Paediatric drug use with focus on off-label prescriptions in Lombardy and implications for therapeutic approaches

Abstract

The persistent lack of information on the paediatric use of most medicinal products is a major hindrance towards an optimal treatment of paediatric patients. Several studies have documented the high prevalence of off-label use in paediatric population. No comprehensive studies, however, exist that analyse in full all prescriptions for all dispensed drugs, especially in view of the recent intervention by the European Medicine Agency to tackle this issue. We have assessed the drug prescription pattern in the paediatric outpatient population of Lombardy, which has a reliable record of such prescriptions focusing on off-label drug use. We analysed all dispensed outpatient prescriptions to children aged 0-18 years and the proportion of off-label drug use in 2011, using data from the regional administrative prescriptions database. A total of 4,027,119 prescriptions were dispensed, of which 133,619 (3.3 %) were off-label. The anatomical therapeutic chemical classes most involved in off-label prescriptions were antibiotics for systemic use (33,629), alimentary tract and metabolism (31,739) and respiratory tract (31,458). The highest rate (8 %) of off-label drug prescriptions was observed in the age range 0-1. The study revealed also an inappropriate prescription pattern for fluoroquinolones and drugs targeting the cardiovascular and musculoskeletal systems. We identified inappropriate prescriptions for specific drug classes, highlighting the need of increasing pharmacological studies in the paediatric patients and specific critical drugs/drug classes in which such studies are particularly urgent. Depending on the region, inappropriate paediatric drug prescriptions may affect different drug classes, indicating the need of tailoring specific programmes of information.

Off-Label Prescribing in Pediatric Outpatients

“…When we compare diagnosis profiles, respiratory symptoms are still the most common but with a lower prevalence (38.7% vs 56.5% in 2000). Symptoms (eg, fever) were more common in our study (16 [20][21][22] on prescription databases revealed high off-label rates, from 13.5% to 62%, except an Italian study 23 with a 3.3% rate. This heterogeneity in results could be explained by differences in off-label definitions.…”

“…The most common classes in the Italian study 23 were antibiotics and drugs for the alimentary tract, metabolism, and the respiratory tract. However, the age groups were not strictly similar; the Swedish study 22 exposed to tixocortol, exhibited a lower rate of unlabeled indications related to this drug.…”

Can Registration Procedures of Pharmaceuticals Inadvertently Contribute to Off-Label Prescribing in Children?

“…Similar findings have been reported by other investigators. [26][27][28][29][30][31] In view of this fact, the authors reviewed the product literature of those respiratory medicines and antibiotics that had been prescribed in an off-label manner in the study by Ellul et al 18 These medicines were classified according to the Anatomical Therapeutic Chemical (ATC) system by using the Guidelines for ATC classification and Defined Daily Dose assignment. 32 Subsequently, the product literature, containing the same active ingredient(s) but produced by different marketing authorization holders, were compared with each other to screen for inconsistencies between them.…”

“…This regulatory requirement traces its origins to Council Directive 65/65/ EEC of January 26,1965, which laid down the 3 basic criteria on which marketing authorizations are based: quality, safety and efficacy. 2,3 In Malta, the smallest member state of the EU, pharmaceutical regulation is governed by the Licensing Authority, which is the Maltese competent authority, enacted through the Medicines Act (Act III of 2003).…”

“…Although medicines may be identical with respect to the active ingredient and formulation, if marketed by different marketing authorization holders, the information found in the summaries of product characteristics may differ, leading to off-label prescribing by physicians. 18,19 One of the most compelling illustrations of inconsistencies in the product literature that has given rise to off-label use concerns etanercept powder for injection. The summary of product characteristics of etanercept, centrally authorized by EMA, includes as an indication the treatment of juvenile idiopathic arthritis (JIA) in patients ''who have had an inadequate response to, or who have proved intolerant of, methotrexate.…”