Adverse drug reactions to unlicensed and off-label drugs on paediatric wards: a prospective study

Abstract

To determine the incidence of adverse drug reactions (ADRs) to unlicensed and off-label drugs used in paediatric inpatients, we carried out prospective surveillance on five different paediatric wards in a regional children's hospital for 13 wk. Comparison of the use of each drug with its summary of product characteristics was made to determine whether the drug was used in an unlicensed or off-label manner. The presence of an ADR was determined using previously defined criteria. In total, 4455 courses of drugs were administered to 936 patients in 1046 admissions. In 507 (48%) of the 1046 admissions, patients received one or more unlicensed or off-label drugs. ADRs occurred in 116 (11%) of the 1046 patient admissions. ADRs were associated with 112 (3.9%) of the 2881 licensed drug prescriptions and 95 (6%) of the 1574 unlicensed or off-label drug prescriptions. Use of drugs in an off-label or unlicensed manner to treat children is widespread. ADRs are a significant problem following unlicensed or off-label drug prescriptions.

Adverse Drug Reactions in Hospitalised Children in Germany Are Decreasing: Results of a Nine Year Cohort-Based Comparison

“…We found an overall ADR incidence of 13.1% (95% CI, 9.8–16.3) which is slightly above the findings published previously [5], [6], [8], [12]. However, it is still lower than the overall incidence observed in our large international multi-centre study [15].…”

“…It has been shown that the incidence of ADRs in hospitalized children is about 10% [5], [6], [8],[12]. A large systematic review by Smyth et al indicated that the incidence rate for ADRs causing hospital admission is 2.9% [11].…”

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

“…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). [1234] 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.…”

Development of Drug Therapies for Newborns and Children

“…Many studies have shown that off-label drug use in pediatrics is associated with significantly increased risk for developing adverse drug reactions. 27,28 …”