Ricerca
Le priorità associate all’uso dei farmaci “off-label”
PRIORITIES AMONG OFF-LABEL PRESCRIPTIONS: PAEDIATRICIANS’ PERSPECTIVE
F. MARCHETTI1, J. BUA1, S. DEMARINI1, R. DEVESCOVI1, C. GERMANI1, P. MERGONI1, G. MESSI1, M. PENNESI1, M. RABUSIN1, A. SARTI1, A. VENTURA1; A. ARRIGHINI2, G. CHIRICO2, M. DUSE2, N. MIGLIETTI2, M.S. MOLINARO2, L.D. NOTARANGELO2, F. PORTA2, V. PORTERI2, E. SONCINI2, R.F. SCHUMACHER2; S. DI MAIO3, L. DI MARTINO3, L. GIORDANO3, F. DE LEVA3, C. PECORARO3; M. BALDI4, E. BANAUDI4, S. EINAUDI4, G. MIGLIORE4, P. PECCO4, P. SARACCO4, A. TOCCHET4; M. BONATI5
1Istituto per l'Infanzia “Burlo Garofolo”, Trieste (coordinamento);
2Ospedale dei Bambini, Brescia;
3AO Santobono - Pausilipon, Napoli;
4AO OIRM S. Anna, Torino;
5Laboratorio per la Salute Materno-Infantile, Istituto Mario Negri, Milano
Ottobre 2005 - pagg. 527 -531
Abstract
Two thirds of the drugs prescribed for children are off-label. However, off-label is not synonymous
with incorrect, since it often represents the most rational, evidence-based therapy.
Existing data on the use of off-label in children are based on prescriptions registers. The aim
of our study was to investigate the paediatricians’ perspective on off-label use in their everyday
hospital practice. Four Paediatrics Italian Hospitals were involved in the study. Questionnaires
covered eight different department/speciality units. Our findings showed that
the most common reasons detected for off-label use were formulation and age. Corticosteroids,
antihypertensive drugs and midazolam were most frequently indicated as off-label
for formulation, while ciprofloxacin, new generation anti-epilepsy drugs (lamotrigine, oxcarbazepine)
and immunosuppressant (mycophenolate, rituximab) for age. The drugs identified
as off-label differed according to department, although some recurred (i.e. ACE inhibitors,
ketorolac). Our survey might be of help for planning appropriate interventions to
tackle the problem of off-label use in paediatrics.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Bibliografia
1. Budetti PP. Ensuring safe and effective medications
for children. JAMA 2003;290(7):950-1.
2. Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr 2005;164(9):552-8.
3. Pandolfini C, Impicciatore P, Provasi D, et al. Off-label use of drugs in Italy: a prospective, observational and multicentre study. Acta Pediatr 2002;91:339-47.
4. Wilson JT. An update on the therapeutic orphan. Pediatrics 1999;104:585-90.
5. Smyth RL, Weindling AM. Research in children. Ethical and scientific aspects. Lancet 1999;354 (Suppl II):2124.
6. Steinbrook R. Testing medications in children. N Engl J Med 2002;347:1462-70.
7. Riordan FA. Use of unlabelled and off license drugs in children. Use of unlicensed drugs may be recommended in guidelines. BMJ 2000;320:1210.
8. Committee on Drugs. American Academy of Pediatrics. Uses of drugs not described in the package insert (off-label uses). Pediatrics 2002;110(1 Pt 1):181-3.
9. Hill P. Off licence and off label prescribing in children: litigation fears for physicians. Arch Dis Child 2005;90 Suppl 1:i17-8.
10. Nunn AJ. Making medicines that children can take. Arch Dis Child 2003;88(5):369-71.
11. Schirm E, Tobi H, de Vries TW, Choonara I, De Jong-van den Berg LT. Lack of appropriate formulation of medicines for children in the community. Acta Paediatr 2003;92(12): 1486-9.
12. Rocchi F, Raffaelli MP, Marelli G, Taddei GC, Bonati M. Gruppo di lavoro Ped-BG. Sorveglianza prospettica della produzione galenica di dosaggi pediatrici. Giornale italiano di Farmacia Clinica 2001;15:15-20.
13. Hilgers KF, Dotsch J, Rascher W, Mann JF. Treatment strategies in patients with chronic renal disease: ACE inhibitors, angiotensin receptor antagonists, or both? Pediatr Nephrol 2004;19(9):956-61.
14. Robinson RF, Nahata MC, Batisky DL, Mahan JD. Pharmacologic treatment of chronic pediatric hypertension. Paediatr Drugs 2005;7(1):27-40.
15. McIntyre J, Robertson S, Norris E, et al. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet 2005;366(9481):205-10.
16. Ministero della Salute. Guida all'uso dei farmaci per i bambini. Roma: Istituto Poligrafico e Zecca dello Stato, 2003.
17. O’Donnell CP, Stone RJ, Morley CJ. Unlicensed and off-label drug use in an Australian neonatal intensive care unit. Pediatrics 2002; 110(5):e52.
18. Richard DA, Nousia-Arvanitakis S, Sollich V, Hampel BJ, Sommerauer B, Schaad UB. Oral ciprofloxacin vs intravenous ceftazidime plus tobramycin in pediatric cystic fibrosis patients: comparison of anti-Pseudomonas efficacy and assessment of safety with ultrasonography and magnetic resonance imaging. Cystic Fibrosis Study Group. Pediatr Infect Dis J 1997;16(6):572-8.
19. Hoiby N, Frederiksen B, Pressler T. Eradication of early Pseudomonas aeruginosa infection. J Cyst Fibros 2005; Suppl 2:49-54.
20. Gendrel D, Chalumeau M, Moulin F, Raymond J. Fluoroquinolones in paediatrics: a risk for the patient or for the community? Lancet Infect Dis 2003;3(9):537-46.
21. Barbi E, Gerarduzzi T, Marchetti F, et al. Deep sedation with propofol by nonanesthesiologists: a prospective pediatric experience. Arch Pediatr Adolesc Med 2003;157(11):1097- 103.
22. Wheeler DS, Vaux KK, Ponaman ML, Poss BW. The safe and effective use of propofol sedation in children undergoing diagnostic and therapeutic procedures: experience in a pediatric ICU and a review of the literature. Pediatr Emerg Care 2003;19(6):385-92.
23. Beghi E. Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines. Lancet Neurol 2004;3(10): 618-21.
24. Bonati M, Choonara I, Hoppu K, Pons G, Seyberth H. Closing the gap in drug therapy. Lancet 1999;353(9164):1625.
25. Proposta di regolamentazione del Parlamento e del Consiglio relative ai farmaci utilizzati in pediatria, che modifica il regolamento (CEE) n° 1768/92, la direttiva 2001/83 CE e il regolamento CE n° 724/2004 (http:/pharmacos. eudra.org/F2/Paediatrics/index.htm)
26. Roberts R, Rodriguez W, Murphy D, Crescenzi T. Pediatric drug labelling. Improving the safety and efficacy of pediatric therapies. JAMA 2003;290:905-11.
27. Redazionale. Il regolamento europeo per i farmaci “pediatrici” non risponde ai bisogni dei bambini. Quaderni acp 2005;12(4):172.
2. Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr 2005;164(9):552-8.
3. Pandolfini C, Impicciatore P, Provasi D, et al. Off-label use of drugs in Italy: a prospective, observational and multicentre study. Acta Pediatr 2002;91:339-47.
4. Wilson JT. An update on the therapeutic orphan. Pediatrics 1999;104:585-90.
5. Smyth RL, Weindling AM. Research in children. Ethical and scientific aspects. Lancet 1999;354 (Suppl II):2124.
6. Steinbrook R. Testing medications in children. N Engl J Med 2002;347:1462-70.
7. Riordan FA. Use of unlabelled and off license drugs in children. Use of unlicensed drugs may be recommended in guidelines. BMJ 2000;320:1210.
