Table of Contents  
RESEARCH ARTICLE
Year : 2013  |  Volume : 4  |  Issue : 5  |  Page : 51-54  

A questionnaire-based study in Calabria on the knowledge of off-label drugs in pediatrics


1 Centro Regionale di Informazione sul farmaco, AO Mater Domini, Catanzaro and Department of Health Science, School of Medicine, University of Catanzaro, Italy
2 Unitą Operativa di Pediatria, Presidio Ospedaliero "Giovanni Paolo II" Lamezia Terme, Azienda Sanitaria di Catanzaro, Italy

Date of Web Publication2-Nov-2013

Correspondence Address:
Luca Gallelli
Chair of Pharmacology, Department of Health Science, School of Medicine University of Catanzaro, Viale Europa, 88100 Catanzaro
Italy
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-500X.120960

Rights and Permissions
   Abstract 

Off-label use is very common among pediatricians, and the main cause is attributable to the lack of drugs specifically designed and marketed for children in different age groups. In this study, we evaluated, through a questionnaire, the knowledge of off-label drugs in pediatrics. Furthermore, we made a directory of 28 off-label drugs most commonly used by pediatricians in agreement with data obtained from Italian Agency for drugs (AIFA) referred to the law no. 648/1996; 180 pediatricians referred to the Italian Society of Pediatrics Calabrian section were asked to complete an online anonymous questionnaire. Eighty five (47.3%) of these completed the anonymous questionnaire, 40% revealed that they used off-label drugs "sometimes"; generally, drugs were used off-label for age and to treat respiratory diseases. For 75 pediatricians (88%) the information about the risk/benefit of off-label drugs is inadequate and 63 pediatricians (74%) did not have a good knowledge about this practice. In conclusion, the knowledge of off-label drugs is very low in pediatricians; more information about off-label drugs could be useful in order to improve the appropriateness of drugs' prescription and to reduce the development of side effects and improving drug safety.

Keywords: Children, off-label drugs, pediatrics, questionnaire


How to cite this article:
Saullo F, Saullo E, Caloiero M, Menniti M, Carbone C, Chimirri S, Paletta L, Gallelli L. A questionnaire-based study in Calabria on the knowledge of off-label drugs in pediatrics. J Pharmacol Pharmacother 2013;4, Suppl S1:51-4

How to cite this URL:
Saullo F, Saullo E, Caloiero M, Menniti M, Carbone C, Chimirri S, Paletta L, Gallelli L. A questionnaire-based study in Calabria on the knowledge of off-label drugs in pediatrics. J Pharmacol Pharmacother [serial online] 2013 [cited 2019 Sep 21];4, Suppl S1:51-4. Available from: http://www.jpharmacol.com/text.asp?2013/4/5/51/120960


   Introduction Top


Off-label use is very common among pediatricians, and the main cause is attributable to the lack of drugs specifically designed and marketed for children in different age groups. In pediatrics, drugs are often prescribed using dosage and indications approved for adults, resulting in increased risk of serious adverse events (including drug therapeutic failure).­ [1],[2],[3],[4] Moreover, physicians when administering drugs to children are frequently forced to deviate from the established labelling indications, by manipulating drug formulation to obtain a pediatric dose or by changing the indicated route of administration. [5] Off-label prescribing could be related to several problems such as safety for the patient, costs for the society, and legal risk for the physician; therefore, this practise should be used only when the benefit outweighs the risk. [6] Italian legislation on the use of off-label drugs is based on law no. 648/1996. Off-label is allowed for drugs included in a specific list, which includes the innovative drugs not yet marketed in Italy, drug still undergoing clinical trials, and medicines administered for a different therapeutic indication not included in the leaflet, in case of absence of therapeutic alternatives and previous written consent of the patient. Italian Law no. 94/1998 allows the physician, in individual cases, to off-label use a drug on the basis of efficacy evidence, under his/her direct responsibility, and after obtaining written informed consent by the patient. This law does not allow the widespread off-label use but permits the physicians to prescribe the appropriate therapy based on data published on the international valuable literature and previously documented demonstration of the absence of other therapeutic alternatives. [6] In this context, the aim of the present study was to evaluate the knowledge of off-label drugs in pediatricians of Calabria region of Italy.


