Skip to main content

Proactive Regional Pharmacovigilance System Versus National Spontaneous Reporting for Collecting Safety Data on Concerning Off-Label Prescribing Practices: An Example with Baclofen and Alcohol Dependence in France

A Letter to the Editor to this article was published on 10 February 2017

Abstract

Introduction

Off-label prescribing (OLP) may raise serious safety concerns that traditional spontaneous reporting of adverse drug reactions (ADRs) may not identify in a timely manner. In France, the ‘Multidisciplinary Consultation Service for Off-Label Prescribing in Addiction Medicine’ (CAMTEA) is a proactive regional system established to identify ADRs associated with the OLP of baclofen for alcohol dependence.

Objective

The aim was to demonstrate, using the French pharmacovigilance database (FPVD), that CAMTEA allowed for the reporting of a substantial amount of ADRs, comparable in nature to those provided via spontaneous reporting.

Method

The 2012–2013 FPVD notifications associated with baclofen OLP were extracted. The ten most frequent types of ADRs among ‘serious’ and ‘non-serious’ reports were listed. The frequency of each type of ADR was compared between CAMTEA and spontaneous reporting, and the magnitudes of the differences were assessed using standardized differences.

Results

A total of 428 baclofen reports (1043 ADRs) were identified, among which 221 (51.64%) originated from CAMTEA. The ten most frequent ADRs in ‘serious’ reports were (1) confusion (17.3%), (2) seizures (11.5%), (3) drowsiness/sedation (11.5%), (4) agitation (10.9%), (5) coma (9.6%), (6) hallucinations (7.7%), (7) falls (7.1%), (8) behavioral disorders (5.8%), (9) withdrawal syndrome (5.1%), and (10) space–time disorientation (5.1%). A standardized difference of <0.2 was identified for six out of the ten most frequent ‘serious’ ADRs, and eight of the ten ‘non-serious’ ADRs.

Conclusion

A proactive regional pharmacovigilance system could collect a substantial amount of safety data on a specific OLP practice. The profile of the ADRs collected was similar to that seen in the nationwide spontaneous reporting system.

This is a preview of subscription content, access via your institution.

References

  1. Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006;166:1021–6.

    Article  PubMed  Google Scholar 

  2. Dresser R, Frader J. Off-label prescribing: a call for heightened professional and government oversight. J Law Med Ethics. 2009;37(476–86):396.

    Google Scholar 

  3. Dal Pan GJ. Monitoring the safety of medicines used off-label. Clin Pharmacol Ther. 2012;91:787–95.

    Article  Google Scholar 

  4. Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM). Baclofène: Résumé des Caractéristiques Produit [Baclofen: summary of product characteristics]. 2013. http://agence-prd.ansm.sante.fr/php/ecodex/rcp/R0232890.htm. Accessed 20 Nov 2016.

  5. Rolland B, Bordet R, Cottencin O. Alcohol-dependence: the current French craze for baclofen. Addiction. 2012;107:848–9.

    Article  PubMed  Google Scholar 

  6. Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM). Mise en garde sur l’utilisation hors AMM du baclofène dans le traitement de l’alcoolo-dépendance [Cautionary statement regarding the off-label use of baclofen in the treatment of alcohol dependence]. 2011. http://ansm.sante.fr/var/ansm_site/storage/original/application/b88517d4324d10054712c930f22c464b.pdf. Accessed 20 Nov 2016.

  7. Comité Technique National de Pharmacovigilance. Effets indésirables du baclofène dans le traitement des addictions. Suivi national de pharmacovigilance: année 2011 [Baclofen-related adverse reactions in the treatment of addiction. 2011 national pharmacovigilance monitoring]. http://ansm.sante.fr/content/…/baclofene–suivi-pharmacovigilance-2011.pdf. Accessed 20 Nov 2016.

  8. Rolland B, Deheul S, Danel T, Bordet R, Cottencin O. A system of prescriptions without drug approval: example of baclofen. Therapie. 2010;65:511–8.

    Article  PubMed  Google Scholar 

  9. Rolland B, Deheul S, Danel T, Bence C, Blanquart M-C, Bonord A, et al. Temporary recommendation for use on off-label baclofen: viewpoint of prescribers of the CAMTEA system. Therapie. 2015;70:235–8.

    Article  Google Scholar 

  10. Food and Drug Administration. What is a serious adverse event? 2016. http://www.fda.gov/Safety/MedWatch/HowToReport/ucm053087.htm. Accessed 20 Nov 2016.

  11. Chaignot C, Weill A, Ricordeau P, Alla F. Use in France of baclofen for alcohol dependence from 2007 to 2013: cohort study based on the databases SNIIRAM and PMSI. Therapie. 2015;70:443–53.

    Article  PubMed  Google Scholar 

  12. Rawlins MD. Spontaneous reporting of adverse drug reactions. I: the data. Br J Clin Pharmacol. 1988;26:1–5.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Smith CC, Bennett PM, Pearce HM, Harrison PI, Reynolds DJ, Aronson JK, et al. Adverse drug reactions in a hospital general medical unit meriting notification to the Committee on Safety of Medicines. Br J Clin Pharmacol. 1996;42:423–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Rolland B, Deheul S, Danel T, Bordet R, Cottencin O. A case of de novo seizures following a probable interaction of high-dose baclofen with alcohol. Alcohol Alcohol. 2012;47:577–80.

