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Impact of Medicine Withdrawal on Reporting of Adverse Events Involving Therapeutic Alternatives: A Study from the French Spontaneous Reporting Database

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Abstract

Introduction

The consequences of the withdrawal of marketing authorisation of drugs have mostly been studied considering drug prescription patterns for the therapeutic alternatives of the withdrawn drugs. The potential concomitant changes in the reporting of adverse reactions concerning these alternatives have been studied less often.

Objective

The objective of this study was to analyse the changes in the reporting of adverse events (AEs) for therapeutic alternatives after the withdrawal of three medicines (dextropropoxyphene, pioglitazone and tetrazepam) from the market for safety reasons.

Methods

This study was performed using both the French pharmacovigilance database and the Echantillon Généraliste des Bénéficiaires (a random sample of French health insurance affiliates). For dextropropoxyphene, pioglitazone and tetrazepam alternatives, the number and types of case reports were studied for both the year preceding the first official safety warning and the year following the withdrawal. Reporting rates expressed per 10,000 reimbursements (RRReimb) and per 10,000 treated patients (RRPat) were also compared for the two periods.

Results

After dextropropoxyphene withdrawal, case reports and reimbursements increased for tramadol (case reports: +23%, reimbursements: +13%) and codeine (case reports: +74%, reimbursements: +47%), RRPat being significantly increased for tramadol (0.92 vs. 1.06, p = 0.02). After pioglitazone withdrawal, case reports increased for dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides, and glucagon-like peptide 1 (GLP-1) analogues (+84%, +22% and +5%, respectively) and reimbursements (+55, +11 and +50%, respectively); both decreased for sulfonylureas (case reports: −6%, reimbursements: −2%). RRPat increased for DPP-4 inhibitors (1.63 vs. 2.26, p = 0.008). After tetrazepam withdrawal, case reports increased for diazepam, methocarbamol and thiocolchicoside (+110, +86 and +157%, respectively), as lesser did reimbursements. RRPat increased for diazepam (1.78 vs. 2.41, p = 0.054) and thiocolchicoside (0.14 vs. 0.24, p = 0.013).

Conclusion

For the three drug withdrawals investigated, the number of case reports involving alternatives increased to a larger extent than the numbers of prescriptions. This could relate to a higher occurrence of AEs in new users of alternatives who switched from the withdrawn medicines or to an increased awareness of possible AEs.

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Notes

  1. MedDRA® terminology is the international medical terminology developed under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The MedDRA® trademark is owned by the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) on behalf of the ICH.

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Acknowledgements

The authors would like to acknowledge ANSM (Agence Nationale de Sécurité du Médicament et des produits de santé).

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Authors and Affiliations

  1. University of Bordeaux, 33076, Bordeaux, France

    Cécile Pageot, Julien Bezin, Andy Smith, Mickael Arnaud, Bernard Bégaud & Antoine Pariente

  2. INSERM U1219, Bordeaux Population Health Research Center, Pharmacoepidemiology Team, 33076, Bordeaux, France

    Cécile Pageot, Julien Bezin, Andy Smith, Mickael Arnaud, Francesco Salvo, Françoise Haramburu, Bernard Bégaud & Antoine Pariente

  3. CHU Bordeaux, Service de Pharmacologie Médicale, Centre Régional de Pharmacovigilance de Bordeaux, 33076, Bordeaux, France

    Cécile Pageot, Julien Bezin, Francesco Salvo, Françoise Haramburu & Antoine Pariente

  4. Centre Régional de Pharmacovigilance, Hôpital Pellegrin-CHU de Bordeaux, 33076, Bordeaux Cedex, France

    Cécile Pageot & Françoise Haramburu

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  1. Cécile Pageot
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The French Network of Pharmacovigilance Centres

Corresponding author

Correspondence to Cécile Pageot.

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Funding

HEADS (HEAlth Determinants in Societies) is funded by IdEx (Initiative d’excellence) of Bordeaux University.

Conflict of interest

Cécile Pageot, Julien Bezin, Andy Smith, Mickael Arnaud, Francesco Salvo, Françoise Haramburu, Bernard Bégaud and Antoine Pariente have no conflicts of interest that are directly relevant to the content of this study.

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Pageot, C., Bezin, J., Smith, A. et al. Impact of Medicine Withdrawal on Reporting of Adverse Events Involving Therapeutic Alternatives: A Study from the French Spontaneous Reporting Database. Drug Saf 40, 1099–1107 (2017). https://doi.org/10.1007/s40264-017-0561-y

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  • DOI: https://doi.org/10.1007/s40264-017-0561-y

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