The association between automatic generic substitution and treatment persistence with oral bisphosphonates

Osteoporos Int. 2012 Aug;23(8):2201-9. doi: 10.1007/s00198-011-1850-4. Epub 2011 Nov 26.


Automatic generic substitution of alendronate products, used to reduce drug costs, and medication persistence was studied retrospectively between 2006 and 2009. During this period the number of, and the rate of substitution between, alendronate products increased while persistence decreased. Patient preferences should be considered when designing and evaluating generic policies.

Introduction: Automatic generic substitution (AGS) was implemented in Sweden in 2002. The objective of this study was to investigate the association between AGS and persistence with alendronate treatment of primary osteoporosis in Sweden.

Methods: An open historical cohort of women and men (n = 36,433) was identified in the Swedish Prescribed Drug Register through filled prescriptions for alendronate or risedronate between 2005 and 2009. Co-morbidity data was extracted from the National Patient Register. The association between AGS and medication persistence was investigated using non-parametric and parametric survival analysis.

Results: Between 2006 and 2009, the number of alendronate products increased from 15 to 25, the proportion of prescriptions constituting a substitution increased from 10.8% to 45.2%, and the proportion of patients persisting with alendronate treatment for 12 months fell from 66.9% to 51.7%. Patients starting alendronate treatment in 2006 had lower risk of stopping treatment compared with those starting in 2007 (HR 1.34, 95% CI 1.29-1.39), 2008 (HR 1.49, 95% CI 1.43-1.55), and 2009 (HR 1.50, 95% CI 1.40-1.60). No difference was observed in persistence with proprietary risedronate during the same period. Individuals who had their alendronate product substituted at the first prescription refill had significantly higher probability of discontinuation (HR 1.25, 95% CI 1.20-1.30).

Conclusion: AGS causes increased product substitution which appears to be associated with reduced treatment persistence. Poor health outcomes and associated costs due to forgone drug exposure should be taken into account in the design and evaluation of policies implemented to encourage utilisation of generic medicines.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Alendronate / administration & dosage
  • Bone Density Conservation Agents / administration & dosage*
  • Diphosphonates / administration & dosage*
  • Drug Substitution / statistics & numerical data*
  • Drugs, Generic / administration & dosage*
  • Etidronic Acid / administration & dosage
  • Etidronic Acid / analogs & derivatives
  • Female
  • Humans
  • Male
  • Medication Adherence / statistics & numerical data*
  • Osteoporosis / drug therapy*
  • Retrospective Studies
  • Risedronic Acid
  • Sweden / epidemiology
  • Time Factors


  • Bone Density Conservation Agents
  • Diphosphonates
  • Drugs, Generic
  • Risedronic Acid
  • Etidronic Acid
  • Alendronate