Off-Label and Unlicensed Medicines' Related Problems in Paediatric In-Patients

Abstract

Background: Current legislations such as paediatric investigation plan (PIP) require pharmaceutical companies seeking marketing authorisation for a new medicine to provide evidence of studies in paediatrics to justify the use of such medicine in this population. In spite of these legislations, there are still challenges with conduct of clinical trials in paediatrics; thus, there is lack of commercially available dosage forms appropriate for use in this population. Consequently, a good proportion of medicines used in treating paediatric patients are used in the unlicensed (UL) or off-label (OL) manner. Use of UL or OL medicines has been associated with higher safety incidents such as, adverse drug reactions (ADRs) than licensed medicines. ADRs are only a subset of medicine related problems (MRPs) associated with the use of medicines. Currently, no studies have explored all aspects of problems associated with the use of OL and UL medicines in paediatrics. Aim: To investigate the prevalence of the use of OL and UL medicines and problems associated with their use in paediatrics patients admitted to intensive care units of a Children’s Hospital. Method: A systematic literature review was carried out to identify problems that are associated with the use of OL and UL medicines. A retrospective review of case notes (n=194) of patients who were admitted to Paediatric Intensive Care Unit (PICU) was carried out at medical records units of the hospital. This was followed by a prospective review of case notes (n=147) of patients admitted to PICU. The last study involved a prospective review of case notes (n=87) admitted to Neonatal Intensive Care Unit (NICU); NICU had migrated to electronic prescribing at the time the study was carried out. Licensing status of medicines was determined using Summary of Product Characteristics of medicines. Definition and categories of MRPs were based on the Pharmaceutical Care Network Europe classification system version 6.2. Naranjo causality scale was used to identify the medicines that was associated with MRPs. Severity and preventability of identified MRPs were assessed using the National Patient Safety Agency categorisation for level of harm and Schumock and Thornton scale respectively. Data was analysed using computer programmes including Excel, Statistical Package for the Social Sciences and STATA. Results: In the retrospective study, 53% of the total number of patients developed at least one MRP and 8% (n=165/2000) of the total number of medicines were associated with MRPs. From the total number of MRPs, 43% were associated with licensed medicines, while 57% were associated with OL and/or UL medicines. Identified MRPs were mostly ADRs and treatment effectiveness problems (84% vs.16%). In the prospective PICU study, 66% of the total number of patients developed at least one MRP and 11% (n=178/1578) of prescribed medicines were associated with MRPs. From the total number of MRPs, 40.4% were associated with licensed medicines, while 59.6% were associated with OL and/or UL medicines. Among the identified MRPs, 83% were ADRs and 17% were treatment effectiveness problems. In the NICU study, 90% of the patients developed MRPs and 9% (n= 186/1978) of the total number of medicines were associated with MRPs. From the total number of MRPs, 55% were associated with licensed medicines, while 45% were associated with OL and/or UL medicines. All the identified MRPs were ADRs. Conclusion: This research is the first to investigate MRPs associated with the use of OL and UL medicines in paediatric in-patients. MRPs associated with the use of OL and UL medicines were higher than with the use of licensed medicines. Inclusion of paediatrics in clinical trials of new medicines is fundamental to reducing the use of OL and UL medicines and the problems associated with their use.