Osteoporosis International

, Volume 14, Issue 6, pp 507–514 | Cite as

Pharmacovigilance study of alendronate in England

  • Pipasha N. Biswas
  • Lynda V. Wilton
  • Saad A. W. Shakir
Original Article


Alendronate sodium is an aminobiphosphonate, an analog of inorganic pyrophosphate, indicated for the treatment of osteoporosis in post-menopausal women. We analyzed events reported in patients prescribed alendronate by general practitioners (GPs) in England. A non-interventional observational cohort study was conducted using the technique of prescription event monitoring (PEM). Exposure data were obtained from dispensed prescriptions issued between October 1995 and January 1997. Outcome data were obtained by sending questionnaires to prescribing GPs. The cohort comprised 11,916 patients. Events most frequently reported as suspected adverse drug reactions and reason for stopping alendronate were recognized gastrointestinal events listed in the Summary of Product Characteristics. These included nausea/vomiting, abdominal pain, dyspepsia, esophagitis and esophageal reflux. Events with the highest incidence density (ID1 per 1000 patient months treatment) were dyspeptic conditions (32.2), nausea/vomiting (20.8) and abdominal pain (13.8). The term dyspeptic conditions included dyspepsia, esophagitis, esophageal reflux, duodenitis, gastritis and heartburn. Serious suspected adverse reactions possibly related to alendronate were single reports of angioedema, erythema multiforme, hypercalcemia and hypocalcemia. There were 540 deaths in this elderly cohort. This study suggests that alendronate appears to be well tolerated, though there may be risk of developing gastrointestinal side effects including esophagitis and esophageal ulcers.


Alendronate Adverse events Esophagitis Prescription event monitoring 


  1. 1.
    WHO Study Group (1994) Assessment of fracture risk and its application to screening for post-menopausal osteoporosis. World Health Organisation, GenevaGoogle Scholar
  2. 2.
    Riggs BL, Melton LJ (1992) The prevention and treatment of osteoporosis. New Engl J Med 327:620–627Google Scholar
  3. 3.
    Rodan GA (1992) Introduction to bone biology. Bone 13:S3–6Google Scholar
  4. 4.
    Rodan GA, Balena R (1993) Biphosphonates in the treatment of metabolic bone diseases. Ann Med 25:373–378Google Scholar
  5. 5.
    Liberman UA, Weiss S, Broll J et al. (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 333:1437–1443Google Scholar
  6. 6.
    De Groen PC, Lubbe DF, Hirsch LJ, Daifotis A, Stephenson W, Freedholm D, Pryor-Tillotson S, Seleznick MJ, Pinkas H, Wang KK (1996) Esophagitis associated with the use of alendronate. N Engl J Med 335:1016–1021Google Scholar
  7. 7.
    Lufkin EG, Argueta R, Whitaker MD et al. (1994) Pamidronate: an unrecognised problem in gastrointestinal tolerability. Osteoporosis Int 4:320–322Google Scholar
  8. 8.
    Merck Sharp & Dohme (1996) Summary of Product Characteristics (partial revision of text) fosamax (alendronate sodium MSD)Google Scholar
  9. 9.
    Mann RD (1998) Prescription event monitoring—recent progress and future horizons. Br J Clin Pharmacol 46:195–201Google Scholar
  10. 10.
    COIMS/WHO (1993) International ethical guidelines for biomedical research involving human subjects. CIOMS/WHO, Geneva, SwitzerlandGoogle Scholar
  11. 11.
    Royal College of Physicians of London (1996) Guidelines on the practice of ethical committees in medical research involving human subjects. Royal College of Physicians of London, London, UKGoogle Scholar
  12. 12.
    Templeton L, Deeham A, Taylor C, Drummond C, Strang J (1997) Surveying general practitioners: does a low response rate matter? Br J Gen Pract 47:91–94Google Scholar
  13. 13.
    McAvoy BR, Kramer EFS (1996) General practice postal surveys: a questionnaire too far? BMJ 313:732–733Google Scholar
  14. 14.
    Inman W, Pearce GL (1993) Prescriber profile and post-marketing surveillance. Lancet 342:658–661Google Scholar
  15. 15.
    Kelly R, Taggart H (1997) Incidence of gastrointestinal side effects due to alendronate is high in clinical practice (letter) BMJ 315:1235Google Scholar
  16. 16.
    Mackay F, Mann RD (1998) Figures given in letter were prevalences, not incidences (letter). BMJ 316:1390Google Scholar
  17. 17.
    Kirby M (1998) Comparison group taking placebo should have been included (letter). BMJ 316:1389–1390Google Scholar
  18. 18.
    Young JH (1998) Manufacturer's comment (letter). BMJ 316:1390Google Scholar
  19. 19.
    Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC et al. (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541Google Scholar
  20. 20.
    Committee on Safety of Medicines (1996) Oesophageal reactions with alendronate sodium (Fosamax). Current Problems in Pharmacovigilance, vol 22Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2003

Authors and Affiliations

  • Pipasha N. Biswas
    • 1
  • Lynda V. Wilton
    • 1
    • 2
  • Saad A. W. Shakir
    • 1
    • 2
  1. 1.Drug Safety Research UnitBursledon HallSouthamptonUK
  2. 2.University of PortsmouthPortsmouthUK

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