Drug Safety

, Volume 24, Issue 10, pp 781–792

Postdischarge Adverse Drug Reactions in Primary Care Originating from Hospital Care in France

A Nationwide Prospective Study
  • Laurent Letrilliart
  • Thomas Hanslik
  • Michel Biour
  • Jean-Paul Fagot
  • Marguerite Guiguet
  • Antoine Flahault
Original Research Article


Objective: To describe and estimate the incidence and preventability of postdischarge adverse drug reactions (ADRs) detected in primary care in France.

Design: Prospective study of patients referred to hospital by participating general practitioners (GPs). These GPs reported all cases of an adverse reaction to a drug instituted in hospital among patients who consulted them within 30 days of discharge.

Setting: 305 general practices from all French regions.

Patients: 7540 patients referred by GPs to private or public hospitals.

Main outcome measures: The incidence for postdischarge ADRs in primary care, and their preventability.

Results: 30 cases of postdischarge ADR were detected in 29 re-consulting patients, yielding a minimal incidence for France of 0.4 per 100 admissions (95% confidence interval 0.3 to 0.6). The ADRs were assessed as serious in 60% of cases. The main drug classes implicated were cardiovascular drugs (8 ADRs), oral anticoagulants (6), psychoactive drugs (4), antidiabetics (3), and opioid analgesics (3). Patients experiencing a postdischarge ADR were older than patients not experiencing one (median age: 77 vs 68 years; p = 0.004). Detected ADRs were considered preventable in 59% of cases.

Conclusions: Physicians and patients should be aware of the possible occurrence of postdischarge ADRs. Patient information in hospital, close postdischarge follow-up of patients at risk, and appropriate transmission of information between hospital physicians and GPs can help to prevent them.


