Consequence of Antivirals Versus Standard Care on Clinical Situation in Patients With COVID-19
et al., Infectious Diseases in Clinical Practice, doi:10.1097/IPC.0000000000001336, Jan 2024
RCT 156 COVID-19 patients showing higher mortality with favipiravir and remdesivir overall. Favipiravir and remdesivir were more effective when started earlier, however note that Table 10 compares earlier favipiravir/remdesivir+standard care with standard care at any time, which will exaggerate the benefits/harms of earlier/later treatment. The confidence intervals for the Cox results are unusually narrow suggesting a possible error in calculation.
Potential risks of favipiravir include kidney injury1-3, liver injury2-4, and mutagenicity, carcinogenicity, teratogenicity, embryotoxicity, and the creation of dangerous variants5-11.
This study is excluded in the after exclusion results of meta
analysis:
potential data issue.
Study covers remdesivir and favipiravir.
|
risk of death, 87.1% higher, HR 1.87, p = 0.26, treatment 9 of 51 (17.6%), control 5 of 53 (9.4%), adjusted per study, multivariable, Cox proportional hazards, day 30.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
1.
Abdulaziz et al., Clinical Features and Prognosis of Acute Kidney Injury in Hospital-Admitted Patients with COVID-19 in Egypt: A Single-Center Experience, Mansoura Medical Journal, doi:10.58775/2735-3990.1433.
2.
Ülger et al., Experimental evaluation of favipiravir (T-705)-induced liver and kidney toxicity in rats, Food and Chemical Toxicology, doi:10.1016/j.fct.2025.115472.
3.
El-Fetouh et al., Experimental Studies on Some Drugs Used in Covid-19 Treatment (Favipiravir and Dexamethasone) in Albino Rats, Journal of Advanced Veterinary Research, 13:10, www.advetresearch.com/index.php/AVR/article/view/1635.
4.
Almutairi et al., Liver Injury in Favipiravir-Treated COVID-19 Patients: Retrospective Single-Center Cohort Study, Tropical Medicine and Infectious Disease, doi:10.3390/tropicalmed8020129.
5.
Zhirnov et al., Favipiravir: the hidden threat of mutagenic action, Journal of microbiology, epidemiology and immunobiology, doi:10.36233/0372-9311-114.
6.
Waters et al., Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environmental and Molecular Mutagenesis, doi:10.1002/em.22471.
7.
Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.
8.
Shum, C., An investigational study into the drug-associated mutational signature in SARS-CoV-2 viruses, The University of Hong Kong, PhD Thesis, hub.hku.hk/handle/10722/344396.
9.
Shiraki et al., Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans, Heliyon, doi:10.1016/j.heliyon.2024.e35331.
Alsaraj et al., 8 Jan 2024, Randomized Controlled Trial, Iraq, peer-reviewed, 6 authors, study period September 2021 - February 2022.
Contact: m.n.abed@uomosul.edu.iq.
Consequence of Antivirals Versus Standard Care on Clinical Situation in Patients With COVID-19
Favipiravir and remdesivir have recently received more clinical interest for the management of COVID-19. The study aimed to explore the effectiveness of favipiravir or remdesivir on the clinical outcome of SARS-CoV-2 patients in comparison with standard care. All patients were given standard care before being randomized into the following 3 groups: standard care group (standard care only), remdesivir group (remdesivir and standard care), and favipiravir group (group 3, favipiravir and standard care). The primary endpoint of the study was time to recovery or the clinical condition of patients on day 14. A total of 156 patients underwent randomization (53 assigned to standard care group, 51 to favipiravir group, and 52 to remdesivir group). The percentage of death in favipiravir and remdesivir groups was higher than those in the standard care group and likewise the liver enzymes. Studying the time to starting therapy showed that early administration of antivirals resulted in lower percentage of mortality. The ratio of hazard for early favipiravir and remdesivir was lower in comparison with those treated with late administration of the same drugs (hazard ratio, 0.62; 95% confidence interval [CI], 0.62-0.73 vs 3.22; 95% CI, 3.21-3.44, respectively, for favipiravir and 0.11; 95% CI, 0.10-0.12 vs 3.44; 95% CI, 3.43-3.55, respectively, for remdesivir). For favipiravir or remdesivir to have more beneficial effects than standard care alone for SARS-CoV-2 patients, they need to be started as early as possible. However, regular monitoring of liver function is required.
References
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Shannon, Selisko, Le, Rapid incorporation of favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis, Nat Commun
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Williamson, Feldmann, Schwarz, Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2, Nature
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:p>Favipiravir and remdesivir have recently received more clinical interest for the management of COVID-19. The study aimed to explore the effectiveness of favipiravir or remdesivir on the clinical outcome of SARS-CoV-2 patients in comparison with standard care. All patients were given standard care before being randomized into the following 3 groups: standard care group (standard care only), remdesivir group (remdesivir and standard care), and favipiravir group (group 3, favipiravir and standard care). The primary endpoint of the study was time to recovery or the clinical condition of patients on day 14. A total of 156 patients underwent randomization (53 assigned to standard care group, 51 to favipiravir group, and 52 to remdesivir group). The percentage of death in favipiravir and remdesivir groups was higher than those in the standard care group and likewise the liver enzymes. Studying the time to starting therapy showed that early administration of antivirals resulted in lower percentage of mortality. The ratio of hazard for early favipiravir and remdesivir was lower in comparison with those treated with late administration of the same drugs (hazard ratio, 0.62; 95% confidence interval [CI], 0.62–0.73 vs 3.22; 95% CI, 3.21–3.44, respectively, for favipiravir and 0.11; 95% CI, 0.10–0.12 vs 3.44; 95% CI, 3.43–3.55, respectively, for remdesivir). For favipiravir or remdesivir to have more beneficial effects than standard care alone for SARS-CoV-2 patients, they need to be started as early as possible. However, regular monitoring of liver function is required.</jats:p>",
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