TY - JOUR

T1 - Massive presence of off-label medicines in Danish neonatal departments

T2 - A nationwide survey using national hospital purchase data

AU - Gade, Christina

AU - Trolle, Stine

AU - Mørk, Mette Louise

AU - Lewis, Anna

AU - Andersen, Peter Fruergaard

AU - Jacobsen, Thorkild

AU - Andersen, Jon

AU - Lausten-Thomsen, Ulrik

N1 - Publisher Copyright: © 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.

PY - 2023

Y1 - 2023

N2 - There is currently insufficient knowledge of gestational age dependent medicine disposition in neonates. Accordingly, the use of off-label medication, i.e., use of medicines outside its approved marketing authorization, is high in the neonatal departments. By using data from the Danish National Pharmaceutical Hospital Purchase Database, we identified the most commonly occurring medications and calculated the on/off-label ratios for premature and term neonates. Data was extracted on ATC level 5 and based on defined daily doses as per WHO. Data covered the 4 high-level NICUs and 10 of 13 of the intermediate/standard level Danish neonatal departments. Of the identified medication, 87% and 70% did not have approved marketing authorization for use in premature and full-term neonates, respectively. Furthermore, one-fifth of the top 100 medicines did not have a (Danish) marketing license. Overall, off-label medication was widespread covering virtually all ATC groups and no ATC group had an off-label level lower than 50% (range 50%–100%). Finally, in 21% of medications, additives from 8 different chemical groups with potential deleterious effects for neonates were identified. In conclusion, off-label medication in the Danish neonatal departments is widespread. The pharmaceutical industry is unlikely to solve this problem, and we may for a very long time be occasionally forced to use off-label medication. Practical solution must therefore come from multidisciplinary clinical and academic collaboration. Use of formulation list as guidance for prescriptions and NICU-friendly galenic formulations may mitigate the problem temporarily while waiting for definitive studies.

AB - There is currently insufficient knowledge of gestational age dependent medicine disposition in neonates. Accordingly, the use of off-label medication, i.e., use of medicines outside its approved marketing authorization, is high in the neonatal departments. By using data from the Danish National Pharmaceutical Hospital Purchase Database, we identified the most commonly occurring medications and calculated the on/off-label ratios for premature and term neonates. Data was extracted on ATC level 5 and based on defined daily doses as per WHO. Data covered the 4 high-level NICUs and 10 of 13 of the intermediate/standard level Danish neonatal departments. Of the identified medication, 87% and 70% did not have approved marketing authorization for use in premature and full-term neonates, respectively. Furthermore, one-fifth of the top 100 medicines did not have a (Danish) marketing license. Overall, off-label medication was widespread covering virtually all ATC groups and no ATC group had an off-label level lower than 50% (range 50%–100%). Finally, in 21% of medications, additives from 8 different chemical groups with potential deleterious effects for neonates were identified. In conclusion, off-label medication in the Danish neonatal departments is widespread. The pharmaceutical industry is unlikely to solve this problem, and we may for a very long time be occasionally forced to use off-label medication. Practical solution must therefore come from multidisciplinary clinical and academic collaboration. Use of formulation list as guidance for prescriptions and NICU-friendly galenic formulations may mitigate the problem temporarily while waiting for definitive studies.

KW - European Paediatric Regulation

KW - infant

KW - newborn

KW - NICU

KW - off-label medicines

KW - pharmacology

U2 - 10.1002/prp2.1037

DO - 10.1002/prp2.1037

M3 - Journal article

C2 - 36545691

AN - SCOPUS:85144596593

VL - 11

JO - Pharmacology Research & Perspectives

JF - Pharmacology Research & Perspectives

SN - 2052-1707

IS - 1

M1 - e01037

ER -