Abstract
BackgroundA multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted.MethodsA multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE.ResultsPrescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified.ConclusionsNeonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.
Highlights
Excipients have many functions in pharmaceuticals, including solubility and stability modulation, and as preservative agents, colorants, or sweeteners, which are necessary to maintain quality and improve patient acceptability of medicines [1]
Several reports suggest that potentially harmful excipients (PHEs) are included in drugs prescribed for neonates [4, 7,8,9,10,11,12,13]
In Japan, solid dosage forms are mainly administered as oral dosage forms, which reduces the amounts of sweeteners, dissolving agents, and preservative agents required compared to liquid dosage forms; the frequency of neonatal exposure to excipients may be assumed to be different [17,18,19]
Summary
Excipients have many functions in pharmaceuticals, including solubility and stability modulation, and as preservative agents, colorants, or sweeteners, which are necessary to maintain quality and improve patient acceptability of medicines [1]. Several reports suggest that potentially harmful excipients (PHEs) are included in drugs prescribed for neonates [4, 7,8,9,10,11,12,13]. In Japan, solid dosage forms are mainly administered as oral dosage forms, which reduces the amounts of sweeteners, dissolving agents, and preservative agents required compared to liquid dosage forms; the frequency of neonatal exposure to excipients may be assumed to be different [17,18,19]. A single-center observational study was previously conducted in Japan [20]; a nationwide investigation of excipient use in neonatal medications has not been reported. A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted
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