International Journal of Clinical Pharmacy

, Volume 33, Issue 4, pp 650–655 | Cite as

Extent and nature of unlicensed and off-label medicine use in hospitalised children in Palestine

  • Maher R. Khdour
  • Hussein Othman Hallak
  • Kawther Shab’an Atallah Alayasa
  • Qusai Nabeel AlShahed
  • Ahmed F. Hawwa
  • James C. McElnayEmail author
Research Article


Objective of the study To determine the extent and nature of unlicensed/off-label prescribing patterns in hospitalised children in Palestine. Setting Four paediatric wards in two public health system hospitals in Palestine [Caritas children’s hospital (Medical and neonatal intensive care units) and Rafidia general hospital (Medical and surgical units)]. Method A prospective survey of drugs administered to infants and children <18 years old was carried out over a five-week period in the four paediatric wards. Main outcome measure Drug-licensing status of all prescriptions was determined according to the Palestinian Registered Product List and the Physician’s Desk Reference. Results Overall, 917 drug prescriptions were administered to 387children. Of all drug prescriptions, 528 (57.5%) were licensed for use in children; 65 (7.1%) were unlicensed; and 324 (35.3%) were used off-label. Of all children, 49.6% received off-label prescriptions, 10.1% received unlicensed medications and 8.2% received both. Seventy-two percent of off-label drugs and 66% of unlicensed drugs were prescribed for children <2 years. Multivariate analysis showed that patients who were admitted to the neonatal intensive care unit and infants aged 0–1 years were most likely to receive a greater number of off-label or unlicensed medications (OR 1.80; 95% CI 1.03–3.59 and OR 1.99; 95% CI 0.88–3.73, respectively). Conclusion The present findings confirmed the elevated prevalence of unlicensed and off-label paediatric drugs use in Palestine and strongly support the need to perform well designed clinical studies in children.


Neonates Off-label prescribing Paediatrics Palestine Unlicensed medicines Ward 



The authors wish to thank Dr Chris Cardwell, Department of Epidemiology and Public Health, Queen’s University Belfast, for his statistical support, Nursing & administrative staff at the Caritas and Rafidia hospitals.


The Daniel Turnberg UK/Middle East Travel Fellowship for financial support is acknowledged.

Conflicts of interest

None to declare.


