Adverse Drug Reactions to Off-label Drugs on a Paediatric Ward: an Italian Prospective Pilot Study

Recently published studies examining the extent of off-label drug prescribing in various European paediatric wards have reported that off-label use is widespread and particularly high in Italy. So far, however, no studies have investigated the extent to which adverse drug reactions (ADRs) due to off-label drug use occur in Italy. To evaluate the risk associated with off-label drug use in paediatric inpatients, a prospective surveillance study was carried out in the paediatric ward of a teaching hospital over a 9 month period. Forty-one children (mean age: 7.2 years, 58% male ), out of a study population of 1619 patients, experienced ADRs. In 29 children the ADRs were due to in hospital drug therapies, while in 12 they were due to medicines administered in the community. Urticaria (11 cases), vomiting and rash (5 cases each ) and tremor (4 cases) were the most common ADRs. Eight ADRs (20%) were classified as severe. The drugs most frequently associated with ADRs were salbutamol (5 cases) and coamoxiclav (4 cases). Off-label drug prescriptions were responsible for 38% of inpatient ADRs and for 42% of the ADRs occurring in the community that led to hospitalisation. The use of drugs not licensed for paediatric use (8 cases) or for indications for which the drug was not licensed (6 cases) were the off-label categories most frequently associated with ADRs. Drugs used for diagnostic tests in endocrinology were responsible for one third of ADRs due to off-label uses. The results of this study suggest a high risk of ADRs associated with offlabel prescribing in children, both in the hospital and in the community. This pilot study also demonstrates the feasibility of an ADR monitoring system that could take into account important issues relating to rational drug prescribing in paediatric patients. In order to achieve a comprehensive risk assessment of off-label drug interventions in children, the study should be continued and expanded to involve the community setting as well.