection on adverse drug reactions to antiretroviral drugs in HIV patients. Eur J Clin Pharmacol 2006; 62: 243–9

    Article  PubMed  Google Scholar 

  30. Berthet S, Lapeyre-Mestre M, Montastruc JL. Prevalence of diabetes in France and drug use: study based on the French Pharmacovigilance Database [in French]. Thérapie. In press

  31. Ramaroson H, Helmer C, Barberger-Gateau P, et al. Prevalence de la déemence et de la maladie d’ Alzheimer chez les personnes de 75 ans et plus: donnees réactualisées de la cohorte PA-QUID. Rev Neurol 2003; 159: 405–11

    PubMed  CAS  Google Scholar 

  32. Magnier V, Flipon E, Godefroy O, et al. Traitement anticholinestérasique de la maladie d’Alzheimer en Picardie. Rev Neurol 2005; 161: 211–3

    Article  PubMed  CAS  Google Scholar 

  33. Remy N, Lapeyre-Mestre M, Bareille MP, et al. Drug interactions: a prospective pilot study in primary health care [in French]. Thérapie 2000; 55: 395–8

    PubMed  CAS  Google Scholar 

  34. Lechevallier-Michel N, Molimard M, Dartigues JF, et al. Drugs with anticholinergic properties and cognitive performance in the elderly: results from the PAQUID study. Br J Clin Pharmacol 2005: 59: 143–51

    Article  PubMed  Google Scholar 

  35. Doucet J, Kalimoutou S, Chédru C, et al. Are the prescriptions of anticholinergic drugs adapted to the associated diseases and/ or drugs in the Alzheimer’s dementia? [in French]. Thérapie 2006; 61: 23–7

    Article  PubMed  Google Scholar 

  36. Agence française de sécurité sanitaire des produits de santé« Réminyl○ (galantamine) et mortalite: résultats de deux essais cliniquesmenés chez des patients atteints d’une altération moderéé de la fonction cognitive » 24 January 2005 [online]. Available from URL: http://www.afssaps.sante.fr [Accessed 2005 Jan 28]

  37. AD2000 Collaborative Group. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomized double-blind trial. Lancet 2004; 363: 2105–15

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all members of the network of French Regional Centres of Pharmacovigilance. 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. Clinical Pharmacology Department, Centre of Pharmacoepidemiology and Drug Information, Pharmacoepidemiology Unit, Faculty of Medicine, Paul Sabateir University, 37 allées Jules Guesde, 31000, Toulouse, France

    Neda Tavassoli, Agnes Sommet, Maryse Lapeyre-Mestre, Haleh Bagheri & Jean-Louis Montrastruc

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  1. Neda Tavassoli
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  2. Agnes Sommet
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Correspondence to Neda Tavassoli.

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Tavassoli, N., Sommet, A., Lapeyre-Mestre, M. et al. Drug Interactions with Cholinesterase Inhibitors. Drug-Safety 30, 1063–1071 (2007). https://doi.org/10.2165/00002018-200730110-00005

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