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| REVIEW ARTICLE |
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| Year : 2020 | Volume
: 2
| Issue : 2 | Page : 51-54 |
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Remdesivir and Favipiravir for COVID-19: An update
Suman Omana Soman1, AV Raveendran2
1 Department of Cardiology, Badr Al Samaa Hospital, Muscat, Oman
2 Department of Medicine, Badr Al Samaa Hospital, Muscat, Oman
| Date of Submission | 02-Aug-2020 |
| Date of Decision | 02-Aug-2020 |
| Date of Acceptance | 25-Aug-2020 |
| Date of Web Publication | 07-Oct-2020 |
Correspondence Address:
Dr. Suman Omana Soman
Simi Bhavan, Azhoor.P.O, Perumguzhi, Trivandrum
Oman
 Source of Support: None, Conflict of Interest: None  | 2 |
DOI: 10.4103/2666-6979.297511
COVID-19 pandemic due to SARS-CoV-2 infection has already resulted in more than 6 lakhs death worldwide. Various drugs like hydroxychloroquine, lopinavir/ritonavir, dexamethasone, ivermectin etc are examples of drugs currently used to treat COVID-19 with varying results. Remdesivir is a broad spectrum anti-viral agent, which is active against Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-1, Ebola virus etc. Favipiravir had been widely used for treating influenza pandemics in Japan in 2014 .Studies showed that it was effective for treating many RNA viruses like arenavirus, bunyavirus, flavivirus, and filoviruses causing hemorrhagic fever and Ebola virus. Remdesivir and favipiravir are anti-viral agents tried in patients with COVID-19 with varying results. Currently Remdesivir is recommended in hospitalized patients with COVID-19 requiring supplemental oxygen and favipiravir in patients with mild to moderate disease. In this article we are reviewing the pharmacological features and clinical use of Remdesivir and favipiravir in COVID-19.
Keywords: COVID-19, favipiravir, remdesivir
How to cite this article:
Soman SO, Raveendran A V. Remdesivir and Favipiravir for COVID-19: An update. Ann Clin Cardiol 2020;2:51-4 |
| Introduction | |  |
COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has already resulted in more than 6 lakhs death worldwide. The search for an effective anti-viral agent and vaccines to control the disease is a prime issue in front of the health professionals and researchers. The development of new drugs or repurposing of available agents is the option available. Various drugs such as hydroxychloroquine (HCQS), lopinavir/ritonavir, dexamethasone, ivermectinetc are examples of drugs currently used to treat COVID-19 with varying results. Remdesivir is a broad-spectrum antiviral agent, which is active against the Middle East respiratory syndrome CoV, SARS-CoV-1, Ebola virus, Nipah virus, and respiratory syncytial virus.[1],[2],[3] Favipiravir had been widely used for treating influenza pandemics in Japan in 2014.[4] Studies showed that it was effective for treating many RNA viruses such as arenavirus, flavivirus, bunyavirus, and filoviruses, causing hemorrhagic fever and Ebola virus.[5],[6],[7] It is tried in patients with COVID-19 and is in this article, we are reviewing the pharmacological features and clinical use of remdesivir and favipiravir in COVID-19.
| Remdesivir | | |
Remdesivir, an adenosine nucleotide prodrug, is found to be effective in SARS-CoV-2 infection.
| Mechanism of Action | | |
Remdesivir is an adenosine nucleotide prodrug. After entering into the cells, it is metabolized into pharmacologically active nucleoside triphosphate metabolite. Remdesivir triphosphate acts as an adenosine triphosphate analog and it competes for RNA chain incorporation by the SARS-CoV-2 RNA-dependent RNA polymerase. Incorporation of remdesivir triphosphate into the nascent RNA chain inhibits viral replication by inducing delayed termination of RNA chain [8] [Figure 1].
| Indication in COVID-19 | | |
Remdesivir is indicated for “compassionate use” in hospitalized patients with COVID-19 who require supplemental oxygen but who are not on high-flow oxygen, noninvasive ventilation, extracorporeal membrane oxygenation, or mechanical ventilation.[9]
| Dose Recommendation | | |
The recommended dose of remdesivir is 200 mg intravenous (IV) infused over 30–120 min on day 1, followed by maintenance dose of 100 mg IV once daily for days 2–5. The duration of treatment is usually 5 days. Those who do not improve after 5 days of receiving remdesivir consider extending the total treatment duration to up to 10 days.[10]
| Dose Adjustment of Remdesivir in Renal and Hepatic Dysfunction | | |
The dose adjustment in patients with renal impairment is given in [Table 1]. In patients with renal impairment if the estimated glomerular filtration rate (eGFR) falls to >50% from baseline, it has to be discontinued.[11]
Remdesivir not to be used in patients with baseline alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN). If, during treatment, ALT increases ≥5 times the ULN, it has to be discontinued till ALT becomes <5 times the ULN.[11] Associated with ALT elevation if there are signs or symptoms of liver inflammation or increasing levels of conjugated bilirubin, alkaline phosphatase, or international normalized ratio, discontinue remdesivir.