8. Committee on Drugs. American Academy of Pediatrics. Uses of drugs not described in the package insert (off-label uses). Pediatrics 2002;110(1 Pt 1):181-3.
9. Hill P. Off licence and off label prescribing in children: litigation fears for physicians. Arch Dis Child 2005;90 Suppl 1:i17-8.
10. Nunn AJ. Making medicines that children can take. Arch Dis Child 2003;88(5):369-71.
11. Schirm E, Tobi H, de Vries TW, Choonara I, De Jong-van den Berg LT. Lack of appropriate formulation of medicines for children in the community. Acta Paediatr 2003;92(12): 1486-9.
12. Rocchi F, Raffaelli MP, Marelli G, Taddei GC, Bonati M. Gruppo di lavoro Ped-BG. Sorveglianza prospettica della produzione galenica di dosaggi pediatrici. Giornale italiano di Farmacia Clinica 2001;15:15-20.
13. Hilgers KF, Dotsch J, Rascher W, Mann JF. Treatment strategies in patients with chronic renal disease: ACE inhibitors, angiotensin receptor antagonists, or both? Pediatr Nephrol 2004;19(9):956-61.
14. Robinson RF, Nahata MC, Batisky DL, Mahan JD. Pharmacologic treatment of chronic pediatric hypertension. Paediatr Drugs 2005;7(1):27-40.
15. McIntyre J, Robertson S, Norris E, et al. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet 2005;366(9481):205-10.
16. Ministero della Salute. Guida all'uso dei farmaci per i bambini. Roma: Istituto Poligrafico e Zecca dello Stato, 2003.
17. O’Donnell CP, Stone RJ, Morley CJ. Unlicensed and off-label drug use in an Australian neonatal intensive care unit. Pediatrics 2002; 110(5):e52.
18. Richard DA, Nousia-Arvanitakis S, Sollich V, Hampel BJ, Sommerauer B, Schaad UB. Oral ciprofloxacin vs intravenous ceftazidime plus tobramycin in pediatric cystic fibrosis patients: comparison of anti-Pseudomonas efficacy and assessment of safety with ultrasonography and magnetic resonance imaging. Cystic Fibrosis Study Group. Pediatr Infect Dis J 1997;16(6):572-8.
19. Hoiby N, Frederiksen B, Pressler T. Eradication of early Pseudomonas aeruginosa infection. J Cyst Fibros 2005; Suppl 2:49-54.
20. Gendrel D, Chalumeau M, Moulin F, Raymond J. Fluoroquinolones in paediatrics: a risk for the patient or for the community? Lancet Infect Dis 2003;3(9):537-46.
21. Barbi E, Gerarduzzi T, Marchetti F, et al. Deep sedation with propofol by nonanesthesiologists: a prospective pediatric experience. Arch Pediatr Adolesc Med 2003;157(11):1097- 103.
22. Wheeler DS, Vaux KK, Ponaman ML, Poss BW. The safe and effective use of propofol sedation in children undergoing diagnostic and therapeutic procedures: experience in a pediatric ICU and a review of the literature. Pediatr Emerg Care 2003;19(6):385-92.
23. Beghi E. Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines. Lancet Neurol 2004;3(10): 618-21.
24. Bonati M, Choonara I, Hoppu K, Pons G, Seyberth H. Closing the gap in drug therapy. Lancet 1999;353(9164):1625.
25. Proposta di regolamentazione del Parlamento e del Consiglio relative ai farmaci utilizzati in pediatria, che modifica il regolamento (CEE) n° 1768/92, la direttiva 2001/83 CE e il regolamento CE n° 724/2004 (http:/pharmacos. eudra.org/F2/Paediatrics/index.htm)
26. Roberts R, Rodriguez W, Murphy D, Crescenzi T. Pediatric drug labelling. Improving the safety and efficacy of pediatric therapies. JAMA 2003;290:905-11.
27. Redazionale. Il regolamento europeo per i farmaci “pediatrici” non risponde ai bisogni dei bambini. Quaderni acp 2005;12(4):172.
Corrispondenza: marchetti@burlo.trieste.