Evolution of paediatric off-label use after new significant medicines become available for adults: a study on triptans in Finnish children 1994-2007

Abstract

What is already known about this subject: • Off-label use in children is widespread. New medicines lack marketing authorization for paediatric use, even when they represent significant therapeutic advantages and are intended for treatment of conditions common in children. • Until now no information exists on how off-label use in children develops over time after a significant new medicine is approved for adults and what happens when it is later labelled for one paediatric age group.

What this study adds: • Off-label use of a new significant medicine begins in adolescents and extends to younger children with delay. First marketing authorization to adolescents, providing a more child-friendly formulation, results in increase of off-label use in younger children, and has limited effect on total off-label use.

Aim: To investigate the evolution of paediatric off-label use after a therapeutically new group of medicines for a common condition becomes available for adults but is labelled for children with a delay of several years.

Methods: Triptans were used as a model, because migraine is common in children, and is the only indication for triptans. Data on all triptan prescriptions 1994-2007 were extracted from the nationwide Finnish Prescription Register. Prescriptions for children were compared over time.

Results: Paediatric patients with triptan prescriptions increased from 204 in 1994 to 2618 in 2007. Sumatriptan accounted for 64% of all paediatric triptan prescriptions. When sumatriptan in a nasal formulation was labelled for children ≥ 12 years in 2003, off-label prescribing to younger children (6-11 years) doubled in 2003-2004. Sumatriptan on-label prescriptions increased to 728 adolescents (45% of sumatriptan in the age group) in 2007, but its off-label use continued also to increase to 1119 (61% of paediatric sumatriptan prescriptions) in 2007. In that year 72% of paediatric triptan use was off-label, 28% on-label.

Conclusions: When a new significant medicine becomes available in adults, off-label use in children starts slowly but continues to extend to younger children reaching a market size which is little influenced by late appearance of a labelled product. Paediatric treatment remains dominated by off-label use despite labelling of a product in an age appropriate formulation to the most relevant age group.

Figure 1

Triptan use in children aged 6–17 years in 1994–2007. Figures include off-label use of sumatriptan and of the other triptans (zolmitriptan, rizatriptan, naratriptan, almotriptan, eletriptan and frovatriptan) and on-label use of sumatriptan in 2003–07. *Approval of nasal sumatriptan for adolescents 12–17 years old in August 2003. On-label use of sumatriptan (); Off-label use of other triptans (); Off-label use of sumatriptan ()

Figure 2

Sumatriptan off-label use in children aged 6–11 years and adolescents aged 12–17 years in 1994–2007 and on-label use of sumatriptan nasal spray 10 mg/dose in adolescents aged 12–17 years in 2003–2007. *Approval of nasal sumatriptan for adolescents 12–17 years old in August 2003. Off-label use age 6–11 years (); Off-label use age 12–17 years (); On-label use 12–17 years ()