   Materials and Methods Top


In agreement with our previous article, we performed a questionnaire study. [7] This study was prompted on Calabrian pediatricians members of the Italian Society of Pediatrics (SIP) in two phases. The first phase started in December 2012 and finished in March 2013 and was aimed to perform a directory of off-label drugs most commonly used by pediatricians in agreement with data obtained from Italian Agency for drugs (AIFA) referred to the law no. 648/1996. During the second phase, started in April and finished in May 2013, SIP's pediatricians completed an online anonymous questionnaire with 10 answers [Table 1]. The first 5 questions referred specifically to drugs and their off-label use, while the last 5 asked to general guidelines on both risks and limitations of off-label drugs in clinical practice. The answers were analyzed by a working group composed of pharmacists and pharmacologists of the Center of Documentation and Information on Drugs and the Chair of Pharmacology of the University "Magna Graecia" of Catanzaro.
Table 1: Questionnaire completed online by pediatricians


Click here to view



   Results Top


During the first phase, a table of 28 drugs most commonly used as off-label was completed (see [Table 2]). During the second phase, 180 Calabrian pediatricians SIP's members were asked to take part at this study and 85 (47.3%) of them completed the anonymous questionnaire. In particular, 35 were Medical Doctor (MD) General Pediatricians (41%), 32 MD Hospital Pediatricians (38%), 10 MD attending the specialty in Pediatrics (12%), and 8 MD Outpatient Pediatricians (9%). MDs prescribed 341 off-label drugs enclosed in 154 categories of diseases.
Table 2: Most commonly used off-label drugs, in agreement with data of AIFA and list of law no. 648/1996.


Click here to view


40% of MDs revealed that they used off-label drugs "sometimes" [Figure 1], and commonly drugs were used off-label for age [Figure 2] and to treat respiratory diseases [Table 3]; beclomethasone was the most widely used drug [Table 4]. Sixty-six MDs used off-label drugs for lack of formulations approved for pediatric use, while 32 revealed that use of off-label drugs have negative effects on prescriptive appropriateness, although their use may be related with the development of adverse reactions [Table 5]. For 75 pediatricians (88%) the information about the risk/benefit of off-label drugs is inadequate and 63 pediatricians (74%) declared not to have a good knowledge about this practice.
Figure 1: Times of use off-label drugs

Click here to view
Figure 2: Off-label use in agreement with the leaflet of each drug

Click here to view
Table 3: Categories of off-label drugs most frequently prescribed


Click here to view
Table 4: Off-label drugs most frequently prescribed


Click here to view
Table 5: Risks associated with the use of off-label drugs


Click here to view



   Discussion Top


Less than 15% of all the drugs currently marketed and less than half of those specifically intended for children are used on the basis of clinical trials which demonstrate specific features of risk-benefit balance in children. [8],[9],[10] This study was designed to describe the extent of off-label drug use, to identify drugs most commonly used off-label, and to identify factors associated with off-label drugs use in children and above all what is the opinion of pediatricians relative to this problem and their knowledge about it. The data analysis reveals, in agreement with the data in the literature, that in Pediatrics, off-label prescriptions are very numerous, [11],[12],[13] often driven by the lack of specific formulations on the market for children. The off-label drugs most prescribed are those used for diseases of the respiratory tract and the medication most often used in our studied group is Beclomethasone. Pediatricians demonstrate an awareness of the issues related to the use of off-label drugs, and most importantly, they agree with the data in the literature, indicating an increase in the occurrence of adverse reactions. [8],[9],[14],[15],[16],[17] The lack of pediatric formulations on the market is considered a major limitation for clinical practice, but not for prescriptive appropriateness. Most compilers did not consider themselves to be sufficiently well prepared in the off-label use of drugs, and specifically, they consider the information relating to the risks/benefits resulting from such use completely inadequate. In light of all the issues regarding the use of off-label drugs in Pediatrics, the Centre for Documentation and Information on Medicine along with the Chair of Pharmacology at the University "Magna Graecia" in Catanzaro and in collaboration with the regional section of the Italian Society of Pediatrics will begin a drug surveillance project entitled, " Monitoring, Support and Security regarding Off-Label Prescriptions in Pediatrics within the Calabrian Territory". The aim will be to highlight how off-label prescriptions are used within our region, what the issues are relating them and what the possible solutions that could be used.


   Conclusions Top


Pediatric therapies are often complicated by the shortage of medicines on the market that are designed for children of different ages thus forcing the pediatrician towards a problematic off-label use of adult formulations with the increased possibility of adverse reactions and possible medication errors due to the difficulties in administering the right dosage. It would be desirable to increase the studies and clinical trials to support a greater marketing of specific drugs for the pediatric age. In the meantime, it is important to improve the training of pediatricians on the subject, starting with a course of study, in order to make them more prepared to deal with the problem, but also to increase the information on the risks inherent in the use of off-label drugs, so as to increase the awareness of the prescriber. Our task was brought about in order to make aware a very well known but often forgotten problem. We believe that the contribution of pediatricians is a great help in highlighting some aspects of the problem and especially in seeking a possible resolution.

 
   References Top

1.Horen B, Montastruc JL, Lapeyre-Mestre M. Adverse drug reactions and off-label drug use in padiatric outpatients. Br J Clin Pharmacol 2002;54:665-70.  Back to cited text no. 1
    
2.Inpicciatore P, Choonara I, Clarkson A, Provasi D, Pandolfini C, Bonati M. Incidence of adverse drug reactions in padiatric in/out-patients: A systematic review and meta-analysis of prospective studies. Br J Clin Pharmacol 2001;52:77-83.  Back to cited text no. 2
    
3.Turner S, Nunn AJ, Fielding K, Choonara I. Adverse drug reactions to unlicensed and off-label drugs on pèaediatric wards: A prospective study. Acta Paediatr 1999;88:965-8.  Back to cited text no. 3
    
4.Wong I, Sweis D, Cope J, Florence A. Padiatric medicines research in the UK-how to move forward? Drug Saf 2003;26:529-37.  Back to cited text no. 4
    
5.Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr 2005;164:552-8.  Back to cited text no. 5
    
6.Zanon D, Gallelli L, Rovere F, Paparazzo R, Maximova N, Lazzerini M, et al. Off-label prescribing patterns of antiemetics in children: A multicenter study in Italy. Eur J Pediatr 2013;172:361-7.   Back to cited text no. 6
    
7.Gallelli L, Iannacchero R, De Caro E, Peltrone F, Colosimo M, De Sarro G. A questionnaire-based study on prevalence and treatment of headache in young children. J Headache Pain 2005;6:277-80.  Back to cited text no. 7
    
8.The European Parliament and the Council: Regulation on medicinal products for padiatric use and Amending Regulation. Available from: http://eur-lex.europa.eu/LexUriServ/site/en/consleg/2006/R/02006R1901-20070126-en.pdf. [Last accessed on 2013 Jun 13].  Back to cited text no. 8
    
9.ERA-NET PRIOMEDCHILD: European Commission Sixth Framework Programme FP6 Projet no. 036266. Coordination of research on priority medicines for children. Available from: http://www.priomedchild.eu/[Last accessed on 2013 Jun 13].  Back to cited text no. 9
    
10.Anderson M, Choonara I. A systemic review of safety and monitoring and drugs toxicity in published controlled trials antiepilectic drugs in children over a 10 year period. Arch Dis Child 2010;95:731-8.  Back to cited text no. 10
    
11.Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane A, et al. European network for drugs investigation in children. Survey of Unlicensed and off-label drugs use in padiatric wards in European countries. BMJ 2000;320:79-82.  Back to cited text no. 11
    
12.Shah SS, Matthew H, Goodman DM, Feuer P, Sharma V, Fargason C, et al. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med 2007;161:282-90.   Back to cited text no. 12
    
13.Bertuola F, Morando C, Menniti-Ippolito F, Da Cas R, Capuano A, Perilongo G, et al. Association between drug and vaccine use and acute immune thrombocytopenia in childhood: A case-control study in Italy. Drug Saf 2010;33:65-72.  Back to cited text no. 13
    
14.Napoleone E. Children and ADRs (Adverse Drug Reactions). Ital J Pediatr 2010;36:4.  Back to cited text no. 14
    
15.Ferrajolo C, Capuano A, Verhamme KM, Schuemie M, Rossi F, Stricker BH, et al. Drug-induced hepatic injury in children: A case/non-case study of suspected adverse drug reactions in VigiBase. Br J Clin Pharmacol 2010;70:721-8.  Back to cited text no. 15
    
16.Bianciotto M, Chiappini E, Raffaldi I, Gabiano C, Tovo PA, Sollai S, et al. Drug use and upper gastrointestinal complications in children: A case-control study. Arch Dis Child 2013;98:218-21.  Back to cited text no. 16
    
17.Ferrajolo C, Verhamme KM, Trifirò G, ′t Jong GW, Giaquinto C, Picelli G, et al. Idiopathic acute liver injury in padiatric Outpatients: Incidence and Signal Detection in Two European Countries. Drug Saf 2013 [In Press].  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


This article has been cited by
1 Awareness, knowledge and views of off-label prescribing in children: a systematic review
S. Balan,M. A. Hassali,V. S. L. Mak
British Journal of Clinical Pharmacology. 2015; 80(6): 1269
[Pubmed] | [DOI]



 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusions
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed1800    
    Printed67    
    Emailed1    
    PDF Downloaded475    
    Comments [Add]    
    Cited by others 1    

Recommend this journal