  1. 1.
    Larazou J, Pomeranz B, Corey P. Incidence of adverse drug reactions in hospitalized patients. JAMA 1998; 279: 1200–5CrossRefGoogle Scholar
  2. 2.
    Imbs J, Pouyanne P, Haramburu F, et al. Iatrogenie médicamenteuse: estimation de sa prévalence dans les hôpitaux publics français. Thérapie 1999; 54: 21–7PubMedGoogle Scholar
  3. 3.
    Ministère de l’Emploi et de la Solidarité. Annuaire des Statistiques Sanitaires et Sociales. 1998 ed. Paris: SESI, 1999Google Scholar
  4. 4.
    Pokras R, Kozak L, McCarthy E, et al. Trends in Hospital Utilization, 1965-86. Am J Public Health 1990; 80: 488–90PubMedCrossRefGoogle Scholar
  5. 5.
    Klein U, Klein M, Sturm H, et al. The frequency of adverse drug reactions as dependent upon age, sex, and duration of hospitalization. Int J Clin Pharmacol 1976; 13: 187–95Google Scholar
  6. 6.
    Weigelt J, Dryer D, Haley R. The necessity and efficiency of wound surveillance after discharge. Arch Surg 1992; 127: 77–82PubMedCrossRefGoogle Scholar
  7. 7.
    Iezzoni L, Mackiernan Y, Chalane M, et al. Screening inpatient quality using post-discharge events. Med Care 1999; 37: 384–98PubMedCrossRefGoogle Scholar
  8. 8.
    Valleron A, Garnerin P. Computer networking as a tool for public health surveillance: the French experiment. MMWR Morb Mortal Wkly Rep 1992; 41: 101–10PubMedGoogle Scholar
  9. 9.
    Letrilliart L, Flahault A, Guiguet M, et al. Observation épidémiologique nationale de la filière ville-hôpital grâce au Réseau Sentinelles [online]. Available from: URL: http://www.b3e.jussieu.fr/sentiweb/fr/bulletins/lepointsur/index.html [Accessed 2001 Jul 5]
  10. 10.
    Official Journal of the European Communities. Commission directive on the approximation of provisions laid down by law, regulation or administrative action relative to medicinal products [online]. Available from: URL: http://europa.eu.int/smartapi/cgi/sga_doc?smartapi!celexapi!prod!CELEXnumdoc&lg=en&numdoc=32000L0038&model=guichett [Accessed 2001 Jul 5]
  11. 11.
    Edwards I, Biriell C. Harmonisation in pharmacovigilance. Drug Saf 1994; 10: 93–102PubMedCrossRefGoogle Scholar
  12. 12.
    Keissler D. Introducing MEDWatch: a new approach to reporting medication and device adverse effects and product problems. JAMA 1993; 269: 2765–8CrossRefGoogle Scholar
  13. 13.
    Benichou C. Imputability of unexpected or toxic drug reactions. In: Benichou C, Bouche P, Caron J, et al., editors. Adverse drug reactions. A practical guide to diagnosis and management. New York (NY): J Wiley & Sons, 1994: 271–5Google Scholar
  14. 14.
    Imbs JL, Pletan Y, Spriet A. Evaluation de la iatrogènese médicamenteuse évitable: méthodologie. Thérapie 1998; 53: 365–70PubMedGoogle Scholar
  15. 15.
    Banque de Données Automatisée sur les Médicaments (BIAM) [online]. Available from: URL: http://www2.biam2.org/acceuil.html [Accessed 2001 Jul 5]
  16. 16.
    Vidal dictionary. 76th ed. Paris: Editions du Vidal, 2000Google Scholar
  17. 17.
    Gardner M, Altman D. Statistics with confidence: confidence intervals and statistical guidelines. London: BMJ Books, 1989: 116–8Google Scholar
  18. 18.
    Spino M, Sellers E, Kaplan H, et al. Adverse biochemical and clinical consequences of furosemide administration. Can Med Assoc J 1978; 118: 1513–8PubMedGoogle Scholar
  19. 19.
    Pillans P, Coulter D, Black P. Angiooedema and urticaria with angiotensin converting inhibitors. Eur J Clin Pharmacol 1996; 51: 123–6PubMedCrossRefGoogle Scholar
  20. 20.
    Skjelbred P. The effects of acetylsalicylic acid on swelling, pain and other events after surgery. Br J Clin Pharmacol 1984; 17: 379–84PubMedCrossRefGoogle Scholar
  21. 21.
    van Kraaij DJ, Jansen R, Bouwels L, et al. Furosemide withdrawal in elderly heart failure patients with preserved left ventricular systolic function. Am J Cardiol 2000; 85: 1461–6PubMedCrossRefGoogle Scholar
  22. 22.
    Dukes M. Meyler’s side effects of drugs. 13th ed. Amsterdam: Elsevier Science Publishers, 1996Google Scholar
  23. 23.
    McAreavey D, Robertson J. Angiotensin converting enzyme inhibitors and moderate hypertension. Drugs 1990; 40: 326–45PubMedCrossRefGoogle Scholar
  24. 24.
    The European atrial fibrillation trial study group. Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. N Engl J Med 1995; 333: 5–10Google Scholar
  25. 25.
    Fava M, Rosenbaum J, Hoog S, et al. Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression. J Affect Disord 2000; 59: 119–26PubMedCrossRefGoogle Scholar
  26. 26.
    Bocksberger J, Gex-Fabry M, Gauthey L, et al. Clomipramine therapy in the geriatric drug monitoring. Ther Drug Monit 1994; 16: 113–9PubMedCrossRefGoogle Scholar
  27. 27.
    Egbert A, Parks L, Short L, et al. Randomized trial of postoperative patient-controlled analgesia vs intramuscular narcotics in frail elderly men. Arch Intern Med 1990; 150: 1897–903PubMedCrossRefGoogle Scholar
  28. 28.
    United Kingdom Prospective Diabetes Study Group. United Kingdom prospective diabetes study (UKPDS) 13: relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. BMJ 1995; 310: 83–8Google Scholar
