OFF-LABEL AND UNLICENSED PRESCRIBING IN PEDIATRIC INPATIENTS WITH NEPHROTIC SYNDROME IN A MAJOR TEACHING HOSPITAL: AN INDONESIAN CONTEXT
Objective: To estimate the prevalence of off-label and unlicensed prescribing in pediatric inpatients with nephrotic syndrome in a major teaching hospital in Indonesia.
Methods: A retrospective study was conducted in study hospital using medical records from pediatric inpatients with nephrotic syndrome during the period of January-December 2015. Patient and prescribing data were collected, and drugs were classified as on-label or off-label/unlicensed based on the Indonesia National Drug Information (IONI). Thereafter, off-label drugs were categorized with a hierarchical system of age, indication, route of administration, and dosage.
Results: There were 1553 drugs with 94 different types of drug administered to 67 patients during the study period. The data uncovered that1023 Â (65.9%) Â of Â the Â drug Â prescriptions Â were Â used Â either Â off-label/unlicensed. Â Most Â off-label Â drugs Â (n=433, Â 42.4%) Â were Â from Â nondiureticsantihypertensive drugs. The most common drugs used in an off-label/unlicensed manner were prednisolone and lisinopril. The high rate of off-label drug use in children was mainly related to age (n=772, 75.5%). Pediatrics with nephrotic syndrome was vulnerable to off-label uses where every patient received at least two off-label drugs. It seems that off-label prescribing in pediatric with nephrotic syndrome was not influenced by age or gender as every patient received off-label drugs.
Conclusion: Despite the high prevalence of off-label use in pediatric patients with nephrotic syndrome, this use is supported by evidence-based prescribing. Further, there remains a need for supporting clinical trials for pediatric drugs and updating IONI as the standard drug information in Indonesia to provide complete product information for pediatric use.
Keywords: Off-label drug, Syndrome nephrotic, Inpatient, Pediatrics.
The American Academy of Pediatrics. Policy statement: Off-label use of drugs in children. Pediatrics 2014;133:563-7.
Turner S, Longworth A, Nunn AJ, Choonara I. Unlicensed and off label drug use in paediatric wards: Prospective study. BMJ (7128):343-5.
â€˜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
Sinha Y, Cranswick NE. How to use medicines in children: Principles of paediatric clinical pharmacology. J Paediatr Child Health 2007;43(3):107-11.
Shirkey H. Therapeutic orphans. J Pediatr 1968;72(1):119-20.
Czarniak P, Bint L, FaviÃ© L, Parsons R, Hughes J, Sunderland B. Clinical setting influences off-label and unlicensed prescribing in a paediatric teaching hospital. PLoS One 2015;10(3):e0120630.
Oâ€™Donnell CP, Stone RJ, Morley CJ. Unlicensed and off-label drug use in an Australian neonatal intensive care unit. Pediatrics 2002;110(5):e52.
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(3):277-87.
Yasinta M, Che RC, Hu CY, Du XH, Ding GX, Huang SM. Use of off-label nephrology-related drugs in hospitalized pediatric patients: A retrospective study. World J Pediatr 2016;12(2):236-42.
European Medicines Agency. ICH Topic E11 Clinical Investigation of Medicinal Products in the Paediatric Population; 2001. Available from: http://www.ema.europa.edu/docs/en_GB/document_library/Scientific_ guideline/2009/09/WC500002926.pdf.
Badan Pengawasan Obat dan Makanan. Informatorium Obat Nasional Indonesia. Jakarta: Badan Pengawasan Obat dan Makanan; 2015. Available from: http://www.pionas.pom.go.id/ioni.
Hsien L, Breddemann A, Frobel AK, Heusch A, Schmidt KG, LÃ¤er S. Off-label drug use among hospitalised children: Identifying areas with the highest need for research. Pharm World Sci 2008;30(5):497-502.
Di Paolo ER, Stoetter H, Cotting J, Frey P, Gehri M, Beck-Popovic M, et al. Unlicensed and off-label drug use in a Swiss paediatric university hospital. Swiss Med Wkly 2006;136(13-14):218-22.
Lee JL, Redzuan AM, Shah NM. Unlicensed and off-label use of medicines in children admitted to the intensive care units of a hospital in Malaysia. Int J Clin Pharm 2013;35(6):1025-9.
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. BMJ 2000 8;320(7227):79-82.
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(2):143-7.
Barr J, Brenner-Zada G, Heiman E, Pareth G, Bulkowstein M, Greenberg R, et al. Unlicensed and off-label medication use in a neonatal intensive care unit: A prospective study. Am J Perinatol 2002;19(2):67-72.
Conroy S, McIntyre J, Choonara I. Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed 1999;80(2):F142-4.
Palcevski G, SkocibuÅ¡ic N, Vlahovic-Palcevski V. Unlicensed and off- label drug use in hospitalized children in Croatia: A cross-sectional survey. Eur J Clin Pharmacol 2012;68(7):1073-7.
Gavrilov V, Lifshitz M, Levy J, Gorodischer R. Unlicensed and off- label medication use in a general pediatrics ambulatory hospital unit in Israel. Isr Med Assoc J 2000;2(8):595-7.
Lombel RM, Gipson DS, Hodson EM; Kidney Disease: Improving Global Outcomes. Treatment of steroid-sensitive nephrotic syndrome: New guidelines from KDIGO. Pediatr Nephrol 2013;28(3):415-26.
Rheault MN, Zhang L, Selewski DT, Kallash M, Tran CL, Seamon M, et al. AKI in Children Hospitalized with Nephrotic Syndrome. Clin J Am Soc Nephrol 2015;10(1):2110-8.
Prescott WA Jr, Streetman DA, Streetman DS. The potential role of HMG-CoA reductase inhibitors in pediatric nephrotic syndrome. Ann Pharmacother 2004;38(12):2105-14.
Zaffanello M, Franchini M. Thromboembolism in childhood nephrotic syndrome: A rare but serious complication. Hematology 2007(1);12:69-73.
Hattingh L. Guidelines for off-label medicine use. Aust Pharm 2014;30:70-1.
Brion F, Nunn AJ, Rieutord A. Extemporaneous (magistral) preparation of oral medicines for children in European hospitals. Acta Paediatr 2003;92(4):486-90.
Kimland E, Odlind V. Off-label drug use in pediatric patients. Clin Pharmacol Ther 2012;91(5):796-801.
Lass J, Irs A, Pisarev H, Leinemann T, Lutsar I. Off label use of prescription medicines in children in outpatient setting in Estonia is common. Pharmacoepidemiol Drug Saf 2011;20:474-81.
European Medicines Agency. Medicines for children; 2006. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/ regulation/document_listing/document_listing_000068. jsp&mid=WC0b01ac058002 5b8b.
The United States Congress. Pediatric Research Equity Act 2003; (S.650). Available from: http://www.govtrack.us/congress/ bills/108/s650.
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