Off‐label drug use in neonates and infants in Spain: A five‐year observational study

Abstract

Objectives: To provide information about the off-label rate of all drug prescriptions in neonates and infants up to 1 year in Spain. Also, to analyse the off-label prescription of medicines under current practice in this age group according to different evidence sources.Study design: A five-year (2015-2019) exploratory observational study about off-label prescription in neonates and infants (0 to 1 year) at primary health care in Spain. All drug prescriptions in this age group were analysed and classified according to their labelling in off-label or on-label. The drugs prescribed off-label were subsequently reviewed in national formularies and other databases to assess its evidence of use beyond what is recommended in the Summary of Product Characteristics (SmPC).Results: On average 34.50% of total prescriptions were prescribed off-label according to the SmPC. 17.93% of total prescriptions in neonates and infants up to 1 year old were not based on clinical evidence from SmPC, Pediamécum, BNF or DailyMed. In more than 88% of cases, off-label use was related to the posology section of the SmPC, followed by the therapeutic indications and contraindications sections, in 35.20% and 24.10% of cases, respectively. Almost 13% of off-label drugs were over-the-counter. Salbutamol followed by topical tobramycin and colecalciferol were the drugs most prescribed off-label.Conclusions: Off-label use of drugs remains as an important public health concern, especially for neonates and infants up to 1 year, who receive the greatest proportion of offlabel prescriptions. The evidence-based off-label prescription is a widespread practice that has shown a stable trend during the 5-year study period providing also a certain extent of flexibility to paediatricians in some therapeutic decisions.

From Prescription Drugs to Natural Health Products: Medication Use in Canadian Infants

“…There are several caveats to evaluating NHP product use in terms of “off-label” and “unlabeled” since these terms are not universally defined, and NHPs are notoriously difficult to classify due to country-specific variations in their regulatory approval [ 23 ]. Having said this, our rates for off-label use are of the same magnitude as other developed countries [ 2 , 24 , 25 , 26 , 27 ]. Off-label medication treatment of children is well described in the hospital setting, involving up to 65% of prescription drugs in pediatric and neonatal units [ 26 ].…”

“…Off-label medication treatment of children is well described in the hospital setting, involving up to 65% of prescription drugs in pediatric and neonatal units [ 26 ]. Fewer studies—none in Canada—have investigated this issue from an outpatient perspective [ 25 , 26 , 27 , 28 ].…”

Prescribed medicine use and extent of off‐label use according to age in a nationwide sample of Australian children

“…These findings do not apply to other settings, such as in hospitals, where off-label prescribing is likely to be higher. 30,31 Off-label prescribing has also been shown to be high in newborns, especially in intensive care units 32,33 ; however, we were unable to explore this population due to the lack of exact date of birth and the incomplete capture of medicine use in hospitals. More in-depth studies of this population in the Australian context are warranted.…”

Neonatal Drug Formularies—A Global Scope

“…Several studies have been conducted in an attempt to quantify the off-label prescription rate in neonates. These include a 5-year observational study from Spain by Lizano-Díez et al [4], which demonstrated that 34.10% of drugs prescribed to neonates over a period of 2 years were prescribed off-label. A prospective cohort study by Costa et al [5] examined the prevalence of neonates administered off-label and unlicensed drugs in a neonatal intensive care unit (NICU) in Brazil and found that 96.4% of neonates and 100% of extremely preterm neonates or extremely low birth weight neonates were exposed to off-label drugs, while 66.8%, 76.7% and 75.7% were exposed to unlicensed drugs, respectively.…”