Drug Safety

, Volume 40, Issue 3, pp 257–262 | Cite as

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

  • Marine Auffret
  • Julien Labreuche
  • Alain Duhamel
  • Sylvie Deheul
  • Olivier Cottencin
  • Régis Bordet
  • Sophie Gautier
  • Benjamin Rolland
Original Research Article

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.

References

  1. 1.
    Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006;166:1021–6.CrossRefPubMedGoogle Scholar
  2. 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. 3.
    Dal Pan GJ. Monitoring the safety of medicines used off-label. Clin Pharmacol Ther. 2012;91:787–95.CrossRefGoogle Scholar
  4. 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. 5.
    Rolland B, Bordet R, Cottencin O. Alcohol-dependence: the current French craze for baclofen. Addiction. 2012;107:848–9.CrossRefPubMedGoogle Scholar
  6. 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. 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. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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. 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.CrossRefPubMedGoogle Scholar
  12. 12.
    Rawlins MD. Spontaneous reporting of adverse drug reactions. I: the data. Br J Clin Pharmacol. 1988;26:1–5.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Marine Auffret
    • 1
  • Julien Labreuche
    • 2
  • Alain Duhamel
    • 2
  • Sylvie Deheul
    • 3
  • Olivier Cottencin
    • 4
    • 5
  • Régis Bordet
    • 1
    • 3
    • 6
  • Sophie Gautier
    • 1
    • 6
  • Benjamin Rolland
    • 4
    • 6
  1. 1.Centre Régional de Pharmacovigilance, CHU LilleLille CedexFrance
  2. 2.Univ. Lille, CHU Lille, EA 2694 - Santé Publique: épidémiologie et qualité des soinsLilleFrance
  3. 3.Service d’Addictovigilance, CHU LilleLille CedexFrance
  4. 4.Service d’AddictologieCHU LilleLille CedexFrance
  5. 5.ScaLAB UMR 9193Univ LilleLille CedexFrance
  6. 6.Département de Pharmacologie MédicaleINSERM U1171 Univ LilleLille CedexFrance

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