Remdesivir administration for Japanese COVID-19 patients undergoing maintenance hemodialysis: a retrospective observation with six case reports.

Background: The mortality rate of novel coronaviral disease (COVID-19) patients undergoing dialysis is considerably higher than that of patients with normal kidney function. As of August 2021, only remdesivir has been approved in Japan as an antiviral drug for the treatment of COVID-19. However, in cases of kidney failure, remdesivir administration should be considered only if the therapeutic benefits outweigh the risks because of concern about the accumulation of its solubilizing excipient sulfobutylether-beta-cyclodextrin and subsequent renal tubular injury or liver injury. Recently, reports from overseas indicating the safety of the use of remdesivir for COVID-19 patients on dialysis have been gathered. Case presentation: From June 2021, in our hospital, we started the administration of remdesivir to patients with moderate cases of COVID-19 undergoing hemodialysis, with careful consideration of the dosage and timing. Since then, six out of seven COVID-19 patients on hemodialysis who had received remdesivir have completely recovered. In a patient who died, the initial dose of remdesivir was administered after the case developed into severe COVID-19. All six patients who were able to start receiving remdesivir immediately at the stage of moderate COVID-19 recovered and were discharged without the need for mechanical ventilation. While, two out of four patients before May 2021 who had not been administered remdesivir at admission became severe, transferred to another tertiary hospital, and died. During and after remdesivir administration, no increase in serum transaminase to five times or more of the normal upper limit was observed in any of the cases. There were no other adverse drug reactions, such as infusion reaction, gastrointestinal symptoms, or anemia. Conclusions: We were able to administer remdesivir to six Japanese patients with moderate COVID-19 on hemodialysis safely. It is expected that the safe use of remdesivir will bring an increase in treatment options for moderate cases of COVID-19 in dialysis patients as well as subsequent improvement in treatment outcomes. However, to confirm the efficacy and safety of such use, further careful observation in more cases is required.

Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations.

Veklury™ by Gilead Sciences, Inc., containing antiviral drug, remdesivir (REM) has received emergency authorization in the USA and in Europe for COVID-19 therapy. Here, for the first time, we describe details of the non-covalent, host-guest type interaction between REM and the solubilizing excipient, sulfobutylether-beta-cyclodextrin (SBECD) that results in significant solubility enhancement. Complete amorphousness of the cyclodextrin-enabled REM formulation was demonstrated by X-ray diffraction, thermal analysis, Raman chemical mapping and electron microscopy/energy dispersive spectroscopy. The use of solubilizing carbohydrate resulted in a 300-fold improvement of the aqueous solubility of REM, and enhanced dissolution rate of the drug enabling the preparation of stable infusion solutions for therapy. 2D ROESY NMR spectroscopy provided information on the nature of REM-excipient interaction and indicated the presence of inclusion phenomenon and the electrostatic attraction between anionic SBECD and nitrogen-containing REM in aqueous solution.