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Role of favipiravir in the treatment of COVID-19.

ABSTRACT: The coronavirus disease-2019 (COVID-19) outbreak all over the world has led the researchers to strive to develop drugs or vaccines to prevent or halt the progression of this ailment. To hasten the treatment process, repurposed drugs are being evaluated. Favipiravir is one such oral drug that was approved for new and reemerging pandemic influenza in Japan in 2014 and has shown potent in vitro activity against severe acute respiratory syndrome coronavirus-2. It has a wide therapeutic safety margin indicated by a wide CC50/EC50 ratio for a high dose. From the clinical studies in COVID-19, it has shown rapid viral clearance as compared to lopinavir/ritonavir (LPV/RTV) and superior recovery rate than umifenovir. Overall, favipiravir has shown promising results in clinical studies in China, Russia, and Japan, and more trials are underway in multiple countries, including USA, UK, and India. Recently, treatment guidelines from many countries and some states from India have included favipiravir in the treatment protocol. This review provides insights into the evidence-based evolving role of favipiravir in the management of COVID-19 infection with emphasis on benefits of initiating an early antiviral therapy with special focus on favipiravir, its pharmacodynamic, pharmacokinetic, in vitro, clinical data, and inclusion in the treatment protocols of COVID-19.

SUBMITTER: Joshi S

PROVIDER: S-EPMC7831863 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Role of favipiravir in the treatment of COVID-19.

Joshi Shashank S Parkar Jalil J Ansari Abdul A Vora Agam A Talwar Deepak D Tiwaskar Mangesh M Patil Saiprasad S Barkate Hanmant H

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 20201030

The coronavirus disease-2019 (COVID-19) outbreak all over the world has led the researchers to strive to develop drugs or vaccines to prevent or halt the progression of this ailment. To hasten the treatment process, repurposed drugs are being evaluated. Favipiravir is one such oral drug that was approved for new and reemerging pandemic influenza in Japan in 2014 and has shown potent in vitro activity against severe acute respiratory syndrome coronavirus-2. It has a wide therapeutic safety margin ...[more]

PMID: 33130203

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Project description:BackgroundThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and societies worldwide. Favipiravir was suggested by some experts to be effective and safe to use in COVID-19. Although this drug has been evaluated in randomized controlled trials (RCTs), it is still unclear if it has a definite role in the treatment of COVID-19.ObjectivesTo assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19.Search methodsWe searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, and three other databases, up to 18 July 2023.Selection criteriaWe searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19.Data collection and analysisWe used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome.Main resultsWe included 25 trials that randomized 5750 adults (most under 60 years of age). The trials were conducted in Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most participants were hospitalized with mild to moderate disease (89%). Twenty-two of the 25 trials investigated the role of favipiravir compared to placebo or standard of care, whilst lopinavir/ritonavir was the comparator in two trials, and umifenovir in one trial. Most trials (24 of 25) initiated favipiravir at 1600 mg or 1800 mg twice daily for the first day, followed by 600 mg to 800 mg twice a day. The duration of treatment varied from five to 14 days. We do not know whether favipiravir reduces all-cause mortality at 28 to 30 days, or in-hospital (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.46; 11 trials, 3459 participants; very low-certainty evidence). We do not know if favipiravir reduces the progression to invasive mechanical ventilation (RR 0.86, 95% CI 0.68 to 1.09; 8 trials, 1383 participants; very low-certainty evidence). Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory) (RR 1.04, 95% CI 0.44 to 2.46; 4 trials, 670 participants; low-certainty evidence). We do not know if favipiravir reduces the time to clinical improvement (defined as time to a 2-point reduction in patients' admission status on the WHO's ordinal scale) (hazard ratio (HR) 1.13, 95% CI 0.69 to 1.83; 4 trials, 721 participants; very low-certainty evidence). Favipiravir may make little to no difference to the progression to oxygen therapy (RR 1.20, 95% CI 0.83 to 1.75; 2 trials, 543 participants; low-certainty evidence). Favipiravir may lead to an overall increased incidence of adverse events (RR 1.27, 95% CI 1.05 to 1.54; 18 trials, 4699 participants; low-certainty evidence), but may result in little to no difference inserious adverse eventsattributable to the drug (RR 1.04, 95% CI 0.76 to 1.42; 12 trials, 3317 participants; low-certainty evidence).Authors' conclusionsThe low- to very low-certainty evidence means that we do not know whether favipiravir is efficacious in people with COVID-19 illness, irrespective of severity or admission status. Treatment with favipiravir may result in an overall increase in the incidence of adverse events but may not result in serious adverse events.

Project description:BackgroundFavipiravir possesses high utility for treating patients with COVID-19. However, research examining the efficacy and safety of favipiravir for patients with COVID-19 is limited.MethodsWe conducted a systematic review of published studies reporting the efficacy of favipiravir against COVID-19. Two investigators independently searched PubMed, the Cochrane Database of Systematic Reviews, MedRxiv, and ClinicalTrials.gov (inception to September 2020) to identify eligible studies. A meta-analysis was performed to measure viral clearance and clinical improvement as the primary outcomes.ResultsAmong 11 eligible studies, 5 included a comparator group. Comparing to the comparator group, the favipiravir group exhibited significantly better viral clearance on day 7 after the initiation of treatment (odds ratio [OR] = 2.49, 95% confidence interval [CI] = 1.19-5.22), whereas no difference was noted on day 14 (OR = 2.19, 95% CI = 0.69-6.95). Although clinical improvement was significantly better in the favipiravir group on both days 7 and 14, the improvement was better on day 14 (OR = 3.03, 95% CI = 1.17-7.80) than on day 7 (OR = 1.60, 95% CI = 1.03-2.49). The estimated proportions of patients with viral clearance in the favipiravir arm on days 7 and 14 were 65.42 and 88.9%, respectively, versus 43.42 and 78.79%, respectively, in the comparator group. The estimated proportions of patients with clinical improvement on days 7 and 14 in the favipiravir group were 54.33 and 84.63%, respectively, compared with 34.40 and 65.77%, respectively, in the comparator group.ConclusionsFavipiravir induces viral clearance by 7 days and contributes to clinical improvement within 14 days. The results indicated that favipiravir has strong possibility for treating COVID-19, especially in patients with mild-to-moderate illness. Additional well-designed studies, including examinations of the dose and duration of treatment, are crucial for reaching definitive conclusions.

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Role of favipiravir in the treatment of COVID-19.

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Role of favipiravir in the treatment of COVID-19.

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