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Pharmacy World & Science

, Volume 29, Issue 4, pp 361–367 | Cite as

Unlicensed and off-label use of medicines at a neonatology clinic in Italy

  • Maria Dell’AeraEmail author
  • Anna Rita Gasbarro
  • Margherita Padovano
  • Nicola Laforgia
  • Donatella Capodiferro
  • Biagio Solarino
  • Roberto Quaranta
  • Alessandro S. Dell’Erba
Original Paper

Abstract

Objective

Many drugs used for children are not licensed or are used off-label. An increased risk of medication errors and unexpected adverse drug reactions (ADR) associated with off-label and unlicensed drug prescription has been reported. This risk increases in the newborn, who are more likely to be predisposed to an ADR due to their physiological immaturity. The objective of this study was to describe the use of unlicensed or off-label drugs in a Neonatal Intensive Care Unit (NICU).

Methods

All drugs prescribed to newborn admitted to the Neonatology Unit of Bari University Hospital, from July 1st to August 31st in 2004 were recorded.

Main outcome measures

All the drugs prescribed were analysed with regard to their license status, then the licensed drugs were compared to the indications, dose, route of administration, duration of treatment, contraindications and warnings specified in the summary of product characteristics of the marketing authorization.

Results

Data were collected on 176 prescriptions for 61 different drugs given to 34 newborns. Drugs were licensed in 88% and unlicensed in 12% of cases. About the licensed drugs, in 37.5% medicines were used following the terms of the marketing authorization, in 22.7% of cases medicines were used in an off-label manner as they contained no information for paediatric use in the marketing authorization and in 27.8% of cases medicines were licensed for paediatric use, but they were used off-label with regard to age, dose, route of administration and duration of treatment.

Conclusions

Despite European and American initiatives aiming to promote greater awareness and research in the paediatric population, these data demonstrate that there is still a high percentage of unlicensed or off-label drugs use in neonatology, underlining the need to stimulate scientific data collection by means of experimental studies or outcome research.

Keywords

Drug use Intensive care unit Italy Neonatology Off-label prescribing Unlicensed medicines 

Notes

Acknowledgements

The authors would like to thank Babett Pragnell for the support in the translation, Angela Mautone and Michele Lattarulo, the Chief of the Department of Biomedicine of Evolutive Age and the Chief of the Service of Pharmacy, respectively.

References

  1. 1.
    Legislative Decree n. 178 of 1991.Google Scholar
  2. 2.
    Kauffman RE. Status of drug approval processes and regulation of medications for children. Curr Opin Pediatr 1995;7:195–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Law n. 94 of 08 April 1998.Google Scholar
  4. 4.
    Avenel S, Bomkratz A, Dasssieu G, Janaud JC, Danan C. The incidence of prescriptions without marketing product licence in a neonatal intensive care unit. Arch Pediatr 2000;7:143–7.PubMedCrossRefGoogle Scholar
  5. 5.
    O’Donnell CP, Stone RS, Morley CJ. Unlicensed and Off-label drug use in an australian neonatal intensive care unit. Pediatrics 2002;110(5):e52.PubMedCrossRefGoogle Scholar
  6. 6.
    ‘t Jong GW, Vulto AG, de Hoog M, Schimmel KJ, Tibboel D, van den Anker JN. A survey of the use of off-label and unlicensed drugs in a Dutch children’s hospital. Pediatrics 2001;108:1089–93.PubMedCrossRefGoogle Scholar
  7. 7.
    ‘t Jong GW, Vulto AG, de Hoog M, Schimmel KJ, Tibboel D, van den Anker JN. Unapproved and off-label use of drugs in a children’s hospital. New Engl J Med 2000;343:1125.PubMedCrossRefGoogle Scholar
  8. 8.
    Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane A, et al. Survey of unlicensed and off-label drug use in European countries. BMJ 2000;320(7227):79–82.PubMedCrossRefGoogle Scholar
  9. 9.
    McIntyre J, Conroy S, Avery A, Corus H, Choonara I. Unlicensed and off-label prescribing of drugs in general practice. Arch Dis Child 2000;83:498–501.PubMedCrossRefGoogle Scholar
  10. 10.
    Ekins-Daukes S, Helms PJ, Simpson CR, Taylor MW, McLay JS. Off-label prescribing to children in primary care: retrospective observational study. Eur J Clin Pharmacol 2004;60(5):349–53.PubMedCrossRefGoogle Scholar
  11. 11.
    Pandolfini C, Impicciatore P, Provasi D, Rocchi F, Campi R, Bonati M, The Italian Paediatric Off-label Collaborative Group. Off-label use of drugs in Italy: a prospective, observational and multicentre study. Acta Pediatr 2002;91:339–47.CrossRefGoogle Scholar
  12. 12.
    Cuzzolin L, Zaccaron A, Fanos V, et al. Unlicensed and off-label uses of drugs in paediatrics: a review of the literature. Fundam Clin Pharmacol 2003;17(1):125–31.PubMedCrossRefGoogle Scholar
  13. 13.
    Conroy S, McIntyre J, Choonara I. Unlicensed and off-label drug use in neonates. Arch Dis Child Fetal Neonatal 1999;80:F142–5.CrossRefGoogle Scholar
  14. 14.
    US Food and Drug Administration. Class labeling for intranasal and orally inhaled corticosteroid containing drug products regarding the potential for growth suppression in children. Division of Pulmonary Drug Product. Rockville, MD: US Food and Drug Administration; November 9,1998. Talk Paper. Available at://www.fda.gov/cder/news/cs_label.htm.Google Scholar
  15. 15.
    ICH Topic E11: Clinical investigation of medicinal products in the paediatric population. European Agency for the Evaluation of Medicinal products, 2001.Google Scholar
  16. 16.
    Regulations requiring manufactures to assess the safety and effectiveness of new drugs and biological products in paediatric patients: final rule. Federal register 1998:66631–73.Google Scholar
  17. 17.
    10th Congress of the United States of America. Best pharmaceuticals for children Act, S.1789 109.Google Scholar
  18. 18.
    European Agency for the evaluation of Medicinal Products. Note for guidance on clinical investigation of medical products in children. London: European Agency for the Evaluation of Medicinal products, 1997.Google Scholar
  19. 19.
    CINECA—Society interuniversity. Progetto ARNO–Paediatrics, Report 2004. Bologna, Italy: Centauro s.r.l.;2005. ISBN 88-85980-46-5.Google Scholar
  20. 20.
    Official Gazette no. 227 29th of September 2005. AIFA: The independent research of drugs financed by AIFA.Google Scholar
  21. 21.
    Improving children’s medicines: EU reaches final agreement. IP/06/715; June 01 2006.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Maria Dell’Aera
    • 1
    Email author
  • Anna Rita Gasbarro
    • 1
  • Margherita Padovano
    • 1
  • Nicola Laforgia
    • 2
  • Donatella Capodiferro
    • 2
  • Biagio Solarino
    • 3
  • Roberto Quaranta
    • 3
  • Alessandro S. Dell’Erba
    • 3
  1. 1.Pharmacy University Hospital PoliclinicoBariItaly
  2. 2.Department of Biomedicine of Evolutive AgeUniversity Hospital PoliclinicoBariItaly
  3. 3.Department of Public and Internal MedicineUniversity Hospital PoliclinicoBariItaly

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