Medication Use in the Neonatal Intensive Care Unit and Changes from 2010 to 2018

Stark, Ashley; Smith, P. Brian; Hornik, Christoph P.; Zimmerman, Kanecia O.; Hornik, Chi Dang; Pradeep, Sidart; Clark, Reese H.; Benjamin, Daniel K.; Laughon, Matthew M.; Greenberg, Rachel G.

doi:10.1016/j.jpeds.2021.08.075

Cited by 85 publications

(60 citation statements)

References 32 publications

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“…Medical treatment of PDA was described in 4202 infants during a 4-year period in South Korea (population of 51.2 million) by Park et al in an analysis of national epidemiologic data [14]. Caffeine is one of the top five most prescribed treatments in neonatology, 156 exposures, 199 courses and 3908 days of use per 1000 infants discharged from 305 NICUs managed by the Pediatrix Medical group from 2005-2010 (450,386 infants) [15]. Anderson et al described the incidence of infantile hemangioma, the third indication, with 1.64 per 100 person years in a predominantly white, non-Hispanic US population.…”

Section: Discussionmentioning

confidence: 99%

The Use of Off-Label Medications in Newborn Infants Despite an Approved Alternative Being Available—Results of a National Survey

et al. 2022

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Neonates continue to be treated with off-label or unlicensed drugs while in hospital. However, some medications that have previously been used in adults underwent clinical testing and licensure for use with a different indication in the neonatal and pediatric population. Almost always, the marketing of these newly approved substances in a niche indication is accompanied by a steep increase in the price of the compound. We investigated the use of the approved formulation or the cheaper off-label alternative of Ibuprofen (Pedea®), Propanolol (Hemangiol®) and Caffeine Citrate (Peyona®) in neonatal clinical practice by conducting a National Survey of 214 Perinatal Centers in Germany. We also assessed price differences between on- and off-label alternatives and the extend of the clinical development program of the on-label medication in the neonatal population. On-label medication was more frequently used than the off-label alternative in all indications (PDA: on-label to off-label ratio 1:0.26, Apnea: 1:0.56, Hemangioma 1:0.76). All sponsors did conduct placebo-controlled Phase III trials with efficacy and safety endpoints in the target population and the number of participants in the target population varied between 82 and 497. Costs for the three drugs in their approved and marketed formulations increased in median 405-fold compared with the corresponding off-label alternative. Overall, about one out of three neonatologists prescribed an off-label or non-approved drug to patients despite an alternative medication that is approved for the indication in the target population being available.

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Section: Discussionmentioning

confidence: 99%

The Use of Off-Label Medications in Newborn Infants Despite an Approved Alternative Being Available—Results of a National Survey

et al. 2022

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“…More generally, the leading position of GENT is widely recognized, but the rank of AMK varies according to studies. A recent US study by Stark et al [21, in press] describes a cohort of approximately 800,000 newborns from 363 NICU in the Pediatrix Medical Group; GENT ranks 2nd on the list of all drugs prescribed during 2010–2018, tobramycin ranks 27th, and amikacin ranks 70th [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Prescription of Aminoglycosides in 23 French Neonatal Intensive Care Units

Martin-Mons

Gouyon²,

Lorrain

et al. 2021

Antibiotics

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Background: Aminoglycosides are the most prescribed antibiotics in neonatal intensive care units (NICU). Reducing exposure to antibiotics in the NICU is highly desirable, particularly through benchmarking methods. Methods: Description of aminoglycosides prescriptions in 23 French NICU using the same computerized system over a 4-year period (2017–2020). A benchmarking program of antibiotics prescription was associated. Results: The population included 53,818 patients. Exposition rates to gentamicin and amikacin were 31.7% (n = 17,049) and 9.1% (n = 4894), respectively. Among neonates exposed to gentamicin, 90.4% of gentamicin and 77.6% of amikacin treatments were started within the 1st week of life. Among neonates exposed to amikacin, 77.6% started amikacin within the 1st week. The average daily dose of gentamicin at first prescription increased over the study period from 3.9 in 2017 to 4.4 mg/kg/d in 2020 (p < 0.0001). Conversely, the corresponding amikacin daily doses decreased from 13.0 in 2017 to 12.3 mg/kg/d in 2020 (p = 0.001). The time interval between the first 2 doses of gentamicin was mainly distributed in 3 values during the first week of life: 49.4% at 24 h, 26.4% at 36 h, and 22.9% at 48 h. At first amikacin prescription, the time interval was distributed in 4 categories: 48% at 24 h, 4.1% at 30 h, 8.5% at 36 h, and 37.1% at 48 h. As compared to literature guidelines, the rates of overdose and underdose in gentamicin (1.5% and 2.7%) and amikacin (0.3% and 1.0%). They significantly decreased for gentamicin over the study period. In multivariate analysis, the factors significantly associated with GENT overdose were the year of admission, prematurity, length of stay, and duration of the treatment. Conclusion: This prescription strategy ensured a low rate of overdose and underdose, and some benefits of the benchmarking program is suggested.

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“…Drug use patterns were found to be generally uniform with antibiotics being the most frequently prescribed drug in the neonatal department ( Al-Turkait et al, 2020 ). Naturally, trends in general drug prescription have changed over the years but off-label drug use in premature children is still very common: of the top 50 medications of extremely low birth weight premature infants, only 40% were FDA-labeled for use in infants ( Stark et al, 2021 ). This represents a relative lack of proper pharmacokinetic (PK) studies in premature children and remedying this will likely be a long haul due to the difficulties of conducting clinical PK studies in preterm children.…”

Section: Prematuritymentioning

confidence: 99%

The Blind Spot of Pharmacology: A Scoping Review of Drug Metabolism in Prematurely Born Children

et al. 2022

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The limit for possible survival after extremely preterm birth has steadily improved and consequently, more premature neonates with increasingly lower gestational age at birth now require care. This specialized care often include intensive pharmacological treatment, yet there is currently insufficient knowledge of gestational age dependent differences in drug metabolism. This potentially puts the preterm neonates at risk of receiving sub-optimal drug doses with a subsequent increased risk of adverse or insufficient drug effects, and often pediatricians are forced to prescribe medication as off-label or even off-science. In this review, we present some of the particularities of drug disposition and metabolism in preterm neonates. We highlight the challenges in pharmacometrics studies on hepatic drug metabolism in preterm and particularly extremely (less than 28 weeks of gestation) preterm neonates by conducting a scoping review of published literature. We find that >40% of included studies failed to report a clear distinction between term and preterm children in the presentation of results making direct interpretation for preterm neonates difficult. We present summarized findings of pharmacokinetic studies done on the major CYP sub-systems, but formal meta analyses were not possible due the overall heterogeneous approaches to measuring the phase I and II pathways metabolism in preterm neonates, often with use of opportunistic sampling. We find this to be a testament to the practical and ethical challenges in measuring pharmacokinetic activity in preterm neonates. The future calls for optimized designs in pharmacometrics studies, including PK/PD modeling-methods and other sample reducing techniques. Future studies should also preferably be a collaboration between neonatologists and clinical pharmacologists.

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Medication Use in the Neonatal Intensive Care Unit and Changes from 2010 to 2018

Cited by 85 publications

References 32 publications

The Use of Off-Label Medications in Newborn Infants Despite an Approved Alternative Being Available—Results of a National Survey

The Use of Off-Label Medications in Newborn Infants Despite an Approved Alternative Being Available—Results of a National Survey

Prescription of Aminoglycosides in 23 French Neonatal Intensive Care Units

The Blind Spot of Pharmacology: A Scoping Review of Drug Metabolism in Prematurely Born Children

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