Syringe-dispensed omega-3 lipid injectable emulsions should be stored under airtight refrigeration: A proposal for the efficient supply of unapproved precious lipid resources.

BACKGROUND: Both fish-oil lipid injectable emulsion (FO-ILE) and mixed-oil lipid injectable emulsion (MO-ILE) are key components of parenteral nutrition and require importation into Japan, and they are easily oxidized after opening. Given the small daily volumes of these lipids dispensed in infants and children with intestinal failure (IF), the purpose of the study was to identify the optimal storage method. METHODS: Lipids were prepared in polypropylene syringes in the following manner: air-sealing and photoprotection, air-sealing only, photoprotection only, and uncovered. Samples were stored for 14 days at 4°C or 26°C. The degree of oxidative degradation was evaluated by measuring malondialdehyde (MDA) concentration and pH and comparing them to the values measured immediately after opening. RESULTS: For FO-ILE, the increase in MDA concentration for 14 days was insignificant in air-sealed samples, regardless of photoprotection (+0.45 µM, P = 1.0) or no photoprotection (+0.52 µM, P = 1.0). This trend was more pronounced at 4°C than at 26°C (P < 0.01). The maximum pH decrease was 0.08 at 4°C. MO-ILE exhibited an insignificant increase in MDA concentration for 14 days with air-sealed samples, regardless of photoprotection (+0.36 µM, P = 0.11) or no photoprotection (+0.33 µM, P = 0.76). This trend was more pronounced at 4°C than at 26°C (P < 0.01). The maximum pH decrease was 0.12 at 4°C. For soybean-oil lipid injectable emulsion, the trend was similar with no considerable deterioration. CONCLUSION: Syringe-dispensed FO-ILE and MO-ILE stored under airtight refrigeration remained undeteriorated for 14 days. Our results are considered clinically valuable when supplying these expensive resources for infants with IF.

Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan.

BACKGROUND: A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted. METHODS: A 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. RESULTS: Prescription 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. CONCLUSIONS: Neonates 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.