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

Journal of Pharmaceutical Health Care and Sciences

Masahiko Nakao¹  Rina Kishi²  Mayumi Torimoto²  Masaki Wada³  Hitomi Takahashi⁴  Takeshi Enokihara⁵  Naoko Akiyama⁶  Hiroaki Nagai⁷  Mami Obara⁸  Kumiko Fushimi⁹  Tomoya Takeda⁹  Toshihiro Yokoyama^1,10  Naoki Mitsuya^1,11  Makoto Setoguchi^1,12  Mari Hashimoto^1,13  Naoko Fujiwara^1,13  Kazuhiro Yamamoto^1,13  Keiko Kobayashi^1,14  Jumpei Saito^1,15  Ayano Tanzawa^1,15  Akimasa Yamatani^1,15  Rie Kihara^1,16  Hiroki Katsu^1,17  Mei Suenaga^1,18  Wakako Sakata^1,19  Hitomi Kimura^2,20  Mayuri Sameshima^2,20  Kanako Iino^2,21  Sayaka Katayama^2,22  Yuta Takahashi^2,22  Naomi Nadatani^2,23  Ran Watanabe^2,24  Kinuko Imai^2,24  Yukihiro Hamada^2,25  Toshimi Kimura^2,25  Yuki Hasegawa^2,25  Naoki Yoshikawa^2,26  Mariko Araki^2,27  Hiroaki Matsumoto^2,28 

[1] Department of Clinical Research Center, Osaka City General Hospital, Osaka-shi, Osaka, Japan;Department of Hospital Pharmacy, Nagoya University Hospital, Nagoya-shi, Aichi, Japan;Department of Neonatology, Maternal and Perinatal Center, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan;Department of Pharmacy, Anjo Kosei Hospital, Anjo-shi, Aichi, Japan;Department of Pharmacy, Dokkyo Medical University Hospital, Mibu-shi, Tochigi, Japan;Department of Pharmacy, Hospital of the University of Occupational and Environmental Health, Kitakyushu-shi, Fukuoka, Japan;Department of Pharmacy, Hyogo Prefectural, Amagasaki General Medical Center, Amagasaki-shi, Hyogo, Japan;Department of Pharmacy, Iwate Medical University, Morioka-shi, Iwate, Japan;Department of Pharmacy, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto-shi, Kyoto, Japan;Department of Pharmacy, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya-shi, Aichi, Japan;Department of Pharmacy, Japanese Red Cross Otsu Hospital, Otsu-shi, Shiga, Japan;Department of Pharmacy, Kagoshima City Hospital, Kagoshima-shi, Kagoshima, Japan;Department of Pharmacy, Kobe University Hospital, Kobe-shi, Hyogo, Japan;Department of Pharmacy, Nagano Children’s Hospital, Azumino-shi, Nagano, Japan;Department of Pharmacy, National Center for Child Health and Development, 2-10-1 Okura, 175-8535, Setagaya-ku, Tokyo, Japan;Department of Pharmacy, National Hospital Organization Kyushu Medical Center, Fukuoka-shi, Fukuoka, Japan;Department of Pharmacy, National Hospital Organization Mie Chuo Medical Center, Tsu-shi, Mie, Japan;Department of Pharmacy, National Hospital Organization Saga National Hospital, Saga-shi, Saga, Japan;Department of Pharmacy, Nihon University Itabashi Hospital, Itabashi-ku, Tokyo, Japan;Department of Pharmacy, Osaka City General Hospital, Osaka-shi, Osaka, Japan;Department of Pharmacy, Osaka Women’s and Children’s Hospital, Izumi-shi, Osaka, Japan;Department of Pharmacy, Saitama Children’s Medical Center, Saitama-shi, Saitama, Japan;Department of Pharmacy, Saitama Medical Center, Kawagoe-shi, Saitama, Japan;Department of Pharmacy, Teikyo University Hospital, Itabashi-ku, Tokyo, Japan;Department of Pharmacy, Tokyo Women’s Medical University Hospital, Shinjuku-ku, Tokyo, Japan;Department of Pharmacy, University of Miyazaki Hospital, Miyazaki-shi, Miyazaki, Japan;Division of Pharmacy, Niigata University Medical and Dental Hospital, Niigata-shi, Niigata, Japan;Division of Pharmacy, Ohara HealthCare Foundation Kurashiki Central Hospital, Kurashiki-shi, Okayama, Japan;

关键词: Excipient;    Neonate;    Enteral;    Parenteral;    Topical;    Comparative study;   

DOI  :  10.1186/s40780-021-00208-9

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY