• adverse drug reactions;
  • children;
  • Denmark;
  • off-label;
  • pharmacoepidemiology;
  • pharmacovigilance


• Off-label use of medicine in children is common, as few medications are licensed for use in this population.

• There is concern about off-label use of medicines in children due to lack of knowledge about safety beyond the indication area described in the official product information documented in the licensing material.


• One-fifth of all ADRs reported over a decade in Danish children were associated with off-label prescribing of medicines.

• Serious ADRs from off-label prescribing primarily appeared in therapeutic groups: allergens, dermatologicals and sex hormones.

• Until more clinical studies are conducted in children, prescribers and carers must be aware of the risk of potentially serious ADRs from off-label prescribing, and the safety of off-label prescribing in the paediatric population should be closely monitored.

AIM To identify adverse drug reactions (ADRs) associated with off-label prescribing of medicines in a paediatric population.

METHODS We analysed spontaneous ADR reports for children from ages 0 to 17 years submitted to the Danish national ADR database from 1998 to 2007. We defined off-label prescribing as prescriptions outside the licensed age group. Off-label ADRs were categorized by therapeutic group, age of child, type and severity. The unit of analysis was one ADR.

RESULTS We analysed 4388 ADRs for children reported in the national database. Approximately 17% of reported ADRs were associated with off-label use, 60% of them serious. More than one half of off-label ADRs were reported in adolescents. Serious ADRs due to off-label prescribing are more likely to be reported for hormonal contraceptives (ATC group G), anti-acne preparations (ATC group D) and allergens (ATC group V).

CONCLUSION One-fifth of all ADRs reported over a decade in Danish children was associated with off-label prescribing, and serious ADRs due to off-label prescribing were primarily present in three therapeutic groups: sex hormones, dermatologicals and allergens. There is a need for more research into the prescribing of these medicines in the teenage population, as well as tighter reporting and monitoring of ADRs for medicines prescribed off-label in the paediatric population.