Skip to main content
SpringerLink
Log in

Unlicensed and Off-Label Drug Use in Children

Implications for Safety

  • Current Opinion
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

A significant number of children receive either an unlicensed or an off-label drug during their stay in hospital. Studies throughout Europe have shown that at least one-third of children in hospital and up to 90% of neonates in a neonatal intensive care unit receive such drug prescriptions. The medicines that are most frequently used off-label include analgesics, antibiotics and bronchodilators. The purpose of licensing a drug is to ensure safety, efficacy and quality. If a drug is used in a different manner, one would expect a greater risk of toxicity. Only three studies have commented on the risk of toxicity in relation to unlicensed or off-label drug use. Only one of these three studies prospectively tried to evaluate the risk associated with off-label and unlicensed drug prescription. This study suggested that the percentage of unlicensed and off-label drug use was significantly associated with the risk of an adverse drug reaction. Two studies looking at adverse drug reactions suggest that there is a greater risk of a severe adverse drug reaction occurring in association with the off-label or unlicensed use of drugs. One study found that five out of eight severe adverse drug reactions were associated with the off-label use of a medicine. The other study found that 14 of 19 drug prescriptions associated with 17 severe adverse drug reactions were either unlicensed or off-label. The risk of prescribing off-label and unlicensed drugs in children is not clear from the limited data available.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV

Similar content being viewed by others

References

  1. Shirkey H. Therapeutic orphans. J Pediatr 1968; 72: 119–20

    Article  PubMed  CAS  Google Scholar 

  2. Sutherland JM. Fatal cardiovascular collapse of infants receiving large amounts of chloramphenicol. Am J Dis Child 1959: 7

  3. Weiss CF, Glazko AJ, Weston JK. Chloramphenicol in the newborn infant. N Engl J Med 1960; 262: 787–94

    Article  PubMed  CAS  Google Scholar 

  4. Lenz W. Epidemiology of congenital malformations. Ann N Y Acad Sci 1965; 123: 228–36

    Article  PubMed  CAS  Google Scholar 

  5. Choonara I, Dunne J. Licensing of medicines. Arch Dis Child 1998; 78: 402–3

    Article  PubMed  CAS  Google Scholar 

  6. Turner S, Nunn AJ, Choonara I. Unlicensed drug use in children in the U.K. Paed Perinatal Drug Ther 1997; 1: 52–5

    Google Scholar 

  7. Turner S, Gill A, Nunn T, et al. Use of ‘off-label’and unlicensed drugs in paediatric intensive care unit. Lancet 1996; 347: 549–50

    Article  PubMed  CAS  Google Scholar 

  8. McKinzie JP, Wright SW, Wrenn KD. Pediatric drug therapy in the emergency department; does it meet FDA-approved prescribing guidelines? Am J Emerg Med 1997; 15: 118–21

    Article  PubMed  CAS  Google Scholar 

  9. Turner S, Longworth A, Nunn AJ, et al. Unlicensed drug use on paediatric wards. BMJ 1998; 316: 343–5

    Article  PubMed  CAS  Google Scholar 

  10. Turner S, Nunn AJ, Fielding K, et al. Adverse drug reactions to unlicensed and off-label drugs on paediatric wards: a prospective study. Acta Paediatr 1999; 88: 965–8

    Article  PubMed  CAS  Google Scholar 

  11. Turner S. Unregistered and off-label drug use in paediatric inpatients. Aust J Hosp Pharm 1999; 29: 265–8

    Google Scholar 

  12. Conroy S, Choonara I, Impicciatore P, et al. Survey of unlicensed and off-label drug use in paediatric wards in European countries. BMJ 2000; 320: 79–82

    Article  PubMed  CAS  Google Scholar 

  13. Conroy S, McIntyre J, Choonara I. Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed 1999; 80: F142–5

    Article  PubMed  CAS  Google Scholar 

  14. Wilton LV, Pearce G, Mann RD. The use of newly marketed drugs in children and adolescents prescribed in general practice. Pharmacoepidemiol Drug Saf 1999; 8: S37–45

    Article  PubMed  Google Scholar 

  15. McIntyre J, Conroy S, Avery A, et al. Unlicensed and off label prescribing of drugs in general practice. Arch Dis Child 2000; 83: 498–501

    Article  PubMed  CAS  Google Scholar 

  16. Chalumeau M, Treluyer JM, Salanave B, et al. Off label and unlicensed drug use among French office based paediatricians. Arch Dis Child 2000; 83: 502–5

    Article  PubMed  CAS  Google Scholar 

  17. Jong GW, Vulto AG, de Hoog M, et al. Unapproved and off-label use of drugs in a children’s hospital. N Engl J Med 2000; 343: 1125

    Article  PubMed  Google Scholar 

  18. Impicciatore P, Choonara I. Status of new medicines approved by the European Medicines Evaluation Agency regarding paediatric use. Br J Clin Pharmacol 1999; 48: 15–8

    Article  PubMed  CAS  Google Scholar 

  19. Impicciatore P, Choonara I, Clarkson A, et al. Incidence of adverse drug reactions in paediatric in/out-patients: a systematic review and meta-analysis of prospective studies. Br J Clin Pharmacol 2001; 52: 77–83

    Article  PubMed  CAS  Google Scholar 

  20. Gill AM, Leach HJ, Hughes J, et al. Adverse drug reactions in a paediatric intensive care unit. Acta Paediatr 1995; 84: 438–41

    Article  PubMed  CAS  Google Scholar 

  21. Clarkson A, Ingleby E, Choonara I, et al. A novel scheme for the reporting of adverse drug reactions. Arch Dis Child 2001; 84: 337–9

    Article  PubMed  CAS  Google Scholar 

  22. Hughes J, Leach HJ, Choonara I. Hallucinations on withdrawal of isoflurane used as sedation. Acta Paediatr 1993; 82: 885–6

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Academic Division of Child Health, University of Nottingham, Derbyshire Children’s Hospital, Uttoxeter Road, Derby, DE22 3NE, UK

    Imti Choonara & Sharon Conroy

Authors
  1. Imti Choonara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharon Conroy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Imti Choonara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choonara, I., Conroy, S. Unlicensed and Off-Label Drug Use in Children. Drug-Safety 25, 1–5 (2002). https://doi.org/10.2165/00002018-200225010-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200225010-00001

Keywords

Search

Navigation