The peculiarities of off-label use of drugs in pediatrics
DOI:
https://doi.org/10.14739/2310-1210.2020.5.214751Keywords:
pediatrics, pharmacotherapy, off-label useAbstract
Prescribing drugs is not an easy task for pediatricians since the range of choice of drugs in pediatrics is 2/3 less than in adult patients.
The aim of this work is to analyze the literature data on the experience of using off-label drugs in pediatrics in the world.
Materials and methods. Bibliographic analysis, literature review, statistical analysis.
Results. Based on the analysis, it was found that one of the most important reasons for off-label drug prescribing in children is the lack of standard, licensed, and safe therapeutic options for clinical trials of drugs in some diseases or conditions in children. Possible approaches to solving problems of “off-lable use” of drugs in medicine and health care are presented.
Conclusions. Off-label drug use in children can be improved by reports from pediatricians of pediatric experience with various off-label drugs in the form of scientific articles or discussions at scientific conferences, or with high levels of evidence. When deciding on the prescription of an off-label drug to a child, doctors should be sure that this is the only correct step, provided that there is a national form and a national list of essential medicines.
References
Gillick, M. R. (2009). Controlling Off-Label Medication Use. Annals of Internal Medicine, 150(5), 344-347. https://doi.org/10.7326/0003-4819-150-5-200903030-00108
Laughon, M. M., Benjamin, D. K., Jr, Capparelli, E. V., Kearns, G.L., Berezny, K., Paul, I. M., Wade, K., Barrett, J., Smith, P. B., & Cohen-Wolkowiez, M. (2011). Innovative clinical trial design for pediatric therapeutics. Expert Review of Clinical Pharmacology, 4(5), 643-652. https://doi.org/10.1586/ecp.11.43
Lukianchuk, J. O. (2018). Side effects of off label drugs. Topical issues of new drugs development. Abstracts оf XXV International Scientific And Practical Conference Of Young Scientists And Student (pp. 267). NUPh.
Guidi, B., & Nocco, L. (2011). The debate concerning the off-label prescriptions of drugs: a comparison between Italian and U.S. law. Opinio Juris in Comparatione, 1(1). http://www.opiniojurisincomparatione.org/opinio/article/view/43
Fabiano, V., Mameli, C., & Zuccotti, G. V. (2012). Adverse drug reactions in newborns, infants and toddlers: pediatric pharmacovigilance between present and future. Expert Opinion on Drug Safety, 11(1), 95-105. https://doi.org/10.1517/14740338.2011.584531
Komarova, A. P. (2017). Off-label use of drugs in children. Topical issues of new drugs development. Abstracts оf XXIV International Scientific And Practical Conference Of Young Scientists And Student (Vol. 2, pp. 50-51). NUPh.
Jain, S. S., Bavdekar, S. B., Gogtay, N. J., & Sadawarte, P. A. (2008). Off-label drug use in children. Indian Journal of Pediatrics, 75, Article 1133. https://doi.org/10.1007/s12098-008-0188-1
Lee, J. H., Byon, H. J., Choi, S., Jang, Y. E., Kim, E. H., Kim, J. T., & Kim, H. S. (2018). Safety and Efficacy of Off-label and Unlicensed Medicines in Children. Journal of Korean Medical Science, 33(37), Article e227. https://doi.org/10.3346/jkms.2018.33.e227
Allen, H. C., Garbe, M. C., Lees, J., Aziz, N., Chaaban, H., Miller, J. L., Johnson, P., & DeLeon, S. (2018). Off-Label Medication use in Children, More Common than We Think: A Systematic Review of the Literature. Journal of the Oklahoma State Medical Association, 111(8), 776-783.
Shah, S. S., Hall, M., Goodman, D. M., Feuer, P., Sharma, V., Fargason, C., Jr, Hyman, D., Jenkins, K., White, M. L., Levy, F. H., Levin, J. E., Bertoch, D., & Slonim, A. D. (2007). Off-label drug use in hospitalized children. Archives of Pediatrics & Adolescent Medicine, 161(3), 282-290. https://doi.org/10.1001/archpedi.161.3.282
Frattarelli, D. A., Galinkin, J. L., Green, T. P., Johnson, T. D., Neville, K. A., Paul, I. M., Van Den Anker, J. N., & American Academy of Pediatrics Committee on Drugs. (2014). Off-label use of drugs in children. Pediatrics, 133(3), 563-567. https://doi.org/10.1542/peds.2013-4060
Yackey, K., Stukus, K., Cohen, D., Kline, D., Zhao, S., & Stanley, R. (2019). Off-label Medication Prescribing Patterns in Pediatrics: An Update. Hospital Pediatrics, 9(3), 186-193. https://doi.org/10.1542/hpeds.2018-0168
Palčevski, G., Skočibušić, N., & Vlahović-Palčevski, V. (2012). Unlicensed and off-label drug use in hospitalized children in Croatia: a cross-sectional survey. European Journal of Clinical Pharmacology, 68(7), 1073-1077. https://doi.org/10.1007/s00228-012-1221-x
Rogers, J. (2008). Freedom of Speech and the FDA’s Regulation of Off-Label Drug Uses. The George Washington Law Review, 76(5), 1429-1443. http://www.gwlr.org/wp-content/uploads/2012/08/76-5-Rogers.pdf
Stafford, R. S. (2008). Regulating Off-Label Drug Use - Rethinking the Role of the FDA. The New England Journal of Medicine, 358(14), 1427-1429. https://doi.org/10.1056/NEJMp0802107
