Use of off-label and unlicensed drugs in the neonatal intensive care unit and its association with severity scores

Abstract

Objective: To analyze the frequency of unlicensed (UL) and offlabel (OL) prescriptions in neonates admitted to the neonatal intensive care unit of a tertiary care hospital and to determine their association with patients' severity. Methods:Observational cohort study including drugs prescribed during hospitalization of neonates over a 6-week period between July and August 2011. The drugs were classified as UL and OL for dose, frequency, presentation, age group, or indication, according to an electronic list of drugs approved by the Food and Drug Administration. Patients were followed until hospital discharge or 31 days of hospitalization, with daily records of the Neonatal Therapeutic Intervention Scoring System (NTISS). Results:We identified 318 prescription items for 61 patients (average of five items/patient); there were only 13 patients with appropriate use of medications (21%). A prevalence of 7.5% was identified for UL prescriptions and 27.7% for OL, and the most prevalent OL use was that related to age group -19.5%. Fifty-seven medications were computedone patient received 10 UL/OL drugs during hospitalization. The prevalence of OL uses was higher in preterm infants < 35 weeks and in those with higher severity scores (p = 0.00). Conclusions:The prevalence of neonates exposed to UL/OL drugs during hospitalization was high, especially for those with higher NTISS scores. Although there is general appreciation that neonates, especially preterm infants, have a high rate of drug use, an assessment including different cultures and countries is still needed to prioritize areas for future research in the pharmacotherapy of this vulnerable population.J Pediatr (Rio J). 2012;88(6):465-70: Drugs, drug labeling, injury severity score, neonatology. ResumoObjetivo: Avaliar a frequência da prescrição de medicamentos de uso não licenciado (UL) e off-label (OL) em recém-nascidos internados em unidade de tratamento intensivo neonatal de hospital de nível terciário e verificar a associação do seu uso com a gravidade dos pacientes.Métodos: Estudo observacional de coorte dos medicamentos prescritos no período de 6 semanas da internação de neonatos, entre julho e agosto de 2011. Os medicamentos foram classificados em UL e OL para dose, frequência, apresentação, faixa etária e indicação, de acordo com bulário eletrônico aprovado pela Food and Drug Administration. Os pacientes foram acompanhados até alta hospitalar ou 31 dias de internação, com registro diário do Neonatal Therapeutic Intervention Scoring System. Resultados:Foram identificados 318 itens de prescrição para 61 pacientes (média de cinco itens/paciente) e apenas 13 pacientes com uso de medicamentos adequados (21%). Identificaram-se prevalên-cias de 7,5% para prescrições UL e de 27,7% para OL. O uso OL mais prevalente foi para medicamentos não padronizados para faixa etária -19,5%. Computaram-se 57 medicações -um paciente recebeu 10 fármacos UL/OL na internação. A prevalência de usos OL foi maior em prematuros < 35 semanas e nos com escores de gravidade mais ele...

Off-Label and Unlicensed Drug Use in Neonatology: Reality in a Portuguese University Hospital

“…12,13,19 With regard to the higher number of drugs necessary in preterm neonates (median = 4), it confirms the current knowledge that younger, lighter and most vulnerable newborns receive more drugs than the more matures. [13][14][15] Beyond the classical division into off-label and unlicensed drugs, we chose to add 'undetermined state approval' and 'contraindicated' categories, in order to be more precise in data analysis. However, typically they are included in off-label category by other authors.…”

“…9,12 For this reason, just like sick full-term newborns are more exposed to the off-label/unlicensed medications, the most premature and low birth weight neonates receive the greatest number of drugs. [13][14][15] Moreover, there are also the specific pharmacokinetics and the fast body mass and composition change of newborns, making them particularly susceptible to the risks of developing adverse drug reactions (ADRs) or experiencing errors in adjusting doses or formulations. 5,6,9,10 In 2010, European Medicines Agency (EMA) published a report that describes existing data on paediatric uses of medicinal products by country.…”

Medication safety in neonatal care: a review of medication errors among neonates

“…2. It is reported that the number of medications administered in the NICU is inversely proportional to the patients gestational age or their weight [Carvalho et al 2012]. …”

The conundrum of off-label and unlicensed drug usage in neonatology

“…Nesta edição do Jornal de Pediatria, Carvalho et al 9 Não foram declarados conflitos de interesse associados à publicação deste editorial.…”

“…Nesta edição do Jornal de Pediatria, Carvalho et al 9 relatam os resultados de um estudo prospectivo observacional de coorte realizado no Brasil, que avaliou o uso de medicamentos off-label e não licenciados na UTIN. Seus resultados confirmam o que estudos prévios de outros países também haviam demonstrado: pouquíssimos pacientes (21%) medicados na UTIN atenderam aos requisitos para uso adequado.…”