    CAS  Article  PubMed  Google Scholar 

  15. Rolland B, Labreuche J, Duhamel A, Deheul S, Gautier S, Auffret M, et al. Baclofen for alcohol dependence: relationships between baclofen and alcohol dosing and the occurrence of major sedation. Eur Neuropsychopharmacol. 2015;25:1631–6.

    CAS  Article  PubMed  Google Scholar 

  16. Rolland B, Valin T, Langlois C, Auffret M, Gautier S, Deheul S, et al. Safety and drinking outcomes among patients with comorbid alcohol dependence and borderline personality disorder treated with high-dose baclofen: a comparative cohort study. Int Clin Psychopharmacol. 2015;30:49–53.

    Article  PubMed  Google Scholar 

  17. Bence C, Cottencin O, Deheul S, Gautier S, Bordet R, Rolland B. Baclofen-induced edema in alcohol use disorders. J Clin Pharmacol. 2014;54:478–81.

    Article  PubMed  Google Scholar 

  18. Rolland B, Jaillette E, Carton L, Bence C, Deheul S, Saulnier F, et al. Assessing alcohol versus baclofen withdrawal syndrome in patients treated with baclofen for alcohol use disorder. J Clin Psychopharmacol. 2014;34:153–6.

    CAS  Article  PubMed  Google Scholar 

  19. Auffret M, Rolland B, Deheul S, Loche V, Hennaux C, Cottencin O, et al. Severe tinnitus induced by off-label baclofen. Ann Pharmacother. 2014;48:656–9.

    Article  PubMed  Google Scholar 

  20. Geoffroy PA, Auffret M, Deheul S, Bordet R, Cottencin O, Rolland B. Baclofen-induced manic symptoms: case report and systematic review. Psychosomatics. 2014;55:326–32.

    Article  PubMed  Google Scholar 

  21. Rolland B, Auffret M, Franchitto N. Safety reports on the off-label use of baclofen for alcohol-dependence: recommendations to improve causality assessment. Expert Opin Drug Saf. 2016;15:1–5.

    Article  Google Scholar 

  22. Gerlach M, Egberts K, Dang S-Y, Plener P, Taurines R, Mehler-Wex C, et al. Therapeutic drug monitoring as a measure of proactive pharmacovigilance in child and adolescent psychiatry. Expert Opin Drug Saf. 2016;15:1477–82.

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the addiction specialists who took part in the CAMTEA system: Drs. Ali Benani, Alexandre Bonord, Thierry Briand, Catherine Carpeza, Arnaud Didier, Didier Doutriaux, Christelle Dubocage, Damien Duquesne, François Germe, Bernard Gibour, Dorothée Hennebelle, Michaël Henon, François Lefebvre, Xavier Loosfeld, Christian Maton, Lucie Molmy, Catherine Nedelec, Richard Quesney, Thierry Renaux, Cécile Richez, Marina Rose, François Sarasy, Robin Semal, Laure Spinozi, Michel Sochala, Ghassan Takkiedine, Elodie Vernalde, Véronique Vosgien, and Jacques Yguel. We also thank the network of French pharmacovigilance centers, especially the Grenoble and Paris–Fernand Widal centers, for their involvement in the national ADR reporting on off-label baclofen. We wish to direct a special thought to the late Céline Villiers for her precious work on the pharmacovigilance of baclofen in France.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Benjamin Rolland.

Ethics declarations

Benjamin Rolland was the main investigator of a study on baclofen funded by Ethypharm, and he has received fees for lectures or consultancy from Lundbeck, Indivior, AstraZeneca, Bristol-Myers-Squibb, Servier, and Ethypharm. Regis Bordet has received fees for lectures or consultancy from Lundbeck, Otsuka, and Novartis. Olivier Cottencin was an associate investigator in a clinical trial funded by Ethypharm. He has received sponsorship to attend scientific meetings from Lundbeck, BMS, Otsuka, Janssen Cilag, Reckitt Benckiser, Pfizer, and Bouchara Recordati. Sylvie Deheul worked as an independent expert for Ethypharm (independent monitoring committee of a phase I trial). Marine Auffret, Julien Labreuche, Alain Duhamel, and Sophie Gautier declare no conflicts of interest related to this article.

Funding

No sources of funding were used to assist in the preparation of this study.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Auffret, M., Labreuche, J., Duhamel, A. et al. Proactive Regional Pharmacovigilance System Versus National Spontaneous Reporting for Collecting Safety Data on Concerning Off-Label Prescribing Practices: An Example with Baclofen and Alcohol Dependence in France. Drug Saf 40, 257–262 (2017). https://doi.org/10.1007/s40264-016-0489-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40264-016-0489-7

Keywords

  • Alcohol Dependence
  • Baclofen
  • Withdrawal Syndrome
  • Spontaneous Reporting
  • Spontaneous Reporting System