Yackey, K., & Stanley, R. (2019). Off-Label Prescribing in Children Remains High: A Call for Prioritized Research. Pediatrics, 144(4), Article e20191571. https://doi.org/10.1542/peds.2019-1571
Czaja, A. S., Reiter, P. D., Schultz, M. L., & Valuck, R. J. (2015). Patterns of Off-Label Prescribing in the Pediatric Intensive Care Unit and Prioritizing Future Research. The Journal of Pediatric Pharmacology and Therapeutics, 20(3), 186-196. https://doi.org/10.5863/1551-6776-20.3.186
Palmaro, A., Bissuel, R., Renaud, N., Durrieu, G., Escourrou, B., Oustric, S., Montastruc, J. L., & Lapeyre-Mestre, M. (2015). Off-label prescribing in pediatric outpatients. Pediatrics, 135(1), 49-58. https://doi.org/10.1542/peds.2014-0764
Aagaard, L. (2015). Off-Label and Unlicensed Prescribing of Medicines in Paediatric Populations: Occurrence and Safety Aspects. Basic & Clinical Pharmacology & Toxicology, 117(4), 215-218. https://doi.org/10.1111/bcpt.12445
Teigen, A., Wang, S., Truong, B. T., & Bjerknes, K. (2017). Off-label and unlicensed medicines to hospitalised children in Norway. The Journal of Pharmacy and Pharmacology, 69(4), 432-438. https://doi.org/10.1111/jphp.12581
Tefera, Y. G., Gebresillassie, B. M., Mekuria, A. B., Abebe, T. B., Erku, D. A., Seid, N., & Beshir, H. B. (2017). Off-label drug use in hospitalized children: a prospective observational study at Gondar University Referral Hospital, Northwestern Ethiopia. Pharmacology Research & Perspectives, 5(2), Article e00304. https://doi.org/10.1002/prp2.304
Mühlbauer, B., Janhsen, K., Pichler, J., & Schoettler, P. (2009). Off-label use of prescription drugs in childhood and adolescence: an analysis of prescription patterns in Germany. Deutsches Arzteblatt International, 106(3), 25-31. https://doi.org/10.3238/arztebl.2009.0025
Landwehr, C., Richardson, J., Bint, L., Parsons, R., Sunderland, B., & Czarniak, P. (2019). Cross-sectional survey of off-label and unlicensed prescribing for inpatients at a paediatric teaching hospital in Western Australia. PLOS ONE, 14(1), Article e0210237. https://doi.org/10.1371/journal.pone.0210237
Panther, S. G., Knotts, A. M., Odom-Maryon, T., Daratha, K., Woo, T., & Klein, T. A. (2017). Off-label Prescribing Trends for ADHD Medications in Very Young Children. The Journal of Pediatric Pharmacology and Therapeutics, 22(6), 423-429. https://doi.org/10.5863/1551-6776-22.6.423
Mulligan, E., & Messenger, H. (2011). Mifepristone in South Australia - the first 1343 tablets. Australian Family Physician, 40(5), 342-352.
Kimland, E., & Odlind, V. (2012). Off-label drug use in pediatric patients. Clinical Pharmacology & Therapeutics, 91(5), 796-801. https://doi.org/10.1038/clpt.2012.26
Roberts, G., Xatzipsalti, M., Borrego, L. M., Custovic, A., Halken, S., Hellings, P. W., Papadopoulos, N. G., Rotiroti, G., Scadding, G., Timmermans, F., & Valovirta, E. (2013). Paediatric rhinitis: position paper of the European Academy of Allergy and Clinical Immunology. Allergy, 68(9), 1102-1116. https://doi.org/10.1111/all.12235
Sturkenboom, M. C., Verhamme, K. M., Nicolosi, A., Murray, M. L., Neubert, A., Caudri, D., Picelli, G., Sen, E. F., Giaquinto, C., Cantarutti, L., Baiardi, P., Felisi, M. G., Ceci, A., Wong, I. C., & TEDDY European Network of Excellence. (2008). Drug use in children: cohort study in three European countries. British Medical Journal, 337, Article a2245. https://doi.org/10.1136/bmj.a2245
Tsygankova, O. V., Batluk, T. I., Latyntseva, L. D., Platonov, D. Y., & Akhmedzhanov, N. M. (2019). Yuridicheskie i meditsinskie aspekty naznacheniya lekarstvennykh sredstv vne instruktsii. Tochka zreniya [Legal and Medical Aspects of Off-Label Medication Use. Point of View]. Ratsional'naya Farmakoterapiya v Kardiologii, 15(1), 130-134. https://doi.org/10.20996/1819-6446-2019-15-1-130-134 [in Russian].
Mustafina-Bredikhina, D. M. (2015). Primenenie lekarstvennykh preparatov off-label: mezhdunarodnyi opyt i perspektivy v Rossii [Off-label prescription drugs use: international practice and perspectives on Russia]. Neonatologiya: novosti, mneniya, obuchenie, (1), 77-79. [in Russian].
Molyneux, C. G., & Bogaert, P. (2010, 25 October). The need for informed consent in off label use in the EU. Pharma Intelligence. https://pink.pharmaintelligence.informa.com/PS115666/The-need-for-informed-consent-in-offlabel-use-in-the-EU
Mason, J., Pirmohamed, M., & Nunn, T. (2012). Off-label and unlicensed medicine use and adverse drug reactions in children: a narrative review of the literature. European Journal of Clinical Pharmacology, 68(1), 21-28. https://doi.org/10.1007/s00228-011-1097-1
Czarniak, P., Bint, L., Favié, L., Parsons, R., Hughes, J., & Sunderland, B. (2015). Clinical Setting Influences Off-Label and Unlicensed Prescribing in a Paediatric Teaching Hospital. PLOS ONE, 10(3), Article e0120630. https://doi.org/10.1371/journal.pone.0120630
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)