  1. 1.
    Kearns GL, Abdel‐Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology‐drug disposition, action, therapy in infants and children. N Engl J Med. 2003;349:1157–67.PubMedCrossRefGoogle Scholar
  2. 2.
    Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane A, et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. European Network for Drug Investigation in Children. Br Med J. 2000;320:79–82.CrossRefGoogle Scholar
  3. 3.
    ‘t Jong GW, van der Linden PD, Bakker EM, van der Lely N, Eland IA, Stricker BH, et al. Unlicensed and off‐label drug use in a paediatric ward of a general hospital in the Netherlands. Eur J Clin Pharmacol. 2002;58:293–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Dell’Aera M, Gasbarro AR, Padovano M, Laforgia N, Capodiferro D, Solarino B, et al. Unlicensed and off‐label use of medicines at a neonatology clinic in Italy. Pharm World Sci. 2007;29:361–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Shah SS, Hall M, Goodman DM, Feuer P, Sharma V, Fargason C, et al. Off‐label drug use in hospitalized children. Arch Pediatr Adolesc Med. 2007;161:282–90.PubMedCrossRefGoogle Scholar
  6. 6.
    Turner S, Nunn AJ, Fielding K, Choonara I. Adverse drug reactions to unlicensed and off‐label drugs on paediatric wards: a prospective study. Acta Paediatr. 1999;88:965–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Turner S, Nunn AJ, Choonara I. Unlicensed drug use in children in the UK. Paediatr Perinat Drug Ther. 1997;1:52–5.Google Scholar
  8. 8.
    McIntyre J, Conroy S, Avery A, Corns H, Choonara I. Unlicensed and off label prescribing of drugs in general practice. Arch Dis Child. 2000;83:498–501.PubMedCrossRefGoogle Scholar
  9. 9.
    Royal College of Paediatrics and Child Health. The use of unlicensed medicines or licensed medicines for unlicensed applications in paediatric practice [Internet]. London: Royal College of Paediatrics and Child Health; 2002 [cited 2011 Jan 21]. Available from:
  10. 10.
    Mukattash T, Hawwa AF, Trew K, McElnay JC. Healthcare professional experiences and attitudes on unlicensed/off-label paediatric prescribing and paediatric clinical trials. Eur J Clin Pharmacol. 2011 [forthcoming].Google Scholar
  11. 11.
    Cuzzolin L, Atzei A, Fanos V. Off‐label and unlicensed prescribing for newborns and children in different settings: a review of the literature and a consideration about drug safety. Expert Opin Drug Saf. 2006;5:703–18.PubMedCrossRefGoogle Scholar
  12. 12.
    Lindell-Osuagwu L, Korhonen MJ, Saano S, Helin-Tanninen M, Naaranlahti T, Kokki H. Off-label and unlicensed drug prescribing in three paediatric wards in Finland and review of the international literature. J Clin Pharm Ther. 2009;34:277–87.PubMedCrossRefGoogle Scholar
  13. 13.
    Santos DB, Coelho LL, Clavenna AM. Off‐label and unlicensed drug utilization in hospitalized children in Fortaleza, Brazil. Eur J Clin Pharmacol. 2008;64:1111–8.PubMedCrossRefGoogle Scholar
  14. 14.
    State of Palestine Ministry of Health. Palestinian essential drug list [Internet]. Nablus: Ministry of Health; 2006 [cited 2011 Jan 21]. Available from:
  15. 15.
    Sifton DW. editor. Physicians’ Desk Reference. 62nd ed. Montvale: Medical Economics Company; 2008.Google Scholar
  16. 16.
    World Health Organization. The International statistical classification of diseases and related health problems (ICD), 10th Revision [Internet]. Geneva: WHO & DIMDI; 2006 [updated 2007; cited 2011 Jan 21]. Available from:
  17. 17.
    Avenel S, Bomkratz A, Dassieu G, Janaud JC, Danan C. The incidence of prescriptions without marketing product license in a neonatal intensive care unit. Arch Pediatr. 2000;7:143–7.PubMedCrossRefGoogle Scholar
  18. 18.
    ‘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
  19. 19.
    ‘t Jong GW, Vulto AG, de Hoog M, Schimmel KJ, Tibboel D, van den Anker JN. Unapproved, off‐label use of drugs in a children’s hospital. N Engl J Med. 2000;343:1125.PubMedCrossRefGoogle Scholar
  20. 20.
    O’Donnell CP, Stone RJ, Morley CJ. Unlicensed and off‐label drug use in an Australian neonatal intensive care unit. Pediatrics. 2002;110:e52.PubMedCrossRefGoogle Scholar
  21. 21.
