Key messages
Due to a lack of robust evidence, we are unclear if favipiravir provides any benefit in the treatment of people with coronavirus disease 2019 (COVID-19) infections who do not require hospital admission, as well as those admitted to hospital.
Favipiravir might lead to mild side effects, but doesn't seem to cause major or severe side effects.
What is favipiravir?
Favipiravir is a medicine that can fight viruses. It is usually taken by mouth. Originally used for treating other viral infections, favipiravir has been suggested as a potential treatment for COVID-19 as it prevents the reproduction of the virus. Medical regulators have approved favipiravir for emergency use to treat people with COVID-19.
What did we want to find out?
We wanted to find out if favipiravir was better than no treatment, supportive treatment, or any other experimental antiviral treatment for people with COVID-19, in terms of death, need for a breathing machine (mechanical ventilation), and other outcomes. We also wanted to find out if favipiravir was associated with any unwanted effects.
What did we do?
We searched for studies that compared favipiravir with no treatment, supportive treatment, or other antiviral treatment in people with COVID-19 disease. We compared and summarized the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found 25 relevant studies involving 5750 people. The studies were conducted in 13 different countries: Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most people were under 60 years old and had mild to moderate COVID-19 symptoms.
What are the main results of our review?
• We do not know if favipiravir reduces the number of people who die from COVID-19 when compared to dummy treatment, standard of care, or other antiviral medicines. The evidence supporting this is not very strong (derived from 11 studies involving 3459 people).
• It is also very unclear if favipiravir reduces the need for people to be put on ventilators compared to a dummy treatment or any other antiviral treatments (derived from 8 studies involving 1383 people).
• In people with mild symptoms, using favipiravir may not reduce the likelihood of needing hospitalization, but more research is needed to be sure (derived from 4 studies involving 670 people).
• Favipiravir has an unclear effect on the time it takes for people to improve, as defined by a reduction in their illness severity (derived from 4 studies involving 721 people).
• Favipiravir seems to make very little difference in reducing the need for treatment with oxygen, compared to a dummy treatment or other antiviral treatment (derived from 2 studies involving 543 people).
• Favipiravir might lead to mild side effects (derived from 18 studies involving 4699 people) but doesn't seem to cause major or severe side effects (derived from 12 studies involving 3317 people).
What are the limitations of the evidence?
Our confidence in the evidence for using favipiravir is limited because people in the studies had different disease severities and the studies were of varying sizes and had inconsistent results.
How up to date is the review?
The review considered evidence up to 18 July 2023.
The 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.
The 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.
To assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19.
We 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.
We searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19.
We used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome.
We 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).