Home | DEU |ENG | ESP | FRA | ITA | POR | TUR | VNM

3 May 2020

Remdesivir (abbreviation: RDV) is a monophosphoramidate prodrug of an adenosine analog with potent activity against an array of single stranded RNA virus families including Filoviridae, Paramyxoviridae, Pneumoviridae, and Orthocoronavirinae (Brown 2019, Sheehan 2017), through the targeting of the viral RNA dependent RNA polymerase (RdRp) (Cho 2012, Agostini 2018). The drug was initially reported to have in vivo antiviral efficacy against Ebola virus in nonhuman primates (Warren 2016) and it was used during the Kivu Ebola epidemic. However, a randomized controlled trial showed that remdesivir was significantly less effective than the single monoclonal antibody mAb114, or the triple monoclonal antibody REGN-EB3 (Mulangu 2019).

The first remdesivir COVID-19 studies showed mixed results. Findings of a compassionate use program (Grein 2020) have been judged inconclusive and are being interpreted with caution. Results of the first randomised, double-blind, placebo-controlled, multicenter trial reported that RDV use was not associated with a difference in time to clinical improvement (Wang Y 2020). Only patients who received the drug within the first 10 days after the appearance of symptoms seemed to have a faster time to clinical improvement; however, this was statistically not significant.

On 1 May 2020, the FDA granted RDV emergency use authorization for treatment of COVID-19. The drug will still need formal approval if the manufacturer provides additional data of the drug’s safety and effectiveness.

Although remdesivir is far from being a penicillin-like watershed in medicine, some studies indicate that SARS-2-CoV could be amenable to drug treatment. More potent drugs are urgently needed.

Brand Name: N/A™

Drug Class: Nucleotide Analog

Manufacturer: Gilead Sciences

N/A™ vials: 100 mg.

Remdesivir can be administered only by intravenous injection.

Indications: COVID-19.

Dose used during trials: Loading dose of 200 mg IV on day 1, followed by 100 mg IV daily for 9 days (Wang Y 2020).

Side effects: Typical side effects include nausea and vomiting, elevated transaminases and infusion site reactions (Mehta 2020). Signs and symptoms of infusion‐related reactions may include low blood pressure, nausea, vomiting, sweating and shivering (FDA 2020).

Interactions: RDV is not believed to affect other medications; however, some drugs may affect RDV and should probably not be coadministered: rifampicin, rifapentine, carbamazepine, phenobarbital, phenytoin, primidone, St John’s wort may affect RDV. For more details, consult information provided by the Liverpool Drug Interactions Group at www.covid19-druginteractions.org.

Comments/Warnings: It is unknown whether RDV is safe during pregnancy and whether it passes into breast milk.

References

Agostini ML, Andres EL, Sims AC, et al. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018 Mar 6;9(2). pii: mBio.00221-18. PubMed: https://pubmed.gov/29511076. Full-text: https://doi.org/10.1128/mBio.00221-18

Brown AJ, Won JJ, Graham RL, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res. 2019 Sep;169:104541. PubMed: https://pubmed.gov/31233808. Full-text: https://doi.org/10.1016/j.antiviral.2019.104541

Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med. 2020 Apr 10. PubMed: https://pubmed.gov/32275812. Full-text: https://doi.org/10.1056/NEJMoa2007016

FDA. Frequently Asked Questions on the Emergency Use Authorization for Remdesivir for Certain Hospitalized COVID‐19 Patients”. U.S. Food and Drug Administration (FDA). 1 May 2020. https://www.fda.gov/media/137574/download. Retrieved 3 May 2020.

Mehta N, Mazer-Amirshahi M, Alkindi N, Ali Pourmand. Pharmacotherapy in COVID-19; A narrative review for emergency providers. Am J Emerg Med. 2020 Apr 15. pii: S0735-6757(20)30263-1. PubMed: https://pubmed.gov/32336586. Full-text: https://doi.org/10.1016/j.ajem.2020.04.035

Mulangu S, Dodd LE, Davey RT Jr, et al. A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. N Engl J Med. 2019 Dec 12;381(24):2293-2303. PubMed: https://pubmed.gov/31774950. Full-text: https://doi.org/10.1056/NEJMoa1910993

Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017 Jun 28;9(396). pii: 9/396/eaal3653. PubMed: https://pubmed.gov/28659436. Full-text: https://doi.org/10.1126/scitranslmed.aal3653

Warren TK, Jordan R, Lo MK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016 Mar 17;531(7594):381-5. PubMed: https://pubmed.gov/26934220. Full-text: https://doi.org/10.1038/nature17180

Cho A, Saunders OL, Butler T, et al. Synthesis and antiviral activity of a series of 1´-substituted 4-aza-7,9-dideazaadenosine C-nucleosides. Bioorg Med Chem Lett. 2012 Apr 15;22(8):2705-7. PubMed: https://pubmed.gov/22446091. Full-text: https://doi.org/10.1016/j.bmcl.2012.02.105

Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet, April 29, 2020. Full-text: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext