Drug Safety

, Volume 35, Issue 4, pp 315–323 | Cite as

Cardiovascular, Ocular and Bone Adverse Reactions Associated with Thiazolidinediones

A Disproportionality Analysis of the US FDA Adverse Event Reporting System Database
  • Domenico Motola
  • Carlo Piccinni
  • Chiara Biagi
  • Emanuel Raschi
  • Anna Marra
  • Giulio Marchesini
  • Elisabetta Poluzzi
Original Research Articles

Abstract

Background: The risk of myocardial infarction, macular oedema and bone fractures associated with thiazolidinediones (TZDs) has been extensively investigated.

Objective: The aim of the study was to verify if the analysis of a large spontaneous reporting database could generate early signals on these adverse drug reactions (ADRs) associated with TZDs.

Methods: A case/non-case study, restricted to antidiabetic drugs, was performed on spontaneous reports of ADRs (2005–2008) in the US FDA Adverse Event Reporting System (AERS). The method was applied to TZDs, both as a drug class and as single agents. The reporting odds ratio (ROR) with 95% CI was calculated as a measure of disproportionality in the whole dataset and in a quarter-by-quarter analysis.

Results: TZD use was registered in 49 589 out of 301 950 drug-reaction pairs (16%), with significant disproportionality for myocardial infarction (ROR 4.71; 95%CI 4.40, 5.05), macular oedema (3.88; 2.79, 5.39) and bone fractures (1.73; 1.53, 1.96). Separate analysis of the two TZDs showed that only rosiglitazone was associated with myocardial infarction (7.86; 7.34, 8.34) and macular oedema (5.55; 3.94, 7.79), whereas pioglitazone was associated with multiple site fractures (2.00; 1.70, 2.35), in particular upper and lower limb and pelvic fractures. The quarter-by-quarter analysis identified disproportionality for myocardial infarction (3.13; 2.38, 4.10) and bone fractures since January-March 2005 (2.70; 1.04, 2.78).

Conclusions: The frequency of reporting of myocardial infarction, macular oedema and fractures was significantly higher for TZDs in comparison with other antidiabetic drugs, with large intraclass differences. Both myocardial infarction and bone fracture signals appeared before major publications on these safety issues.

Notes

Acknowledgements

This research was supported by institutional funds from the University of Bologna. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Copyright information

© Adis Data Information BV. 2012

Authors and Affiliations

  • Domenico Motola
    • 1
  • Carlo Piccinni
    • 1
  • Chiara Biagi
    • 1
  • Emanuel Raschi
    • 1
  • Anna Marra
    • 2
  • Giulio Marchesini
    • 3
  • Elisabetta Poluzzi
    • 1
  1. 1.Department of PharmacologyUniversity of BolognaBolognaItaly
  2. 2.Pharmacy ServiceUniversity Hospital of FerraraFerraraItaly
  3. 3.Metabolic Diseases & Clinical Dietetics, Department of Clinical MedicineUniversity of BolognaBolognaItaly

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