Unlicensed and off-label drug use in children - Implications for safety

A significant number of children receive either an unlicensed or an off-label drug during their stay in hospital. Studies throughout Europe have shown that at least one-third of children in hospital and up to 90% of neonates in a neonatal intensive care unit receive such drug prescriptions. The medicines that are most frequently used off-label include analgesics, antibiotics and bronchodilators. The purpose of licensing a drug is to ensure safety, efficacy and quality. If a drug is used in a different manner, one would expect a greater risk of toxicity. Only three studies have commented on the risk of toxicity in relation to unlicensed or off label drug use. Only one of these three studies prospectively tried to evaluate the risk associated with off-label and unlicensed drug prescription. This study suggested that the percentage of unlicensed and off-label drug use was significantly associated with the risk of an adverse drug reaction. Two studies looking at adverse drug reactions suggest that there is a greater risk of a severe adverse drug reaction occurring in association with the off-label or unlicensed use of drugs. One study found that five out of eight severe adverse drug reactions were associated with the off-label use of a medicine. The other study found that 14 of 19 drug prescriptions associated with 17 severe adverse drug reactions were either unlicensed or off-label. The risk of prescribing off-label and unlicensed drugs in children is not clear from the limited data available.