  29. 29.
    Ytterberg S, Mahowald M, Woods S. Codeine and oxycodone use in patients with chronic rheumatic disease pain. Arthritis Rheum 1998; 41: 1603–2PubMedCrossRefGoogle Scholar
  30. 30.
    Kjaersgaard-Andersen P, Nafei A, Skov O, et al. Codeine plus paracetamol versus paracetamol in longer-term treatment of chronic pain due to osteoarthritis of the hip: a randomised, double-blind, multi-centre study. Pain 1990; 43: 309–18PubMedCrossRefGoogle Scholar
  31. 31.
    Wilton L, Pearce G, Mann R. A comparison of ciprofloxacin, norfloxacine, ofloxacine, azithromycin and cefixime examined by observational cohort studies. Br J Clin Pharmacol 1996; 41: 277–84PubMedCrossRefGoogle Scholar
  32. 32.
    Royer R. Adverse drug reactions with fluoroquinolones. Therapie 1996; 51: 414–6PubMedGoogle Scholar
  33. 33.
    Frykman E, Bystrom M, Jansson U, et al. Side effects of iron supplements in blood donors: Superior tolerance of heme iron. J Lab Clin Med 1994; 123: 561–4PubMedGoogle Scholar
  34. 34.
    Perry M, Eaton W, Propert K, et al. Chemotherapy with or without radiation therapy in limited small-cell carcinoma of the lung. N Engl J Med 1987; 316: 912–8PubMedCrossRefGoogle Scholar
  35. 35.
    Crawford J, Ozer H, Stoller R, et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 1991; 325: 164–70PubMedCrossRefGoogle Scholar
  36. 36.
    Miremont G, Haramburu F, Begaud B, et al. Adverse drug reactions: physicians’ opinions versus a causality assessment method. Eur J Clin Pharmacol 1994; 46: 285–9PubMedCrossRefGoogle Scholar
  37. 37.
    Kellaway GS. Intensive monitoring for adverse drug effects in patients discharged from acute medical wards. NZ Med J 1973; 78: 525–8Google Scholar
  38. 38.
    Moride Y, Haramburu F, Requejo A, et al. Under-reporting of adverse drug reactions in general practice. Br J Clin Pharmacol 1997; 43: 177–81PubMedCrossRefGoogle Scholar
  39. 39.
    Frankl S, Breeling J, Goldman L. Preventability of emergent hospital readmission. Am J Med 1991; 90: 667–74PubMedGoogle Scholar
  40. 40.
    Hewitt J. Drug-related unplanned readmissions to hospital. Aust J Hosp Pharm 1995; 25: 400–3Google Scholar
  41. 41.
    Mouquet M, Joubert M, Tudeau L. Les pathologies prises en charge à l’hôpital. Direction de la Recherche, des Etudes et de l’Evaluation et des Statistiques, Ministère de l’Emploi et de la Solidarité. Etudes et résultats 1999; 41: 1–8Google Scholar
  42. 42.
    Moore N, Lecointre D, Noblet C, et al. Frequency and cost of serious adverse drug reactions in a department of general medicine. Br J Clin Pharmacol 1998; 45: 301–8PubMedCrossRefGoogle Scholar
  43. 43.
    Hurwitz N. Predisposing factors in adverse drug reactions to drug. BMJ 1969; 1: 536–9PubMedCrossRefGoogle Scholar
  44. 44.
    Gurwitz J, Avorn J. The ambiguous relation between aging and adverse drug reactions. Ann Intern Med 1991; 114: 956–66PubMedGoogle Scholar
  45. 45.
    Leape L, Brennan T, Laird N, et al. The nature of adverse events in hospitalized patients: results of the Harvard Medical Practice Study II. N Engl J Med 1991; 324: 377–84PubMedCrossRefGoogle Scholar
  46. 46.
    Bates D, Miller E, Cullen D, et al. Patient risk factors for adverse drug events in hospitalized patients. Arch Intern Med 1999; 159: 2553–60PubMedCrossRefGoogle Scholar
  47. 47.
    Beers M, Dang J, Hasegawa J, et al. Influence of hospitalization on drug therapy in the elderly. J Am Geriatr Soc 1989; 37: 679–83PubMedGoogle Scholar
  48. 48.
    Omori D, Potyk R, Kroenke K. The adverse effects of hospitalization on drug regimens. Arch Intern Med 1991; 151: 1562–4PubMedCrossRefGoogle Scholar
  49. 49.
    Seeger J, Kong S, Schumock G. Characteristics associated with ability to prevent adverse drug reactions in hospitalized patients. Pharmacotherapy 1998; 18: 1284–9PubMedGoogle Scholar
  50. 50.
    Bates D, Leape L, Petrycki S. Incidence and preventability of adverse drug events in hospitalized adults. J Gen Intern Med 1991; 8: 289–94CrossRefGoogle Scholar
  51. 51.
    Bates D, Cullen D, Laird N, et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. JAMA 1995; 274: 29–34PubMedCrossRefGoogle Scholar
  52. 52.
    Pearson T, Pittman D, Longley J, et al. Factors associated with preventable adverse drug reactions. Am J Hosp Pharm 1994; 51: 2268–72.PubMedGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Laurent Letrilliart
    • 1
  • Thomas Hanslik
    • 2
  • Michel Biour
    • 3
  • Jean-Paul Fagot
    • 1
  • Marguerite Guiguet
    • 1
  • Antoine Flahault
    • 1
  1. 1.INSERM Unit 444, WHO Collaborating Centre for Electronic Disease SurveillanceNational Institute for Health and Medical Research (INSERM), Université Paris 6ParisFrance
  2. 2.Department of Internal MedicineAmbroise-Paré Hospital, Boulogne-Billancourt, and Université Paris 5ParisFrance
  3. 3.Regional Centre for Pharmacovigilance and Drug InformationSaint-Antoine HospitalParisFrance

Personalised recommendations