Drug Safety

, Volume 25, Issue 1, pp 1–5 | Cite as

Unlicensed and Off-Label Drug Use in Children

Implications for Safety
  • Imti ChoonaraEmail author
  • Sharon Conroy
Current Opinion


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.


Adverse Drug Reaction Drug Prescription Paediatric Intensive Care Unit Labetalol Epoprostenol 
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  1. 1.
    Shirkey H. Therapeutic orphans. J Pediatr 1968; 72: 119–20PubMedCrossRefGoogle Scholar
  2. 2.
    Sutherland JM. Fatal cardiovascular collapse of infants receiving large amounts of chloramphenicol. Am J Dis Child 1959: 7Google Scholar
  3. 3.
    Weiss CF, Glazko AJ, Weston JK. Chloramphenicol in the newborn infant. N Engl J Med 1960; 262: 787–94PubMedCrossRefGoogle Scholar
  4. 4.
    Lenz W. Epidemiology of congenital malformations. Ann N Y Acad Sci 1965; 123: 228–36PubMedCrossRefGoogle Scholar
  5. 5.
    Choonara I, Dunne J. Licensing of medicines. Arch Dis Child 1998; 78: 402–3PubMedCrossRefGoogle Scholar
  6. 6.
    Turner S, Nunn AJ, Choonara I. Unlicensed drug use in children in the U.K. Paed Perinatal Drug Ther 1997; 1: 52–5Google Scholar
  7. 7.
    Turner S, Gill A, Nunn T, et al. Use of ‘off-label’and unlicensed drugs in paediatric intensive care unit. Lancet 1996; 347: 549–50PubMedCrossRefGoogle Scholar
  8. 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: 118–21PubMedCrossRefGoogle Scholar
  9. 9.
    Turner S, Longworth A, Nunn AJ, et al. Unlicensed drug use on paediatric wards. BMJ 1998; 316: 343–5PubMedCrossRefGoogle Scholar
  10. 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: 965–8PubMedCrossRefGoogle Scholar
  11. 11.
    Turner S. Unregistered and off-label drug use in paediatric inpatients. Aust J Hosp Pharm 1999; 29: 265–8Google Scholar
  12. 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: 79–82PubMedCrossRefGoogle Scholar
  13. 13.
    Conroy S, McIntyre J, Choonara I. Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed 1999; 80: F142–5PubMedCrossRefGoogle Scholar
  14. 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: S37–45PubMedCrossRefGoogle Scholar
  15. 15.
    McIntyre J, Conroy S, Avery A, et al. Unlicensed and off label prescribing of drugs in general practice. Arch Dis Child 2000; 83: 498–501PubMedCrossRefGoogle Scholar
  16. 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: 502–5PubMedCrossRefGoogle Scholar
  17. 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: 1125PubMedCrossRefGoogle Scholar
  18. 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: 15–8PubMedCrossRefGoogle Scholar
  19. 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: 77–83PubMedCrossRefGoogle Scholar
  20. 20.
    Gill AM, Leach HJ, Hughes J, et al. Adverse drug reactions in a paediatric intensive care unit. Acta Paediatr 1995; 84: 438–41PubMedCrossRefGoogle Scholar
  21. 21.
    Clarkson A, Ingleby E, Choonara I, et al. A novel scheme for the reporting of adverse drug reactions. Arch Dis Child 2001; 84: 337–9PubMedCrossRefGoogle Scholar
  22. 22.
    Hughes J, Leach HJ, Choonara I. Hallucinations on withdrawal of isoflurane used as sedation. Acta Paediatr 1993; 82: 885–6PubMedGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  1. 1.Academic Division of Child HealthUniversity of Nottingham, Derbyshire Children’s HospitalDerbyUK

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