The Russian study of «off-label» drug use in pediatric practice: 2015 vs 2012

Purpose. To study and compare the structure of off-label drug use in children in 2012 and 2015 by means of analysis of the national pharmacovigilance database. Materials and methods. We conducted a comparative analysis of 341 spontaneous reports about serious adverse reactions in children, submitted to the Russian pharmacovigilance database in 2012, and 467 suchlike spontaneous reports registered in 2015. Approved in the Russian Federation prescribing drug information was used to identify «off label» drug use. Results. It was established that 58,7% of suspected medicines in 2012 and 47,5% in 2015, the use of which was associated with the development of serious complications in pharmacotherapy in children, were prescribed with deviations from the recommendations of approved prescribing drug information. Systemic antimicrobial agents and drugs for the treatment of nervous system diseases were the most common groups of drugs prescribed off-label in pediatric practice. The main types of off-label violations were inappropriate indications, deviations from the recommended dosage regimen and the use of a drug in the age group of patients, wherein the drug has not been approved. Conclusion. Our research confirms, that the practice of off-label drug use in children is not safe. It is shown that spontaneous reporting is an effective method of study the problems of drug safety in children.

дети, лекарственные препараты, «off-label» назначения, спонтанные сообщения, фармаконадзор, children, drugs, «off label» drug use, spontaneous reports, pharmacovigilance

1. Василевский И.В. Клиническая фармакология и педиатрическая практика. Медицинские новости, 2014; 11 (242): 6-12.

2. Тополянская С.В. Общие методологические проблемы проведения клинических исследований у детей. Педиатрическая фармакология. 2010; 75: 6-10.

3. Blake K.V., Zaccaria C., Domergue F., La Mache E., Saint-Raymond A., Hidalgo-Simon A. Comparison between paediatric and adult suspected adverse drug reactions reported to the European medicines agency: implications for pharmacovigilance. Paediatr Drugs. 2014 Aug; 16 (4): 309-19.

4. Зырянов С.К., Белоусов Ю.Б. Использование лекарств в педиатрии: есть ли проблемы? Медицинские технологии. Оценка и выбор. 2011; 2: 37-41.

5. Решение совета Евразийской экономической комиссии от 3 ноября 2016 г. №87 «Об утверждении Правил надлежащей практики фармаконадзора Евразийского экономического союза» URL:https://docs.eaeunion.org/docs/ru-ru/01411948/cncd_%2021112016_87 (дата обращения 10.03.2017).

6. Naranjo C.A., Busto U., Sellers E.M., Sandor P., Ruiz I., Roberts E.A., Janecek E., Domecq C., Greenblatt D.J. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981; 30 (2): 239-45.

7. WHO Collaborating Centre for Drug Statistics Methodology,Guidelines for ATC classification and DDD assignment 2016. Oslo, 2016 URL:https://www.whocc. no/filearchive/publications/2017_guidelines_web.pdf (дата обращения 09.03.2017)].

8. Воронцов И.М., Мазурин А.В. Пропедевтика детских болезней. - СПб: Фолиант, 2009. - 1008 с

9. Кутехова Г.В., Лепахин В.К., Романов Б.К. Выявление назначения лекарственных средств с нарушениями предписаний инструкции (off-label) в педиатрической практике. Ведомости НЦЭСМП. 2012; 3: 23-27.

10. Титова А.Р., Асецкая И.Л., Поливанов В.А., Зырянов С.К., Глаголев С.В. Структура «off-label» назначений лекарственных препаратов у детей: анализ российской базы данных спонтанных сообщений. Педиатрия. 2016; 95 (6): 75-84.

11. Грацианская А.Н., Бологов А.А., Костылева М.Н., Постников С.С. Применение лекарственных средств off label в педиатрической практике. Заместитель главного врача. 2012; 8.

12. Завидова С.С., Намазова-Баранова Л.С., Тополянская С.В. Клинические исследования лекарственных препаратов в педиатрии: проблемы и достижения. Педиатрическая фармакология. 2010; 7: 1: 6-14.

13. Corny J., Lebel D., Bailey B., Bussi?res J.F. Unlicensed and Off-Label Drug Use in Children Before and After Pediatric Governmental Initiatives. J Pediatr Pharmacol Ther. 2015 Jul-Aug; 20 (4): 316-28.

14. Lindell-Osuagwu L., Hakkarainen M., Sepponen K., Vainio K., Naaranlahti T., Kokki H. Prescribing for off-label use and unauthorized medicines in three paediatric wards in Finland, the status before and after the European Union Paediatric Regulation. J Clin Pharm Ther. 2014 Apr; 39 (2): 144-53.

15. Ekins-Daukes S., Helms P.J., Simpson C.R., TaylorM.W., McLay J.S. Off-label prescribing to children in primary care: retrospective observational study. Eur J Clin Pharmacol. 2004 Jul; 60 (5): 349-5.

16. Костылева М.Н. Оценка безопасности лекарственных средств, применяемых в многопрофильном педиатрическом стационаре. Автореферат диссертации на соискание ученой степени кандидата медицинских наук. М.: 2013.

17. Joret-Descout P., Prot-Labarthe S., Brion F., Bataille J., Hartmann J.F, Bourdon O. Off-label and unlicensed utilisation of medicines in a French paediatric hospital. Int J Clin Pharm. 2015 Dec; 37 (6): 1222-7.

18. Czarniak P., Bint L., Favi? L., Parsons R., Hughes J., Sunderland B. Clinical setting influences off-label and unlicensed prescribing in a paediatric teaching hospital. PLoS One. 2015 Mar 10; 10 (3): e0120630. doi: 10.1371/journal.pone.0120630.

19. Jobanputra N., Save S.U., Bavdekar S.B. Off-label and unlicensed drug use in children admitted to Pediatric Intensive Care Units (PICU). Int J Risk Saf Med. 2015; 27 (3): 113-21.

20. Golocorbin Kon S., Ilikovic I., Mikov M. Reasons for and frequency of off-label drug use. Med Pregl. 2015 Jan-Feb; 68 (1-2): 35-40.

21. Palmaro A., Bissuel R., Renaud N., Durrieu G., Escourrou B., Oustric S., Montastruc J.L., Lapeyre-Mestre M. Off-label prescribing in pediatric outpatients. Pediatrics. 2015 Jan; 135 (1): 49-58.

22. Berdkan S., Rabbaa L., Hajj A., Eid B., Jabbour H., Osta N.E., Karam L., Khabbaz L.R. Comparative Assessment of Off-label and Unlicensed Drug Prescriptions in Children: FDA Versus ANSM Guidelines. Clin Ther. 2016 Aug; 38 (8): 1833-44.

23. Ellul I.C., Grech V., Attard-Montalto S. Paediatric off-label and unlicensed prescribing in primary care in Malta: Prospective observational drug utilisation study. Int J Risk Saf Med. 2015; 27 (3): 123-34.

24. Czaja A.S., Reiter P.D., Schultz M.L., Valuck R.J. Patterns of Off-Label Prescribing in the Pediatric Intensive Care Unit and Prioritizing Future Research. J Pediatr Pharmacol Ther. 2015 May-Jun; 20 (3): 186-96.