    Carvalho PR, Carvalho CG, Alievi PT, Martinbiancho J, Trotta EA. Prescription of drugs not appropriate for children in a pediatric intensive care unit. Jornal de Pediatria. 2003;79:397–402.PubMedGoogle Scholar
  22. 22.
    Neubert A, Lukas K, Leis T, Dormann H, Brune K, Rascher W. Drug utilisation on a preterm and neonatal intensive care unit in Germany: a prospective, cohort-based analysis. Eur J Clin Pharmacol. 2010;66:87–95.PubMedCrossRefGoogle Scholar
  23. 23.
    Conroy S, McIntyre J, Choonara I. Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed. 1999 Mar;80(2):F142–4; discussion F144–5.Google Scholar
  24. 24.
    Phan H, Leder M, Fishley M, Moeller M, Nahata M. Off-label and unlicensed medication use and associated adverse drug events in a pediatric emergency department. Pediatr Emerg Care. 2010;26:424–30.PubMedCrossRefGoogle Scholar
  25. 25.
    Di Paolo ER, Stoetter H, Cotting J, Frey P, Gehri M, Beck‐Popovic M, et al. Unlicensed and offlabel drug use in a Swiss paediatric university hospital. Swiss Med Wkly. 2006;136:218–22.PubMedGoogle Scholar
  26. 26.
    Chalumeau M, Treluyer JM, Salanave B, Brayley S, Thomson MB. Off label and unlicensed drug use among French office based paediatricians. Arch Dis Child. 2000;83:502–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Dick A, Keady S, Mohammad F, Brayley S, Thomson M, Lloyd BW, et al. Use of unlicensed and off‐label medications in paediatric gastroenterology with a review of the commonly used formularies in the UK. Aliment Pharmacol Ther. 2003;17:571–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Sawalha A. Self‐medication with antibiotics: a study in Palestine. Int J Risk Saf Med. 2008;20:213–22.Google Scholar
  29. 29.
    Khatib R, Gaicaman R. Treatment of infection: across sectional surveyof antibiotic drug utilization in the Ramallah district of Palestine. Int J Pharm Pract. 2006;14:211–7.CrossRefGoogle Scholar
  30. 30.
    Pandolfini C, Bonati M. A literature review on off‐label drug use in children. Eur J Pediatr. 2005;164:552–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Nascimento‐Carvalho CM, Souza‐Marques HH. Recommendation of the Brazilian society of pediatrics for antibiotic therapy in children and adolescents with community‐acquired pneumonia. Rev Panam Salud Publica. 2004;15:380–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Mulla H, Tofeig M, Bu’Lock F, Samani N, Pandya HC. Variations in captopril formulations used to treat children with heart failure: a survey in the United Kingdom. Arch Dis Child. 2007;92:409–11.PubMedCrossRefGoogle Scholar
  33. 33.
    Conroy S. Extemporaneous (magistral) preparations of oral medicines for children in European hospitals. Acta Paediatr. 2003;92:408–41.PubMedCrossRefGoogle Scholar
  34. 34.
    Benini F, Johnston C, Faucher D, Aranda JV. Topical anesthesia during circumcision in newborn infants. JAMA. 1993;270:850–3.PubMedCrossRefGoogle Scholar
  35. 35.
    Parkinson L, Hughes J, Gill A, Billingham I, Ratcliffe J, Choonara I. A randomised controlled trial of sedation in the critically ill. Pediatr Anesth. 1997;7:405–10.CrossRefGoogle Scholar
  36. 36.
    Nahata MC. Licensing of medicines for children in the USA. Paediatr Perinat Drug Ther. 1997;1:50–1.Google Scholar
  37. 37.
    Kauffman RE. Status of drug approval processes and regulation of medi‐ cations for children. Curr Opinion Pediatr. 1995;7:195–8.PubMedCrossRefGoogle Scholar
  38. 38.
    The European agency for the evaluation of medicinal products (EMEA). Medicines for children: the paediatric regulation [Internet]. Strasbourg: EMEA; 2006 [cited 2011 Jan 21]. Available from:‐1/reg_2006_1901/reg_2006_1901_en.pdf.

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Maher R. Khdour
    • 1
  • Hussein Othman Hallak
    • 1
  • Kawther Shab’an Atallah Alayasa
    • 2
  • Qusai Nabeel AlShahed
    • 3
  • Ahmed F. Hawwa
    • 4
  • James C. McElnay
    • 4
    Email author
  1. 1.Faculty of PharmacyAl-Quds UniversityAbu-Dies, JerusalemPalestine
  2. 2.Faculty of NursingAl-Quds UniversityAbu-Dies, JerusalemPalestine
  3. 3.Department of PharmacyPatient Friends Society/Al-Rahma PolyClinic, NablusNablusPalestine
  4. 4.Clinical and Practice Research Group, School of Pharmacy, Medical Biology CentreQueen’s University BelfastBelfastUK

Personalised recommendations