Transl Clin Pharmacol.  2014 Dec;22(2):58-63. 10.12793/tcp.2014.22.2.58.

Off-label use and designation of age groupspecific contraindications for pharmacotherapy in children in Korea

• Park MS

• KMID: 2050937
• DOI: http://doi.org/10.12793/tcp.2014.22.2.58

Abstract

Children should be treated with medicines that have been tested for efficacy and safety in the given age groups. In reality the majority of drugs being used in children lack such information, inevitably leading to the "off-label use." Over decades there have been concerns regarding risk of adverse effects with such off-label uses. However, in most countries rational application of off-label uses have not been prohibited, since it may be the only available and perhaps the best possible treatment option. In contrast, in an effort to minimize such use and per se 'protect' children from possible harm associated with it, Korea has launched "Drug Utilization Review" system, which included age group-specific contraindications, based on the labeling information approved by Ministry of Food and Drug Safety. The problem lies in the definition and scope of 'contraindication.' Lack of evidence for safety and concern for risk of serious adverse drug reactions are the basis for contraindication. This leads to branding of off-label uses as contraindications in certain age groups. This policy is restricting the already scarce treatment options and suffocating the initiative for developing better pharmacotherapy for children. We should learn from other countries that have travailed more to provide better medicines to children. Clinical trials of new drugs as well as existing drugs in pediatric populations are strongly encouraged. Simple prohibition of off-label use is not the answer, but rather systematized management of off-label use as well as conduct of clinical trials in pediatric age groups must be encouraged and supported.

Keyword

Children; Drug Safety; Off-label; Contraindication; Clinical Trials

MeSH Terms

Child*
Drug Therapy*
Drug-Related Side Effects and Adverse Reactions
Humans
Korea
Off-Label Use*

Reference

References

1. ICH Harmonised Tripartite Guideline_Clinical Investigation of Medicinal Products in the Pediatric Population. E11.

2. Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr. 2005; 164:552–558.

3. Conroy S, McIntyre J, Choonara I. Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed. 1999; 80:F142–F145.

4. Shah SS, Hall M, Goodman DM, Feuer P, Sharma V, Fargason C Jr, et al. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med. 2007; 161:282–290.

5. Mason J, Pirmohamed M, Nunn T. Off-label and unlicensed medicine use and adverse drug reactions in children: a narrative review of the literature. Eur J Clin Pharmacol. 2012; 68:21–28. doi: 10.1007/s00228-011-1097-1.

6. Bellis JR, Kirkham JJ, Thiesen S, Conroy EJ, Bracken LE, Mannix HL, et al. Adverse drug reactions and off-label and unlicensed medicines in children: a nested case-control study of inpatients in a pediatric hospital. BMC Medicine. 2013; 11:238. doi: 10.1186/1741-7015-11-238.

7. Choonara I, Conroy S. Unlicensed and Off-Label Drug Use in Children: Implications for Safety. Drug Saf. 2002; 25:1–5.

8. Magalhães J, Rodrigues AT, Roque F, Figueiras A, Falcão A, Herdeiro MT. Use of off-label and unlicenced drugs in hospitalised paediatric patients: a systematic review. Eur J Clin Pharmacol 2014. [Epub ahead of print].

9. Lindell-Osuagwu L, Korhonen MJ, Saano S, Helin-Tanninen M, Naaran-lahti 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; 34:277–287.

10. Guidelines on Designation of Drugs Contraindicated for Concomitant Use and Others. Korea Ministry of Food and Drug Safety Guideline 2014–2 (enacted on 2014. 1. 9).

11. Cambridge Advanced Learner's Dictionary.

12. USFDA label on ATIVAN (lorazepam) Injection. http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018140s028lbl.pdf. Accessed 20 Mar. 2010.

13. American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997; 99:268–278.

14. Studies into provision of clinical research and evaluation methods of unapproved uses of drugs. MFDS Project Report. 2012. 11172_Rules on Safety of Medicine_301.

15. Regulatory Information. "Off-Label" and Investigational Use Of Marketed Drugs, Biologics, and Medical Devices – Information Sheet. http://www.fda.gov/RegulatoryInformation/Guidances/ucm126486.htm. Accessed 20 Oct. 2014.

16. Guidance for Industry. Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm285145.pdf. Accessed 10 Oct. 2011.

17. The Tatia Oden French Memorial Foundation Petition. http://www.fda.gov/ohrms/dockets/dailys/04/nov04/112304/04p–0522-cp00001–01-vol1.pdf. http://www.fda.gov/ohrms/dockets/dailys/04/nov04/112904/04p-0522-cp00002-01-vol1.pdf;ahttp. ://. www.fda.gov/ohrms/dockets/dockets/04p0522/04p-0522-sup0001-01-vol1.pdf. Accessed 10 Oct. 2011.

18. FDA CDER to The Tatia Oden French Memorial Foundation Petition Partial Approval and Denial.pdf. http://www.regulations.gov/contentStreamer. ?objectId=0900006481170168&disposition=attachment&contentType=p df. Accessed 10 Oct. 2011.

19. FDA Drug Safety Communication: New warnings against use of terbutaline to treat preterm labor. http://www.fda.gov/Drugs/DrugSafety/ucm243539. htm. Accessed 10 Oct. 2011.

20. FDA News & Events. Speeches by FDA Officials. Scott Gottlieb, MD – Washington, DC.http://www.fda.gov/newsevents/speeches/ucm051792. htm. Accessed 10 Oct. 2011.

21. The Food and Drug Administration Safety and Innovation Act (FDASIA): Summary of GDUFA, MDUFA, BsUFA and Pediatrics. http://www.poli-cymed.com/2012/07/the-food-and-drug-administration-safety-and-inno-vation-act-fdasia-summary-of-gdufa-mdufa-bsufa.html. Accessed 7 Aug. 2012.

22. Roberts R, Rodriguez W, Murphy D, Crescenzi T. Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. JAMA. 2003; 290:905–911.