| In Pregnancy | | |
The safety of remdesivir during pregnancy and lactation is not known. During the Ebola virus infection, significant number of pregnant ladies received remdesivir without much issue.[12]
| Adverse Effects | | |
Remdesivir can cause transaminase elevations, hence advised to perform liver function tests at baseline and daily during remdesivir administration. During intravenous administration, infusion-related reactions can occur. These include diaphoresis, nausea and vomiting, hypotension, and shivering. Other adverse effects include phlebitis, headache, ecchymosis, transient increase in prothrombin time, and blood sugar.[11]
| Drug Interaction | | |
Remdesivir should not be combined with chloroquine and HCQS, as this may diminish the anti-viral effect of remdesivir.
| Monitoring Parameters | | |
During treatment with remdesivir look for features of the infusion reaction and manage accordingly. Obtain baseline and daily liver function tests; hematology; renal function tests and serum chemistries.
| Clinical Evidence | | |
There are case series suggesting beneficial effects of remdesivir. In one study, treatment with remdesivir is associated with 68% clinical improvement in severe cases and 100% and 71% improvement with mild and moderate disease, respectively.[13] Another randomized controlled trial (RCT) showed that remdesivir treatment is associated with 31% faster time to recovery.[14] It is also showed that the results are better if remdesivir is started early in the course of illness, within 10 days of illness.[15] Another trial of patients with severe COVID-19 showed that remdesivir treatment duration of 5 days and 10 days had similar clinical benefit.[16] Another RCT showed no improvement, and it adds to the confusion regarding the clinical benefits of remdesivir in COVID-19.[17]
| Favipiravir | | |
Favipiravir, a pyrazinecarboxamide derivative prodrug, is also used to treat COVID-19.
| Mechanism of Action | | |
Favipiravir is a pyrazinecarboxamide derivative prodrug, which isribosylated and phosphorylated inside the cell and forms favipiravir ibofuranosyl-5′-triphosphate, which is an active metabolite. It inhibits the enzyme RNA-dependent RNA polymerase (RdRp inhibitor) of RNA virus and it prevents elongation and proliferation of viral genome [Figure 2].[18],[19]
| Indication in COVID-19 | | |
Favipiravir is indicated for mild-to-moderate COVID-19 patients.
| Dose Recommendation | | |
The estimated half-life of favipiravir is around 2–5.5 h.[20] It undergoes hydroxylation primarily by aldehyde oxidase and by xanthine oxidase. Favipiravir can start with an initial dose of 1600 mg twice a day, followed by 600 mg twice for a period of 7–10 days.[21]
| Dose Adjustment of Favipiravir in Renal and Hepatic Dysfunction | | |
In people with eGFR 30–50 mL/min, the plasma level of favipiraviris was found to be about three times higher. Still, it is safe, but not preferred in people with eGFR >20 mL/min. Usually, no dose adjustment is required in renal impairment.
| In Pregnancy | | |
Favipiravir is not recommended for usage in pregnancy because of its teratogenicity.[5]
| Drug Interaction | | |
Favipiravir can cause potential drug interactions with pyrazinamide, theophylline, famciclovir, and sulindac.
| Monitoring Parameters | | |
During treatment with favipiravir, look for features of drug reaction and manage accordingly. Obtain baseline and daily liver function tests; hematology; renal function tests, uric acid, and serum chemistries.
| Clinical Evidence | | |
A randomized prospective study conducted by Chen et al. in Wuhan, China, showed that favipiravir is superior to umifenovir for treating COVID-19 patients.[22] In a nonrandomized trial by Cia et al. found that patients who received favipiravir had a faster recovery and improvement in radiological imaging compared with lopinavir/ritonavir treated COVID-19 patients.[23]
| Conclusion | | |
Remdesivir and favipiravir are anti-viral agents tried in patients with COVID-19 with varying results. Currently, remdesivir is recommended in hospitalized patients with COVID-19 requiring supplemental oxygen and favipiravir in patients with mild-to-moderate disease. The on-going trials are expected to through more light into its role in patients with COVID-19.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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| 14. | NIH clinical trial shows Remdesivir accelerates recovery from advanced COVID-19. Available from: https://www.nih.gov/news-events/news-releases/nih-clinical- trial-shows-remdesivir-accelerates-recovery-advanced- covid-19. [Last accessed on 2020 Sep 12]. |
| 15. | Gilead Announces Results From Phase 3 Trial of Investigational Antiviral Remdesivir in Patients With Severe COVID-19. |
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| 23. | Cai, Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering 2020 |
[Figure 1], [Figure 2]
[Table 1]
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