Adverse drug reactions and off-label and unlicensed medicines in children: a nested case?control study of inpatients in a pediatric hospital

Jennifer R Bellis,Munir Pirmohamed,Jennifer C Duncan,Louise E Bracken,Anthony J Nunn,Jamie J Kirkham,Elizabeth J Conroy,Kim A Bird,Matthew Peak,Rosalind L Smyth,Signe Thiesen,Mark A Turner,Helena L Mannix

doi:10.1186/1741-7015-11-238

Abstract

BackgroundOff-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice. Using data from a prospective cohort study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to test the hypothesis that OLUL status is a risk factor for ADRs.MethodsA nested case?control study was conducted within a prospective cohort study. Details of all medicines administered were recorded, including information about OLUL status. The odds ratio for OLUL medicines being implicated in a probable or definite ADR was calculated. A multivariate Cox proportional hazards regression model was fitted to the data to assess the influence that OLUL medicine use had on the hazard of an ADR occurring.ResultsA total of 10,699 medicine courses were administered to 1,388 patients. The odds ratio (OR) of an OLUL medicine being implicated in an ADR compared with an authorized medicine was 2.25 (95% confidence interval (CI) 1.95 to 2.59). Medicines licensed in children but given to a child below the minimum age or weight had the greatest odds of being implicated in an ADR (19% of courses in this category were implicated, OR 3.54 (95% CI 2.82 to 4.44). Each additional OLUL medicine given significantly increased the hazard of an ADR (hazard ratio (HR) 1.3 95% CI 1.2 to 1.3, P <0.001). Each additional authorized medicine given also significantly increased the hazard (HR 1.2 95% CI 1.2 to 1.3, P <0.001).ConclusionsOLUL medicines are more likely to be implicated in an ADR than authorized medicines. The number of medicines administered is a risk factor for ADRs highlighting the need to use the lowest number of medicines, at the lowest dose for the shortest period, with continual vigilance by prescribers, in order to reduce the risk of ADRs.

Highlights

Off-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice
Category 5: medicines licensed in children but given to a child below the minimum age or weight had the greatest risk of being implicated in an adverse drug reactions (ADRs)
Despite this, OLUL medicines were still more likely to be implicated in an ADR than authorized medicines

Summary

Introduction

Off-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice. The MA sets out terms of use for the medicine This does not preclude the use of regulation in the EU [3] and the Pediatric Research Equity Act of 2003 in the US [4] are likely to improve the situation, it is going to take time. The use of OLUL medicines in children is a potential risk factor for adverse drug reactions (ADRs). In a study of 936 patients, Turner et al found that the proportion of OLUL medicines administered to pediatric inpatients was significantly associated with ADR risk [5]. This has not been demonstrated by all studies, many of which were small, employed different methodologies and used inexact and varying definitions. There is a need for further research in this area [6]

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