BACKGROUND: Repurposing broad-spectrum antivirals is an immediate treatment 
opportunity for 2019 coronavirus disease (COVID-19). Favipiravir is an antiviral 
previously indicated for influenza and Ebola, which has shown some promise in 
early trials for treatment of COVID-19. We aim to review existing favipiravir 
safety evidence, which is vital to informing the potential future use of 
favipiravir in COVID-19.
METHODS: A search was conducted across EMBASE and MEDLINE databases, 
supplemented by relevant grey-literature and ClinicalTrials.gov. All studies 
assessing the use of favipiravir in humans by 27 March 2020 were considered for 
inclusion. Further analysis of available safety data from phase 2 and 3 studies 
was undertaken. Data extracted were adverse events (AEs) grade 1-4, serious AEs 
and discontinuation for AEs. Specific AEs of interest highlighted in early-phase 
studies, including gastrointestinal AEs and hyperuricaemia, were also examined.
RESULTS: Twenty-nine studies were identified as potential sources of evidence of 
the clinical safety of favipiravir. Six were phase 2 and 3 studies reporting 
relevant safety data for statistical comparison, representing a total of 4299 
participants, an estimated 175 person-years-of-follow-up (PYFU). Comparator 
drugs were oseltamivir, umifenovir, lopinavir/ritonavir or placebo. Study 
follow-up was between 5 and 21 days. The proportions of grade 1-4 AEs on 
favipiravir was 28.2% vs 28.4% (P = n.s.) in the comparison arms. The proportion 
of discontinuations due to AEs on favipiravir was 1.1% vs 1.2% (P = n.s.) in the 
comparison arms. For serious AEs the proportion was 0.4% in both arms 
(P = n.s.). There were significantly fewer gastrointestinal AEs occurring on 
favipiravir vs comparators [8.7% vs 11.5%; P = 0.003]. Favipiravir showed 
significantly more uric acid elevations than comparators [5.8% vs 1.3%; 
P<0.0001].
CONCLUSIONS: Favipiravir demonstrates a favourable safety profile regarding 
total and serious AEs. However, safety concerns remain: hyperuricaemia, 
teratogenicity and QTc prolongation have not yet been adequately studied. 
Favipiravir may be safe and tolerable in short-term use, but more evidence is 
needed to assess the longer-term effects of treatment. Given the limitations of 
the evidence and unresolved safety concerns, caution is warranted in the 
widespread use of favipiravir against pandemic COVID-19.