-Original-

Physical Compatibility of Nafamostat with Analgesics, Sedatives, and Muscle Relaxants for Treatment of Coronavirus Disease 2019

Masayoshi Kondo, Makihiko Nagano, Mariko Yoshida, Naoki Yoshida, Naoya Tagui, Masato Yoshida, Kazutoshi Sugaya and Hisamitsu Takase

Department of Pharmacy, Nippon Medical School Tama Nagayama Hospital, Tokyo, Japan

Background: Severe coronavirus disease 2019 (COVID-19) may require continuous administration of analgesics, sedatives, and muscle relaxants. Nafamostat has recently been reported as a therapeutic agent for COVID-19. However, there is a lack of information on the compatibility of nafamostat with the aforementioned drug classes. This study evaluated the physical compatibility of nafamostat with these drug classes.
Methods: Nafamostat was combined with 1-3 target drugs (fentanyl, morphine, midazolam, dexmedetomidine, and rocuronium). Fifteen physical compatibility tests were conducted. Nafamostat was dissolved in 5% glucose solution; the final concentration was 10 mg/mL. All other medications were diluted in 0.9% sodium chloride to obtain clinically relevant concentrations. The power of hydrogen (pH) of all medications was measured during each test. Compatibility tests were conducted with 4 test solutions in which nafamostat and the target drugs were compounded at equal volume ratios (1:1, 1:1:1, or 1:1:1:1). Visual appearance, turbidity, and pH were evaluated immediately after mixing and at 1 and 3 hours. Physical incompatibilities were defined as gross precipitation, cloudiness, appearance of the Tyndall effect, or a turbidity change of ≥0.5 nephelometric turbidity units (NTU) based on nafamostat.
Results: The mean pH of nafamostat was 3.13 ± 0.03. The combination of nafamostat, fentanyl, and dexmedetomidine had the highest pH (3.39 ± 0.01; 3 hours after mixing). All drugs were compatible with nafamostat until 3 hours after admixture, with a mean turbidity value of ≤0.03 NTU.
Conclusions: Infusions combining nafamostat with the tested sedatives, analgesics, and muscle relaxants could be safely administered.

J Nippon Med Sch 2021; 88: 533-539

Keywords
coronavirus disease (COVID-19), nafamostat, compatibility, drug administration route, power of hydrogen (pH)

Correspondence to
Masayoshi Kondo, Department of Pharmacy, Nippon Medical School Tama Nagayama Hospital, 1-7-1 Nagayama, Tama, Tokyo 206-8512, Japan
kondomasayoshi@nms.ac.jp

Received, October 4, 2020
Accepted, February 3, 2021